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Objective: Although guidelines support the efficacy of Modified Qing' E Formula (MQEF) in treating postmenopausal osteoporosis (PMOP), its underlying mechanisms remain incompletely understood. This retrospective investigation aims to elucidate MQEF's impact on serum exosomal miRNA expression in postmenopausal osteoporosis patients and to explore potential therapeutic mechanisms. Methods: Following ethical approval and registration, postmenopausal osteoporosis patients aged 50-85 years, meeting the diagnostic criteria were randomly selected and received MQEF decoction supplementary therapy. Serum samples were collected pre- and post-treatment, followed by isolation and sequencing of exosomal miRNAs. Differential miRNAs in serum exosomes were identified, and bioinformatics analysis was conducted to discern the principal exosomal miRNAs involved in MQEF's effects on PMOP and the associated signaling pathways. Results: Eighteen clinical blood samples were collected. A total of 282,185 target genes were detected across the three groups. 306 miRNAs exhibited altered expression in serum exosomes of PMOP patients, while MQEF intervention resulted in changes in 328 miRNAs. GO enrichment analysis revealed the immune and endocrine systems was pertained. KEGG enrichment analysis indicated associations between PMOP occurrence and MQEF treatment with cytokine interactions, oxidative phosphorylation, and the renin-angiotensin system. Intersectional analysis identified 17 miRNAs, including 2 consistent trends. miR-3188 as a potentially pivotal miRNA implicated in both PMOP occurrence and MQEF treatment. Conclusion: This study constitutes the first randomized, retrospective clinical exploration confirming that MQEF demonstrates regulatory influence over exosomal miRNA expression in PMOP patients' serum, its impact likely involves modulation of the immune and endocrine systems, as well as the renin-angiotensin system. [ABSTRACT FROM AUTHOR]

The renin-angiotensin system (RAS) of the kidney is responsible for renal regulation and homeostasis, and patients with chronic kidney disease frequently receive RAS blockades. The purpose of this study was to determine the connection between the stimulation of arsenic in rats and changes in transcription levels of RAS hormones, biochemical parameters and antioxidant enzymes. Twenty-five Wistar rats were divided into five groups (control, low, middle, high dose and high dose + α-tocopherol groups) and given oral doses of 8.2, 12.3 and 16.4 mg/kg sodium arsenite (NaAsO2) and 50 mg/kg α-tocopherol for two months. RT-PCR analysis in nephrocytes revealed that mRNA expression of p53, p21, p27, caspases (3, 7 and 9), ACE, AGT, AT1R, CYP1A1 and Bax was found to be upregulated by ~1.9, ~1.6, ~1.5, ~2.3, ~3.3, ~3, ~2, ~1.9, ~2.4, ~1.7 and ~3.3-fold, whereas that of cyclin A, cyclin B1, cyclin E1, CDK 1, CDK 2, Bcl-2, CAT, SOD, GPx, GR and GST was downregulated consistently in renal tissues of arsenic-exposed groups by ~0.6, ~0.5, ~0.4, ~0.5, ~0.6, ~0.5, ~0.6, ~0.4, ~0.6, ~0.5 and ~0.6-fold respectively. The activities of alkaline phosphatase, acid phosphatase and antioxidant enzymes were significantly reduced by 63%, 71%, 40%, 37% and 44% respectively, upon treatment with NaAsO2. Through this study, we can gain knowledge about the potential function of RAS enzymes and antioxidant enzymes against the detrimental effects of arsenic-induced oxidative stress due to altered transcription levels of RAS enzymes in Wistar rats. [ABSTRACT FROM AUTHOR]

Nitric oxide (NO) is widely recognized for its role in regulating renal function and blood pressure. However, the precise mechanisms by which NO affects renal epithelial cells remain understudied. Our previous research has shown that NO signaling in glomerular podocytes can be initiated by Angiotensin II (ANG II) but not by ATP. This study aims to elucidate the crucial interplay between the renin-angiotensin system (RAS) and NO production in podocytes. To conduct our research, we used cultured human podocytes and freshly isolated rat glomeruli. A variety of RAS peptides were used, alongside confocal microscopy, to detect NO production and NO/Ca2+ cross talk. Dynamic changes in the podocyte cytoskeleton, mediated by RAS-NO intracellular signaling, were observed using fluorescent labeling for F-actin and scanning probe microscopy. The experiments demonstrated that ANG II and ANG III generated high levels of NO by activating the angiotensin II type 2 receptor (AT2R). We did not detect functional MAS receptor presence in podocytes, and the moderate NO response to ANG 1–7 was also mediated through AT2R. Furthermore, NO production impacted intracellular Ca2+ signaling and correlated with an increase in podocyte volume and growth. Scanning probe experiments revealed that AT2R activation and the corresponding NO generation are responsible for the protrusion of podocyte lamellipodia. Taken together, our data indicate that AT2R activation enhances NO production in podocytes and subsequently mediates changes in Ca2+ signaling and podocyte volume dynamics. These mechanisms may play a significant role in both physiological and pathophysiological interactions between the RAS and podocytes. NEW & NOTEWORTHY: The renin-angiotensin system plays a crucial role in the production of intracellular nitric oxide within podocytes. This mechanism operates through the activation of the angiotensin II type 2 receptor, leading to dynamic modifications in intracellular calcium levels and the actin filament network. This intricate process is vital for linking the activity of angiotensin receptors to podocyte function. [ABSTRACT FROM AUTHOR]

There are diverse pathophysiological mechanisms involved in acute kidney injury (AKI). Among them, overactivity of the renin-angiotensin system (RAS) has been described. Angiotensin-converting enzyme 2 (ACE2) is a tissue RAS enzyme expressed in the apical border of proximal tubules. Given the important role of ACE2 in the metabolism of angiotensin II, this study aimed to characterize kidney and urinary ACE2 in a mouse model of AKI. Ischemia-reperfusion injury (IRI) was induced in C57BL/6 mice by clamping of the left renal artery followed by removal of the right kidney. In kidneys harvested 48 h after IRI, immunostaining revealed a striking maldistribution of ACE2 including spillage into the tubular lumen and the presence of ACE2-positive luminal casts in the medulla. In cortical membranes, ACE2 protein and enzymatic activity were both markedly reduced (37 ± 4 vs. 100 ± 6 ACE2/β-actin, P = 0.0004, and 96 ± 14 vs. 152 ± 6 RFU/μg protein/h, P = 0.006). In urine, full-length membrane-bound ACE2 protein (100 kDa) was markedly increased (1,120 ± 405 vs. 100 ± 46 ACE2/µg creatinine, P = 0.04), and casts stained for ACE2 were recovered in the urine sediment. In conclusion, in AKI caused by IRI, there is a marked loss of ACE2 from the apical tubular border with deposition of ACE2-positive material in the medulla and increased urinary excretion of full-length membrane-bound ACE2 protein. The deficiency of tubular ACE2 in AKI suggests that provision of this enzyme could have therapeutic applications and that its excretion in the urine may also serve as a diagnostic marker of severe proximal tubular injury. NEW & NOTEWORTHY: This study provides novel insights into the distribution of kidney ACE2 in a model of AKI by IRI showing a striking detachment of apical ACE2 from proximal tubules and its loss in urine and urine sediment. The observed deficiency of kidney ACE2 protein and enzymatic activity in severe AKI suggests that administration of forms of this enzyme may mitigate AKI and that urinary ACE2 may serve as a potential biomarker for tubular injury. [ABSTRACT FROM AUTHOR]

Angiotensin-converting enzymes (ACE) are well-known for their roles in both blood pressure regulation via the renin-angiotensin system as well as functions in fertility, immunity, hematopoiesis, and many others. The two main isoforms of ACE include ACE and ACE-2 (ACE2). Both isoforms have similar structures and mediate numerous effects on the cardiovascular system. Most remarkably, ACE2 serves as an entry receptor for SARS-CoV-2. Understanding the interaction between the virus and ACE2 is vital to combating the disease and preventing a similar pandemic in the future. Noninvasive imaging techniques such as positron emission tomography and single photon emission computed tomography could noninvasively and quantitatively assess in vivo ACE2 expression levels. ACE2-targeted imaging can be used as a valuable tool to better understand the mechanism of the infection process and the potential roles of ACE2 in homeostasis and related diseases. Together, this information can aid in the identification of potential therapeutic drugs for infectious diseases, cancer, and many ACE2-related diseases. The present review summarized the state-of-the-art radiotracers for ACE2 imaging, including their chemical design, pharmacological properties, radiochemistry, as well as preclinical and human molecular imaging findings. We also discussed the advantages and limitations of the currently developed ACE2-specific radiotracers. [ABSTRACT FROM AUTHOR]

Aortic aneurysm (AA) is an aortic disease with a high mortality rate, and other than surgery no effective preventive or therapeutic treatment have been developed. The renin–angiotensin system (RAS) is an important endocrine system that regulates vascular health. The ACE2/Ang‐(1–7)/MasR axis can antagonize the adverse effects of the activation of the ACE/Ang II/AT1R axis on vascular dysfunction, atherosclerosis, and the development of aneurysms, thus providing an important therapeutic target for the prevention and treatment of AA. However, products targeting the Ang‐(1–7)/MasR pathway still lack clinical validation. This review will outline the epidemiology of AA, including thoracic, abdominal, and thoracoabdominal AA, as well as current diagnostic and treatment strategies. Due to the highest incidence and most extensive research on abdominal AA (AAA), we will focus on AAA to explain the role of the RAS in its development, the protective function of Ang‐(1–7)/MasR, and the mechanisms involved. We will also describe the roles of agonists and antagonists, suggest improvements in engineering and drug delivery, and provide evidence for Ang‐(1–7)/MasR's clinical potential, discussing risks and solutions for clinical use. This study will enhance our understanding of AA and offer new possibilities and promising targets for therapeutic intervention. [ABSTRACT FROM AUTHOR]

Background: Nearly half of patients with heart failure (HF) have preserved ejection fraction (EF) and the mortality and morbidity of patients with HF with preserved EF (HFpEF) are high. Patients with HFpEF are often elderly and their primary chronic symptom is severe exercise intolerance. Due to the frequent coexistence of hypertension in HFpEF patients, the use of anti-hypertensive medications is common in their treatment. While many cohort studies and several randomized controlled trials (RCTs) have examined the effectiveness of various anti-hypertensive drugs such as beta-blockers and renin-angiotensin system inhibitors in HFpEF, the role of calcium channel blockers (CCBs) remains uncertain. Despite several RCTs and cohort studies exploring the effects of CCBs on prognosis and exercise capacity in HFpEF patients, the findings have been inconsistent, likely due to limited statistical power and/or variations in study design. Therefore, our aim is to conduct a systematic review and meta-analysis of studies on the effects of CCBs in these patients. Methods: This meta-analysis will include RCTs and cohort studies on the effect of CCBs in HFpEF patients. Information of studies will be collected from PubMed, Web of Science, and Scopus. The primary outcome of interest will be prognosis. The secondary outcome of interest will be exercise capacity. Discussion: Synthesizing our meta-analytical results with expert consensus could contribute to the formulation of updated clinical guidelines. Our systematic review and meta-analysis will provide directions for future research on the use of CCBs in HFpEF patients. Systematic review registration: INPLASY202430097. [ABSTRACT FROM AUTHOR]

Introduction: There remains an unmet need to reduce kidney and cardiovascular risk in patients with chronic kidney disease (CKD). This report is therefore intended to provide real-world clinical guidance to primary care providers on sodium-glucose co-transporter-2 (SGLT2) inhibitor use in patients with CKD, focusing on practical considerations. Initially developed as glucose-lowering drugs, SGLT2 inhibitors preserve kidney function and reduce risks of cardiovascular events and mortality. Clinical benefits of SGLT2 inhibitors in CKD have been demonstrated in multiple clinical trials, yet utilization in practice remains relatively low, likely due to the complexity of labeled indications (past and present) and misconceptions about SGLT2 inhibitors as a class. Methods: A panel of 8 US-based nephrologists convened in August 2022 to develop consensus guidance for the primary care community surrounding risk assessment as well as initiation and implementation of SGLT2 inhibitors in patients with CKD. Here, we provide an adapted version of the Kidney Disease: Improving Global Outcomes (KDIGO) heatmap and a treatment-decision algorithm. Conclusions: We advocate SGLT2 inhibitors as co-first-line therapy with renin-angiotensin-aldosterone system (RAAS) inhibitors, where RAAS inhibitor dose titration need not be completed before initiation of an SGLT2 inhibitor. In fact, SGLT2 inhibitor therapy may facilitate up-titration or maintenance of optimal RAAS inhibitor dosing. We describe potential strategies to aid implementation of an SGLT2 inhibitor in clinical practice, including improving education and awareness among care providers and patients and dispelling misconceptions about the safety of SGLT2 inhibitors. In summary, we support the use of SGLT2 inhibitors with RAAS inhibitors as co-first-line therapy in most patients with CKD. [ABSTRACT FROM AUTHOR]

Lactoferrin, a glycoprotein derived from breastmilk, is recognized for its health benefits in infants and children; however, its protective effects when administered during gestation and lactation against offspring hypertension remain unclear. This study aimed to investigate whether maternal lactoferrin supplementation could prevent hypertension in offspring born to mothers with chronic kidney disease (CKD), with a focus on nitric oxide (NO), renin–angiotensin system (RAS) regulation, and alterations in gut microbiota and short-chain fatty acids (SCFAs). Prior to pregnancy, female rats were subjected to a 0.5% adenine diet for 3 weeks to induce CKD. During pregnancy and lactation, pregnant rats received one of four diets: normal chow, 0.5% adenine diet, 10% lactoferrin diet, or adenine diet supplemented with lactoferrin. Male offspring were euthanized at 12 weeks of age (n = 8 per group). Supplementation with lactoferrin during gestation and lactation prevented hypertension in adult offspring induced by a maternal adenine diet. The maternal adenine diet caused a decrease in the index of NO availability, which was restored by 67% with maternal LF supplementation. Additionally, LF was related to the regulation of the RAS, as evidenced by a reduced renal expression of renin and the angiotensin II type 1 receptor. Combined maternal adenine and LF diets altered beta diversity, shifted the offspring's gut microbiota, decreased propionate levels, and reduced the renal expression of SCFA receptors. The beneficial effects of lactoferrin are likely mediated through enhanced NO availability, rebalancing the RAS, and alterations in gut microbiota composition and SCFAs. Our findings suggest that maternal lactoferrin supplementation improves hypertension in offspring in a model of adenine-induced CKD, bringing us closer to potentially translating lactoferrin supplementation clinically for children born to mothers with CKD. [ABSTRACT FROM AUTHOR]

Background: Prior research has highlighted the association between uric acid (UA) and the activation of the renin-angiotensin-aldosterone system (RAAS). However, the specific relationship between aldosterone, the RAAS's end product, and UA-related diseases remains poorly understood. This study aims to clarify the impact of aldosterone on the development and progression of hyperuricemia and gout in hypertensive patients. Methods: Our study involved 34534 hypertensive participants, assessing plasma aldosterone concentration (PAC)'s role in UA-related diseases, mainly hyperuricemia and gout. We applied multiple logistic regression to investigate the impact of PAC and used restricted cubic splines (RCS) for examining the dose-response relationship between PAC and these diseases. To gain deeper insights, we conducted threshold analyses, further clarifying the nature of this relationship. Finally, we undertook subgroup analyses to evaluate PAC's effects across diverse conditions and among different subgroups. Results: Multivariate logistic regression analysis revealed a significant correlation between the occurrence of hyperuricemia and gout and the elevation of PAC levels. Compared to the first quartile (Q1) group, groups Q2, Q3, and Q4 all exhibited a significantly increased risk of occurrence. Moreover, the conducted RCS analysis demonstrated a significant nonlinear dose-response relationship, especially when PAC was greater than 14 ng/dL, with a further increased risk of hyperuricemia and gout. Finally, comprehensive subgroup analyses consistently reinforced these findings. Conclusion: This study demonstrates a close association between elevated PAC levels and the development of UA-related diseases, namely hyperuricemia and gout, in hypertensive patients. Further prospective studies are warranted to confirm and validate this relationship. [ABSTRACT FROM AUTHOR]

The harsh and dry conditions of desert environments have resulted in genomic adaptations, allowing for desert organisms to withstand prolonged drought, extreme temperatures, and limited food resources. Here, we present a comprehensive exploration of gene expression across five tissues (kidney, liver, lung, gastrointestinal tract, and hypothalamus) and 19 phenotypic measurements to explore the whole-organism physiological and genomic response to water deprivation in the desert-adapted cactus mouse (Peromyscus eremicus). The findings encompass the identification of differentially expressed genes and correlative analysis between phenotypes and gene expression patterns across multiple tissues. Specifically, we found robust activation of the vasopressin renin-angiotensin-aldosterone system (RAAS) pathways, whose primary function is to manage water and solute balance. Animals reduced food intake during water deprivation, and upregulation of PCK1 highlights the adaptive response to reduced oral intake via its actions aimed at maintained serum glucose levels. Even with such responses to maintain water balance, hemoconcentration still occurred, prompting a protective downregulation of genes responsible for the production of clotting factors while simultaneously enhancing angiogenesis which is thought to maintain tissue perfusion. In this study, we elucidate the complex mechanisms involved in water balance in the desert-adapted cactus mouse, P. eremicus. By prioritizing a comprehensive analysis of whole-organism physiology and multi-tissue gene expression in a simulated desert environment, we describe the complex response of regulatory processes. [ABSTRACT FROM AUTHOR]

Introduction The DAPA-CKD study showed a protective effect of dapagliflozin on kidney function in chronic kidney disease (CKD) patients with and without diabetes mellitus. Although dapagliflozin is expected to be effective also in CKD patients with autosomal dominant polycystic kidney disease (ADPKD), its efficacy and safety in this population remain unknown because ADPKD was an exclusion criterion in the DAPA-CKD study. Therefore, we evaluated the effects of dapagliflozin in CKD patients with ADPKD. Methods We performed a retrospective observational study of seven patients with ADPKD treated with dapagliflozin at Toranomon Hospital, Tokyo, Japan. We analyzed changes in estimated glomerular filtration rate (eGFR) slope and annual height-corrected total kidney volume before and after starting dapagliflozin treatment. Results The median observation period after starting dapagliflozin was 20 months. Four patients received concomitant tolvaptan. The eGFR slope before and after initiation of dapagliflozin could be calculated in six patients and improved in all of them except the one who did not receive a renin-angiotensin system (RAS) inhibitor. Annual height-corrected total kidney volume increased in all patients. Concurrent tolvaptan treatment had no effect. Conclusion In CKD patients with ADPKD, dapagliflozin may increase kidney volume but may have a protective effect on kidney function when used concomitantly with RAS inhibitors. [ABSTRACT FROM AUTHOR]

Atherosclerosis (As) is a chronic inflammatory disease caused by lipid deposition. Panvascular diseases, which are mainly caused by As, have gradually attracted the attention of many scholars, and their main pathological features are vascular lesions. Vitamin D plays an important role in anti-As in panvascular diseases. It is involved in the regulation of renin-angiotensin system ( RAS), endothelial cell injury, immune response, neutrophil extracellular traps (NET) regulation, apoptosis and autophagy, and is a new target in panvascular diseases research. Traditional Chinese Medicine (TCM) has certain advantages in the prevention and treatment of panvascular diseases. Among them, single herbs, active ingredients and compound prescriptions can regulate vitamin D-related metabolism, and have unique scientific value for the prevention and treatment of As. This article mainly discusses the role of vitamin D in multiple pathological links of panvascular diseases and related Chinese medicine interventions, aiming to provide effective ideas for the prevention and treatment of panvascular diseases from the perspective of vitamin D. [ABSTRACT FROM AUTHOR]

The angiotensin-converting enzyme inhibitors (ACEi) are widely prescribed anti-hypertensive drugs that target the renin-angiotensin system (RAS). Yet, these drugs have limitations due to their side effects. This study aims to explore the potential of bioactive compounds from andaliman fruit (Zanthoxylum acanthopodium DC.) as safer natural ACE inhibitors for hypertension treatment using an in-silico approach. Phytoconstituents from Z. acanthopodium fruits were screened using the SwissADME web server to assess their bioavailability, while their bioactivity was predicted by PASS online web server. Selected compounds were then docked to human ACE (PDB ID: 1O86) by site-specific docking to the ACE binding pocket. The stability of protein-ligand interactions was evaluated using molecular dynamics simulations in YASARA software. The possible toxicity of the selected compounds then evaluated using protox web server. Out of 39 compounds tested, we predicted that five compounds, namely kaempferol, quercetin, abscisic acid, benzophenone, and cis-3,5,3',4'-tetrahydroxystilbene could bind to ACE with good affinity and formed interactions with key residues. The presence of these compounds might reduce the binding affinity of angiotensin I toward ACE and altered the interaction site. Molecular dynamics simulations demonstrate that these compounds exhibit good interaction stability with ACE and remained in the active site throughout the simulation. This study showed that five bioactive compounds from andaliman fruit act potentially as natural ACE inhibitor agents. [ABSTRACT FROM AUTHOR]

Background: Aortic dissection (AD) is a lethal cardiovascular emergency involving high mortality and disability. However, its specific pathogenesis remains to be elucidated. Methods: A bibliometric analysis based on the Web of Science database, VOSviewer software and Citex platforms was conducted to have a knowledge of the development trends, frontiers and hot spots of AD. Subsequently, the top five AD‐related genes from the titles and abstracts of published literature were searched. Lastly, the roles of the top five genes and their encoded proteins in the onset of AD were reviewed. Results: The bibliometrics showed that most studies are exploring the molecular drivers related to AD, especially gene mutations. The top five AD‐related genes were transforming growth factor‐β (TGFB)‐related genes, elastin (ELN), fibrillin‐1 (FBN1), angiotensinogen (AGT) and matrix metalloproteinase 9 (MMP9). In particular, regulation of the structure of elastic fiber by TGFB‐related genes, ELN and FBN1, appears to be the principal mechanism contributing to AD onset. Activation of the renin‐angiotensin system is the principal mechanism by which AGT triggers AD. MMP9 promotes the formation and development of AD by degrading extracellular matrix components. Conclusion: TGFB, ELN, FBN1, AGT and MMP9 are the five top molecular drivers of AD, providing a comprehensive mechanistic insight into AD. [ABSTRACT FROM AUTHOR]

Insulin signaling is vital for regulating cellular metabolism, growth, and survival pathways, particularly in tissues such as adipose, skeletal muscle, liver, and brain. Its role in the heart, however, is less well-explored. The heart, requiring significant ATP to fuel its contractile machinery, relies on insulin signaling to manage myocardial substrate supply and directly affect cardiac muscle metabolism. This review investigates the insulin–heart axis, focusing on insulin's multifaceted influence on cardiac function, from metabolic regulation to the development of physiological cardiac hypertrophy. A central theme of this review is the pathophysiology of insulin resistance and its profound implications for cardiac health. We discuss the intricate molecular mechanisms by which insulin signaling modulates glucose and fatty acid metabolism in cardiomyocytes, emphasizing its pivotal role in maintaining cardiac energy homeostasis. Insulin resistance disrupts these processes, leading to significant cardiac metabolic disturbances, autonomic dysfunction, subcellular signaling abnormalities, and activation of the renin–angiotensin–aldosterone system. These factors collectively contribute to the progression of diabetic cardiomyopathy and other cardiovascular diseases. Insulin resistance is linked to hypertrophy, fibrosis, diastolic dysfunction, and systolic heart failure, exacerbating the risk of coronary artery disease and heart failure. Understanding the insulin–heart axis is crucial for developing therapeutic strategies to mitigate the cardiovascular complications associated with insulin resistance and diabetes. [ABSTRACT FROM AUTHOR]

Endothelium plays a fundamental role in the cardiovascular system, forming an interface between blood and adjacent tissues by regulating the vascular tone through the synthesis of nitric oxide, prostaglandins and other relaxing factors. Endothelial dysfunction is characterized by vasoconstriction, cell proliferation and shifting toward a proinflammatory and prothrombic state. In hypertension endothelial dysfunction may be involved in the initiation and development of vascular inflammation, vascular remodeling, and atherosclerosis and is independently associated with increased cardiovascular risk. Different conditions such as impaired vascular shear stress, inflammation and oxidative stress, activation of the renin angiotensin system have been described as important pathophysiological mechanisms involved in the development of endothelial dysfunction. The release of extracellular vesicles by neighboring cells in the vascular wall has emerged as an important regulator of endothelial function and with potential antihypertensive properties and beneficial effects by counteracting the hypertension mediated organ damage. Furthermore, macrovesicles are emerging as an innovative therapeutic approach for vascular protection, allowing the delivery of bioactive molecules, such as miRNA and drugs interacting with the renin angiotensin system. [ABSTRACT FROM AUTHOR]

Objective: Dihydropyridine calcium channel blocker (DHP-CCBs) is an appropriate add-on antihypertensive option for uncontrolled blood pressure diabetic hypertensive patients with albuminuria who are already taking renin-angiotensin system blockers (RASBs). Among DHP-CCBs, amlodipine is the first-line medication in combination with RASBs. However, new-generation DHP-CCBs like lercanidipine has demonstrated superior effectiveness and fewer side effects, although at a higher cost than amlodipine. This study aims to assess the cost-effectiveness of lercanidipine versus amlodipine when added to RASBs in diabetic hypertensive patients with albuminuria. The objective is to provide robust evidence guiding the selection of the most suitable and worthwhile treatment option in Thailand. Materials and Methods: This study analyses the cost-effectiveness of lercanidipine versus amlodipine as an addition to RASBs in diabetic hypertensive patients with albuminuria. The analysis was conducted from a societal perspective using a Markov model. Results: The total costs of lercanidipine and amlodipine treatments were 370,392.83 baht and 384,221.85 baht, respectively. The life years gained for lercanidipine and amlodipine treatments were 11.33 years and 10.96 years respectively. Additionally, the quality-adjusted life years (QALYs) of lercanidipine and amlodipine treatments were 8.06 years and 7.51 years respectively. The calculated ICER was negative, indicating treatment with lercanidipine as a dominant strategy. Conclusion: Due to lercanidipine’s noticeable cost-effectiveness, lower costs, and longer QALYs. Adding lercanidipine has proven to be more cost-effective than amlodipine for diabetic hypertensive patients with albuminuria who have been unable to achieve their blood pressure goals with RASBs alone. Therefore, lercanidipine should be the preferred choice as an add-on to RASBs in Thailand. These results could significantly aid policymakers in making informed decisions. [ABSTRACT FROM AUTHOR]

Male infertility represents a significant public health concern. There is a negative impact of inflammatory bowel diseases (IBDs) on the male reproductive system. The aim of this study was to investigate whether oat beta-glucan (OBG) with different molar mass can modulate parameters of antioxidant defense and inflammatory response in the testes of adult Sprague–Dawley rats with TNBS-induced colitis and whether the OBG intervention can modulate the inflammatory response in association with the RAS system. Results: higher testicular superoxide dismutase (SOD), glutathione reductase (GR) activities and glutathione (GSH) concentration, and lower testosterone (T) level and glutathione peroxidase (GPx) activity, were observed in rats with colitis than in healthy control ones. TNBS-induced colitis resulted in decreased the angiotensin 1–7 (ANG 1–7) level in the testes of rats fed with low-molar mass OBG compared to control animals. Conclusions: although colitis induced moderate pro-oxidant changes in the gonads, it seems plausible that dietary intervention with different fractions of oat beta-glucans mass may support the maintenance of reproductive homeostasis via the stimulation of the local antioxidant defense system. [ABSTRACT FROM AUTHOR]

During the perioperative period of transplantation, patients experience hypotension secondary to the side effects of anesthesia, surgical stress, inflammatory triggering, and intraoperative fluid shifts, among others causes. Vasopressor support, in this context, must reverse systemic hypotension, but ideally, the agents used should benefit allograft function and avoid the adverse events commonly seen after transplantation. Traditional therapies to reverse hypotension include catecholamine vasopressors (norepinephrine, epinephrine, dopamine, and phenylephrine), but their utility is limited when considering allograft complications and adverse events such as arrhythmias with agents with beta-adrenergic properties. Synthetic angiotensin II (AT2S–[Giapreza]) is a novel vasopressor indicated for distributive shock with a unique mechanism of action as an angiotensin receptor agonist restoring balance to an often-disrupted renin angiotensin aldosterone system. Additionally, AT2S provides a balanced afferent and efferent arteriole vasoconstriction at the level of the kidney and could avoid the arrhythmic complications of a beta-adrenergic agonist. While the data, to date, are limited, AT2S has demonstrated safety in case reports, pilot studies, and small series in the kidney, liver, heart, and lung transplant populations. There are physiologic and hemodynamic reasons why AT2S could be a more utilized agent in these populations, but further investigation is warranted. [ABSTRACT FROM AUTHOR]

α-Lipoic acid (LA) is an antioxidant of endogenous production, also obtained exogenously. Oxidative stress is closely associated with hypertension, which causes kidney injury and endothelial dysfunction. Here, we evaluated the cardiovascular and renal effects of LA in the two-kidney-one-clip (2K1C) hypertension model. The rats were divided into four groups: Sham surgery (Sham), the two-kidneys-one-clip (2K1C) group, and groups treated with LA for 14 days (Sham-LA and 2K1C-LA). No changes were observed in the pattern of food, water intake, and urinary volume. The left/right kidney weight LKw/RKw ratio was significantly higher in 2K1C animals. LA treatment did not reverse the increase in cardiac mass. In relation to vascular reactivity, there was an increase in the potency of phenylephrine (PHE) curve in the hypertensive animals treated with LA compared to the 2K1C group and also compared to the Sham group. Vasorelaxation induced by acetylcholine (Ach) and sodium nitroprusside (SNP) were not improved by treatment with LA. Urea and creatinine levels were not altered by the LA treatment. In conclusion, the morphological changes in the aorta and heart were not reversed; however, the treatment with LA mitigated the contraction increase induced by the 2K1C hypertension. [ABSTRACT FROM AUTHOR]

Background: Aberrant activation of the classic renin-angiotensin system (RAS) and intestinal micro dysbiosis adversely affect insulin resistance (IR), dyslipidemia, and other metabolic syndrome markers. However, the action of angiotensinconverting enzyme 2 (ACE2) and gut health in systemic homeostasis vary, and their interaction is not completely understood. Methods: We adopted a combinatory approach of metabolomics and fecal 16S rRNA analysis to investigate gut microbiota and metabolite in two different mouse models, ACE2 knockout (ACE2 KO) mice and the ACE2-overexpressing obese mice. Results: 16S rRNA gene sequencing revealed that ACE2 influences microbial community composition and function, and ACE2 KO mice had increased Deferribacteres, Alcaligenaceae, Parasutterella, Catenibacterium, and Anaerotruncus, with decreased short-chain fatty acid (SCFA)-producing bacteria (Marvinbryantia and Alistipes). In contrast, ACE2-overexpressed mice exhibited increased anti-inflammatory probiotic (Oscillospiraceae, Marinifilaceae, and Bifidobacteriaceae) and SCFA-producing microbes (Rikenellaceae, Muribaculaceae, Ruminococcaceae, Odoribacter, and Alistipes) and decreased Firmicutes/Bacteroidetes, Lactobacillaceae, Erysipelotrichaceae, and Lachnospiraceae. Metabolome analysis indicated differential metabolites in ACE2 KO and ACE2-overexpression mice, especially the glucolipid metabolismrelated compounds. Furthermore, correlation analysis between gut microbiota and metabolites showed a dynamic mutual influence affecting host health. Conclusion: Our study confirms for the first time a significant association between ACE2 status and gut microbiome and metabolome profiles, providing a novel mechanism for the positive effect of ACE2 on energy homeostasis. [ABSTRACT FROM AUTHOR]

Background: The COVID‐19 virus not only has significant pathogenicity but also influences the progression of many diseases, altering patient prognosis. Cardiovascular diseases, particularly aortic aneurysms, are among the most life‐threatening conditions. Main Idea: COVID‐19 infection is reported to accelerate the progression of abdominal aortic aneurysms (AAAs) and increase the risk of rupture; however, a comprehensive understanding of the underlying mechanisms remains elusive. This article primarily reviews the relevant foundational research, focusing on disruptions in the renin‐angiotensin‐aldosterone system (RAAS), immune system activation, and coagulation disorders. Furthermore, we summarize related clinical research, including the epidemiology of aortic aneurysms during the pandemic and specific case studies. Conclusion: COVID‐19 infection can influence the onset and progression of aortic aneurysms by affecting the RAAS, triggering inflammation and immune dysregulation in the arterial wall, and inducing a hypercoagulation state. It is crucial to comprehensively understand the impact of pandemic viral infections on aortic diseases at the foundational and clinical levels, thereby identifying potential preventative or therapeutic approaches and preparing for potential future outbreaks. [ABSTRACT FROM AUTHOR]

Renin-angiotensin system (RAS) modulators, including Angiotensin receptor blockers (ARB) and angiotensin-converting enzyme inhibitors (ACEI), are effective medications for controlling blood pressure. Cognitive deficits, including lack of concentration, memory loss, and confusion, were reported after COVID-19 infection. ARBs or ACEI increase the expression of angiotensin-converting enzyme-2 (ACE-2), a functional receptor that allows binding of SARS-CoV-2 spike protein for cellular invasion. To date, the association between the use of RAS modulators and the severity of COVID-19 cognitive dysfunction is still controversial. Purpose: This study addressed the following questions: 1) Does prior treatment with RAS modulator worsen COVID-19-induced cerebrovascular and cognitive dysfunction? 2) Can post-treatment with RAS modulator improve cognitive performance and cerebrovascular function following COVID-19? We hypothesize that pre-treatment exacerbates COVID-19-induced detrimental effects while post-treatment displays protective effects. Methods: Clinical study: Patients diagnosed with COVID-19 between May 2020 and December 2022 were identified through the electronic medical record system. Inclusion criteria comprised a documented medical history of hypertension treated with at least one antihypertensive medication. Subsequently, patients were categorized into two groups: those who had been prescribed ACEIs or ARBs before admission and those who had not received such treatment before admission. Each patient was evaluated on admission for signs of neurologic dysfunction. Pre-clinical study: Humanized ACE-2 transgenic knock-in mice received the SARS-CoV-2 spike protein via jugular vein injection for 2 weeks. One group had received Losartan (10 mg/kg), an ARB, in their drinking water for two weeks before the injection, while the other group began Losartan treatment after the spike protein injection. Cognitive functions, cerebral blood flow, and cerebrovascular density were determined in all experimental groups. Moreover, vascular inflammation and cell death were assessed. Results: Signs of neurological dysfunction were observed in 97 out of 177 patients (51%) taking ACEIs/ARBs prior to admission, compared to 32 out of 118 patients (27%) not receiving ACEI or ARBs. In animal studies, spike protein injection increased vascular inflammation, increased endothelial cell apoptosis, and reduced cerebrovascular density. In parallel, spike protein decreased cerebral blood flow and cognitive function. Our results showed that pretreatment with Losartan exacerbated these effects. However, post-treatment with Losartan prevented spike protein-induced vascular and neurological dysfunctions. Conclusion: Our clinical data showed that the use of RAS modulators before encountering COVID-19 can initially exacerbate vascular and neurological dysfunctions. Similar findings were demonstrated in the in-vivo experiments; however, the protective effects of targeting the RAS become apparent in the animal model when the treatment is initiated after spike protein injection. [ABSTRACT FROM AUTHOR]

Background: The management in primary care (PC) of the patients with Heart Failure (HF) is different from the management hospital, in a special way compared to cardiology departments. Objective: To define the characteristics in both phenotypes of HF in prevalent and incident cases of HF in patients recruited in a large PC sample. Methods: We proposed a and longitudinal analyses, in patients of the IBERICAN cohort, that recruited 8,066 patients in the Spanish primary care system, with 15,488 patients-years of follow-up. Of them, 252 patients (3.1%) had diagnoses of HF. HF was classified according to the 2014 guidelines in two groups: HF with a reduced eject fraction or HFrEF (LVEF < 50%) and HF with preserved eject fraction or HFpEF (LVEF ≥ 50%). Recommended treatment was defined as the patient receiving drug treatment with Renin-Angiotensin-System (RAS) blockers with beta-blockers and, optionally, spironolactone. The incidence of new cases of HF was calculated in the 7,814 patients without HF in the inclusion visit. Finally, we analysed which variables associated the onset new cases and get the hazard ratio (HR) with the confidence interval at 95% ([95%CI]). Clinical trials register: NCT02261441 (02/05/2017). Results: The HFpEF was the most frequent phenotype in prevalent cases (61.1%) and incident cases (73.9%). Patients with HFrEF had a higher prevalence of coronary heart disease (p = 0.008) and PAD (p = 0.028), and no statistically significant differences was observed in the therapeutic groups used between both groups. The incidence of HF was 12.8 cases/1000 inhabitants/year, 35.6% of them was diagnosed in PC. The renin-angiotensin system blockers were more used in PC (60%) and beta-blockers (100%) and spironolactone (60%) in hospital. The female sex showed a protective effect for incident cases (0.51 [0.28–0.92]); and AF (HR [95%CI]: 2.90 [1.51–5.54]), coronary heart disease (HR [95%CI]: 2.18 [1.19-4.00]) and hypertension (HR [95%CI]: 1.91 [1.00-3.64]) increased the risk of developing HF. Conclusions: HF phenotype more frequent and incident in PC was the HFpEF, but only one third of them are diagnosed in PC level. The female sex showed a protective effect and atrial fibrillation, ischaemic heart disease and hypertension increased the risk of develop HF. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) is associated with the progressive loss of functional nephrons and hypertension (HTN). Clinical studies demonstrate calcium channel blocker (CCB) therapy mitigates the decline in renal function in humans with essential HTN. However, there are few long-term clinical studies that determine the impact of CCBs in patients with hypertensive CKD. African Americans (AA) have a higher prevalence of CKD and a faster progression to total kidney failure as compared to the white population but the mechanisms are poorly understood. Both clinical evidence (the African American Study of Kidney Disease and Hypertension, or AASK trial) and experimental studies have demonstrated that CCB may expose glomerular capillaries to high systemic pressures and exacerbate CKD progression. Therefore, using a large physiological model, we set out to replicate the AASK trial findings, predict renal hemodynamic responses and the role of the renin-angiotensin system during CCB antihypertensive therapy in a virtual population, and hypothesize mechanisms underlying those findings. Our current mathematical model, HumMod, is comprised of integrated systems that play an integral role in long-term blood pressure (BP) control such as neural, endocrine, circulatory, and renal systems. Parameters (n = 341) that control these systems were randomly varied and resulted in 1,400 unique models that we define as a virtual population. We calibrated these models to individual patient level data from the AASK trial: BP and glomerular filtration rate (GFR) before and after 3 years of amlodipine (10 mg/day). After calibration, the new virtual population (n = 165) was associated with statistically similar BP and GFR before and after CCB. Baseline factors such as elevated single nephron GFR and low tubuloglomerular feedback were correlated with greater declines in renal function and increased glomerulosclerosis after 3 years of CCB. Blocking the renin-angiotensin system (RAS) in the virtual population decreased glomerular pressure, limited glomerular damage, and further decreased BP (-14 ± 8 mmHg) as compared to CCB alone (-11 ± 9 mmHg). Our simulations echo the potential risk of CCB monotherapy in AA CKD patients and support blockade of the renin angiotensin system as a valuable tool in renal disease treatment when combined with CCB therapy. [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD) is the leading cause of morbimortality in Europe and worldwide. CVD imposes a heterogeneous spectrum of cardiac remodelling, depending on the insult nature, that is, pressure or volume overload, ischaemia, arrhythmias, infection, pathogenic gene variant, or cardiotoxicity. Moreover, the progression of CVD‐induced remodelling is influenced by sex, age, genetic background and comorbidities, impacting patients' outcomes and prognosis. Cardiac reverse remodelling (RR) is defined as any normative improvement in cardiac geometry and function, driven by therapeutic interventions and rarely occurring spontaneously. While RR is the outcome desired for most CVD treatments, they often only slow/halt its progression or modify risk factors, calling for novel and more timely RR approaches. Interventions triggering RR depend on the myocardial insult and include drugs (renin–angiotensin–aldosterone system inhibitors, beta‐blockers, diuretics and sodium–glucose cotransporter 2 inhibitors), devices (cardiac resynchronization therapy, ventricular assist devices), surgeries (valve replacement, coronary artery bypass graft), or physiological responses (deconditioning, postpartum). Subsequently, cardiac RR is inferred from the degree of normalization of left ventricular mass, ejection fraction and end‐diastolic/end‐systolic volumes, whose extent often correlates with patients' prognosis. However, strategies aimed at achieving sustained cardiac improvement, predictive models assessing the extent of RR, or even clinical endpoints that allow for distinguishing complete from incomplete RR or adverse remodelling objectively, remain limited and controversial. This scientific statement aims to define RR, clarify its underlying (patho)physiologic mechanisms and address (non)pharmacological options and promising strategies to promote RR, focusing on the left heart. We highlight the predictors of the extent of RR and review the prognostic significance/impact of incomplete RR/adverse remodelling. Lastly, we present an overview of RR animal models and potential future strategies under pre‐clinical evaluation. [ABSTRACT FROM AUTHOR]

The aim of this study is to review the role of renin-angiotensin in skin regeneration and wound healing with a focus on molecular mechanisms. Angiotensin receptor type 1 (AT1R) are abundant in the wounded area, and thus, lead to the activation of ERK, STAT1, and STAT3 which can lead to epidermal self-renewal. The expression of Renin Angiotensin System (RAS) components was significantly lower in wounds caused by burning, rather than intact skin, noting that RAS is involved in the re-epithelialization of skin. ERK, STAT and STAT3 are the targets of Ang II, indicating that RAS active components are involved in fibroblast, stem cells and keratinocyte migration. The effect of inhibiting the RAS on wound healing is context-dependent. On one hand, it is suggested that inhibiting RAS during this phase may slow down wound healing speed. On the other hand, studies have shown that RAS inhibition in this phase can lead to α-SMA activation, ultimately accelerating the wound healing process. Most of the investigations indicate that the inhibition of RAS with Angiotensin Receptor Blockers (ARBs) and Angiotensin Converting Enzyme (ACE) plays a significant role in tissue remodeling in the last phase of wound healing. It has been shown that the inhibition of RAS can inhibit scar formation and fibrosis through the downregulation of inflammatory and fibrogenic agents, such as TGF-β, SMAD2/3, and TAK1, PDGF-BB, and HSP47. To sum up, that local administration of RAS regulators might lead to less scar formation and inflammation in the last phase of wound closure. [ABSTRACT FROM AUTHOR]

The renin‐angiotensin system (RAS) regulates systemic and cerebral blood flow and is dysregulated in dementia. The major aim of this study was to determine if RAS signalling is dysregulated in vascular dementia. We measured markers of RAS signalling in white matter underlying the frontal and occipital cortex in neuropathologically confirmed cases of vascular dementia (n = 42), Alzheimer's disease (n = 50), mixed AD/VaD (n = 50) and age‐matched controls (n = 50). All cases were stratified according to small vessel disease (SVD) severity across both regions. ACE‐1 and ACE‐2 protein and activity was measured by ELISA and fluorogenic peptide assays respectively, and angiotensin peptide (Ang‐II, Ang‐III and Ang‐(1–7)) levels were measured by ELISA. ACE‐1 protein level and enzyme activity, and Ang‐II and Ang‐III, were elevated in the white matter in vascular dementia in relation to SVD severity. ACE‐1 and Ang‐II protein levels were inversely related to MAG:PLP1 ratio, a biochemical marker of brain tissue oxygenation that when reduced indicates cerebral hypoperfusion, in a subset of cases. ACE‐2 level was elevated in frontal white matter in vascular dementia. Ang‐(1–7) level was elevated across all dementia groups compared to age‐matched controls but was not related to SVD severity. RAS signalling was not altered in the white matter in Alzheimer's disease. In the overlying frontal cortex, ACE‐1 protein was reduced and ACE‐2 protein increased in vascular dementia, whereas angiotensin peptide levels were unchanged. These data indicate that RAS signalling is dysregulated in the white matter in vascular dementia and may contribute to the pathogenesis of small vessel disease. [ABSTRACT FROM AUTHOR]

At present, there are few reports about the proteomics changes provoked by butylated hydroxytoluene (BHT) supplementation on cryopreserved semen in mammals. Thus, we aimed to evaluate the effects of different concentrations of BHT on goat sperm and to investigate the proteomics changes of adding BHT to cryopreserved goat (Capra hircus) sperm. Firstly, semen samples were collected from four goats, and frozen in the basic extenders containing different concentrations of BHT (0.5 mM, 1.0 mM, 2.0 mM) and a control without BHT, respectively. After thawing, the protective effects of dose-dependent replenished BHT to the freezing medium on post-thaw sperm motility, integrities of plasma membrane and acrosome, reactive oxygen species levels were confirmed, with 0.5 mM BHT being the best (B group) as compared to the control (without BHT, C group). Afterwards, TMT-based quantitative proteomic technique was performed to profile proteome of the goat sperm between C group and B group. Parallel reaction monitoring was used to confirm reliability of the data. Overall, 2,476 proteins were identified and quantified via this approach. Comparing the C and B groups directly (C vs. B), there were 17 differentially abundant proteins (DAPs) po-tentially associated with sperm characteristics and functions were identified, wherein three were upregulated and 14 were downregulated, respectively. GO annotation analysis demonstrated the potential involvement of the identified DAPs in metabolic process, multi-organism process, reproduction, reproductive process, and cellular process. KEGG enrichment analysis further indicated their potential roles in renin-angiotensin system and glutathione metabolism pathways. Together, this novel study clearly shows that BHT can effectively improve quality parameters and fertility potential of post-thawed goat sperm at the optimal concentration, and its cryoprotection may be realized through regulation of sperm metabolism and antioxidative capability from the perspective of sperm proteomic modification. [ABSTRACT FROM AUTHOR]

BACKGROUND: The physiological effects of renin-angiotensin system modulation in acute respiratory distress syndrome (ARDS) remain controversial and have not been investigated in randomized trials. We sought to determine whether angiotensin-II treatment is associated with improved oxygenation in shock-associated ARDS. METHODS: Post-hoc subgroup analysis of the Angiotensin Therapy for High Output Shock (ATHOS-3) trial. We studied patients who met modified Berlin ARDS criteria at enrollment. The primary outcome was PaO2/FiO2-ratio (P:F) at 48-h adjusted for baseline P:F. Secondary outcomes included oxygenation index, ventilatory ratio, PEEP, minute-ventilation, hemodynamic measures, patients alive and ventilator-free by day-7, and mortality. RESULTS: Of 81 ARDS patients, 34 (42%) and 47 (58%) were randomized to angiotensin-II or placebo, respectively. In angiotensin-II patients, mean P:F increased from 155 mmHg (SD: 69) at baseline to 265 mmHg (SD: 160) at hour-48 compared with no change with placebo (148 mmHg (SD: 63) at baseline versus 164 mmHg (SD: 74) at hour-48)(baseline-adjusted difference: + 98.4 mmHg [95%CI 35.2-161.5], p = 0.0028). Similarly, oxygenation index decreased by - 6.0 cmH2O/mmHg at hour-48 with angiotensin-II versus - 0.4 cmH2O/mmHg with placebo (baseline-adjusted difference: -4.8 cmH2O/mmHg, [95%CI - 8.6 to - 1.1], p = 0.0273). There was no difference in PEEP, minute ventilation, or ventilatory ratio. Twenty-two (64.7%) angiotensin-II patients had sustained hemodynamic response to treatment at hour-3 versus 17 (36.2%) placebo patients (absolute risk-difference: 28.5% [95%CI 6.5-47.0%], p = 0.0120). At day-7, 7/34 (20.6%) angiotensin-II patients were alive and ventilator-free versus 5/47(10.6%) placebo patients. Day-28 mortality was 55.9% in the angiotensin-II group versus 68.1% in the placebo group. CONCLUSIONS: In post-hoc analysis of the ATHOS-3 trial, angiotensin-II was associated with improved oxygenation versus placebo among patients with ARDS and catecholamine-refractory vasodilatory shock. These findings provide a physiologic rationale for trials of angiotensin-II as treatment for ARDS with vasodilatory shock. TRIAL REGISTRATION: ClinicalTrials.Gov Identifier: NCT02338843 (Registered January 14th 2015).

The renin-angiotensin system (RAS) plays a crucial role in regulating blood pressure and the cardio-renal system. The classical RAS, mainly mediated by angiotensin I, angiotensin-converting enzyme, and angiotensin II, has been reported to be altered in critically ill patients, such as those in vasodilatory shock. However, recent research has highlighted the role of some components of the counterregulatory axis of the classical RAS, termed the alternative RAS, such as angiotensin-converting Enzyme 2 (ACE2) and angiotensin-(1-7), or peptidases which can modulate the RAS like dipeptidyl-peptidase 3, in many critical situations. In cases of shock, dipeptidyl-peptidase 3, an enzyme involved in the degradation of angiotensin and opioid peptides, has been associated with acute kidney injury and mortality and preclinical studies have tested its neutralization. Angiotensin-(1-7) has been shown to prevent septic shock development and improve outcomes in experimental models of sepsis. In the context of experimental acute lung injury, ACE2 activity has demonstrated a protective role, and its inactivation has been associated with worsened lung function, leading to the use of active recombinant human ACE2, in preclinical and human studies. Angiotensin-(1-7) has been tested in experimental models of acute lung injury and in a recent randomized controlled trial for patients with COVID-19 related hypoxemia. Overall, the alternative RAS appears to have a role in the pathogenesis of disease in critically ill patients, and modulation of the alternative RAS may improve outcomes. Here, we review the available evidence regarding the methods of analysis of the RAS, pathophysiological disturbances of this system, and discuss how therapeutic manipulation may improve outcomes in the critically ill.

Objective To investigate the changes of angiotensin-converting enzyme （ACE） and angiotensin-converting enzyme 2 （ACE2） levels in children with severe Mycoplasma pneumoniae pneumonia （SMPP） and evaluates their clinical values in predicting the severity of SMPP. Methods A total of 71 children with Mycoplasma pneumoniae pneumonia （MPP group） and 63 with severe Mycoplasma pneumoniae pneumonia （SMPP group） admitted to the Second Hospital of Lanzhou University from October 2020 to December 2023 were recruited in this study. Additionally， 20 healthy children undergoing routine health check-ups during this period were selected as the control group. The serum concentrations of ACE and ACE2 in the three groups were measured using the enzyme-linked immunosorbent assay （ELISA）， and laboratory test results were collected for comparison and correlation analysis between the MPP and SMPP groups. The receiver operating characteristic （ROC） curve was delineated to assess the predictive values of one single index or combined for SMPP. Results In the three groups， the serum ACE level was the highest in the SMPP group and the lowest in the healthy control group. The serum ACE2 level was the highest in the MPP group and the lowest in the healthy control group （all P < 0.008）. Compared to the MPP group， the SMPP group exhibited significantly elevated white blood cell count （WBC）， neutrophil percentage （NE%）， C-reactive protein （CRP）， serum amyloid A protein （SAA）， procalcitonin （PCT）， interleukin-6 （IL-6）， erythrocyte sedimentation rate （ESR）， and D-dimer （all P < 0.001） and these indexes were positively correlated with ACE levels （all P < 0.05）， but negatively correlated with ACE2 levels （all P < 0.05）. The lymphocyte percentage （LY%） was significantly reduced （P < 0.001）， which was positively correlated with ACE2 levels （P < 0.05）， whereas negatively correlated with ACE levels （P < 0.05）. Lactate dehydrogenase （LDH） was elevated （P < 0.05）， which was negatively correlated with ACE2 levels （P < 0.05）， but not correlated with ACE levels （P > 0.05）. The monocyte percentage （MO%） showed neither significant difference nor correlation （both P > 0.05）. ROC curve analysis revealed that ACE， ACE2， CRP， D-dimer， LDH， and combined detection of ACE+ACE2， CRP+D-dimer+LDH all had predictive values for SMPP. Among them， the combined detection of ACE+ACE2 showed the highest predictive value， with an AUC of 0.991 and 95% CI： 0.981-1.000. Conclusion The levels of ACE and ACE2 are likely associated with the onset and progression of SMPP in children， and both ACE and ACE2 serve as good indicators for predicting SMPP.

BackgroundThe effects of the renin-angiotensin-aldosterone system in cardiovascular system have been described based on small studies. The aim of this study was to evaluate the relationship between aldosterone and plasma renin activity (PRA) and cardiovascular structure and function.MethodsWe studied a random sample of Multi-Ethnic Study of Atherosclerosis participants who had aldosterone and PRA blood assays at 2003-2005 and underwent cardiac magnetic resonance at 2010. Participants taking angiotensin-converting enzyme inhibitors or angiotensin receptor blockers were excluded.ResultsThe aldosterone group was composed by 615 participants, mean age 61.6 ± 8.9 years, while the renin group was 580 participants, mean age 61.5 ± 8.8 years and both groups had roughly 50% females. In multivariable analysis, 1 SD increment of log-transformed aldosterone level was associated with 0.07 g/m2 higher left ventricle (LV) mass index (P = 0.04) and 0.11 ml/m2 higher left atrium (LA) minimal volume index (P < 0.01). Additionally, higher log-transformed aldosterone was associated with lower LA maximum strain and LA emptying fraction (P < 0.01). Aldosterone levels were not significantly associated with aortic measures. Log-transformed PRA was associated with lower LV end diastolic volume index (β standardized = 0.08, P = 0.05). PRA levels were not significantly associated with LA and aortic structural or functional differences.ConclusionsHigher levels of aldosterone and PRA are associated with concentric LV remodeling changes. Moreover, aldosterone was related to deleterious LA remodeling changes.

Background The best medical therapy to control hypertension following abdominal aortic aneurysm repair is yet to be determined. We therefore examined whether treatment with renin-angiotensin-aldosterone system inhibitors (RAASIs) versus beta blockers influenced postoperative and 1-year clinical end points following abdominal aortic aneurysm repair in a Medicare-linked database. Methods and Results All patients with hypertension undergoing endovascular aneurysm repair and open aneurysm repair in the Vascular Quality Initiative Vascular Implant Surveillance and Interventional Outcomes Network database between 2003 and 2018 were included. Patients were divided into 2 groups based on their preoperative and discharge medications, either RAASIs or beta blockers. Our cohort included 8789 patients, of whom 3523 (40.1%) were on RAASIs, and 5266 (59.9%) were on beta blockers. After propensity score matching, there were 3053 matched pairs of patients in each group. After matching, RAASI use was associated with lower risk of postoperative mortality (odds ratio [OR], 0.3 [95% CI, 0.1-0.6]), myocardial infarction (OR, 0.1 [95% CI, 0.03-0.6]), and nonhome discharge (OR, 0.6 [95% CI, 0.5-0.7]). Before propensity score matching, RAASI use was associated with lower 1-year mortality (hazard ratio [HR], 0.4 [95% CI, 0.4-0.5]) and lower risk of aneurysmal rupture (HR, 0.7 [95% CI, 0.5-0.9]). These results persisted after propensity score matching for mortality (HR, 0.4 [95% CI, 0.4-0.5]) and aneurysmal rupture (HR, 0.7 [95% CI, 0.5-0.9]). Conclusions In this large contemporary retrospective cohort study, RAASI use was associated with favorable postoperative outcomes compared with beta blockers. It was also associated with lower mortality and aneurysmal rupture at 1 year of follow-up.

Patients with chronic kidney disease (CKD) bear a significant financial burden and face numerous complications and higher mortality rates. The progression of CKD is associated with glomerular injury caused by glomerular hyperfiltration and oxidative stress. Factors such as uncontrolled hypertension, elevated urine protein levels, anemia, and underlying glomerular disease, contribute to CKD progression. In addition to conservative treatment, several medications are available to combat the progression of CKD to end-stage kidney disease. Renin-angiotensin-aldosterone system blockers could slow the progression of CKD by reducing glomerular hyperfiltration, lowering blood pressure, and decreasing inflammation. Mineralocorticoid receptor antagonists inhibit the mineralocorticoid receptor signaling pathway, thereby attenuating inflammation and fibrosis. Sodium-glucose cotransporter 2 inhibitors exhibit protective effects on the kidneys and against cardiovascular events. Tolvaptan, a selective vasopressin V2-receptor antagonist, decelerates the rate of increase in total kidney volume and deterioration of kidney function in patients with rapidly progressive autosomal dominant polycystic kidney disease. The protective effects of AST-120 remain controversial. Due to a lack of evidence regarding the efficacy and safety of these medications in children, it is imperative to weigh the benefits and adverse effects carefully. Further research is essential to establish the efficacy and safety profiles in pediatric populations.

Abstract Background Dipeptidyl peptidase 3 (DPP3) is a ubiquitous cytosolic enzyme released into the bloodstream after tissue injury, that can degrade angiotensin II. High concentrations of circulating DPP3 (cDPP3) have been associated with worse outcomes during sepsis. The aim of this study was to assess the effect of Procizumab (PCZ), a monoclonal antibody that neutralizes cDPP3, in an experimental model of septic shock. Methods In this randomized, open-label, controlled study, 16 anesthetized and mechanically ventilated pigs with peritonitis were randomized to receive PCZ or standard treatment when the mean arterial pressure (MAP) dropped below 50 mmHg. Resuscitation with fluids, antimicrobial therapy, peritoneal lavage, and norepinephrine was initiated one hour later to maintain MAP between 65–75 mmHg for 12 h. Hemodynamic variables, tissue oxygenation indices, and measures of organ failure and myocardial injury were collected. Organ blood flow was assessed using isotopic assessment (99mtechnetium albumin). cDPP3 activity, equilibrium analysis of the renin–angiotensin system and circulating catecholamines were measured. Tissue mRNA expression of interleukin-6 and downregulation of adrenergic and angiotensin receptors were assessed on vascular and myocardial samples. Results PCZ-treated animals had reduced cDPP3 levels and required less norepinephrine and fluid than septic control animals for similar organ perfusion and regional blood flow. PCZ-treated animals had less myocardial injury, and higher PaO2/FiO2 ratios. PCZ was associated with lower circulating catecholamine levels; higher circulating angiotensin II and higher angiotensin II receptor type 1 myocardial protein expression, and with lower myocardial and radial artery mRNA interleukin-6 expression. Conclusions In an experimental model of septic shock, PCZ administration was associated with reduced fluid and catecholamine requirements, less myocardial injury and cardiovascular inflammation, along with preserved angiotensin II signaling. Graphical Abstract

Abstract Aims Regulation of the renin‐angiotensin system (RAS) in heart failure (HF) with reduced ejection fraction (HFrEF) still raises questions, as a large proportion of patients show normal renin levels despite manifest disease. Experimental venous congestion results in reduced renal perfusion pressure and stimulates renin secretion. We hypothesized that excess renin levels are mainly a result of right ventricular failure as a sequalae of left ventricular dysfunction. The study aimed to link right ventricular function (RVF) with renin levels and to investigate further contributors to excess RAS activation. Methods and results Three hundred thirty‐two chronic HFrEF patients undergoing routine ambulatory care were consecutively enrolled in a prospective, registry‐based, observational study. Laboratory parameters, including cardiac‐specific markers renin, aldosterone, and N‐terminal pro‐brain natriuretic peptide (NT‐proBNP), echocardiographic examination (n = 247), and right heart catheterization (n = 85), were documented. The relationship between renin and its respective parameters was analysed. Renin concentration was not associated with the New York Heart Association class or NT‐proBNP. Systolic blood pressure, systemic vascular resistance, serum sodium, aldosterone, and lactate dehydrogenase were associated with increased renin levels (P

Previous studies on renin-angiotensin-aldosterone system (RAAS) mainly focus on renin, prorenin and prorenin receptor (PRR), which play an important role in cardiovascular, renal and other diseases. The physiological function of PRR has been widely studied. Soluble prorenin receptor (sPRR) is generated by cleavage of extracellular components of PRR by protease and secreted into extracellular space, therefore the change of sPRR level may reflect the change of RAAS in tissue. However, there are limited clinical researchs on sPRR. In recent years, increasing evidences show that sPRR has important biological functions in various pathophysiological processes. This article summarized the recent advances in sPRR in cardiovascular system, kidney diseases, respiratory diseases, endocrine and metabolic diseases, pregnancy complications and cancers, and considered that sPRR may be a new biomarker of multiple diseases, and has potential therapeutic effects on metabolic diseases.

Objective(s): Pulmonary arterial hypertension (PAH) is a severe and often fatal disease that is associated with oxidative stress and inflammation. Alamandine, a component of the renin-angiotensin system, known for its antioxidative, anti-inflammatory, and antifibrotic effects, has been investigated in this study to determine if it has protective effects against PAH induced by monocrotaline (MCT) and if these effects are associated with oxidative stress, inflammatory factors, and inducible nitric oxide synthase (iNOS).Materials and Methods: Rats were administered MCT (40 mg/kg) on day 0 and then received alamandine (50 mg/kg/day) via mini-osmotic pumps for 21 days starting one day later. Hemodynamic parameters, electrocardiograms, superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), inflammatory cytokines (TNF-α, IL-1β, and NF-κB), iNOS, and MrgD receptor expression in lung tissue were evaluated at the end of the 21-day period. The MrgD receptor was quantified through immunofluorescent staining, and the histopathology of lung tissues was evaluated using hematoxylin and eosin staining. Results: The results showed that alamandine treatment significantly improved hemodynamic parameters, oxidative stress markers, inflammatory factors, and electrocardiographic data. Furthermore, treatment with alamandine decreased the levels of iNOS. Additionally, alamandine treatment decreased the expression levels of MrgD receptors in the lung tissue of MCT-induced PAH. Conclusion: In summary, this study indicates that alamandine has protective effects against monocrotaline-induced PAH, and these effects may be attributed to the inhibition of oxidative stress, inflammatory parameters, and iNOS.

Muscle atrophy due to limb immobilization and inactivity is a common consequence of many diseases and treatment processes. One of the systems activated in inflammatory conditions is the renin-angiotensin system (RAS). The present study was conducted with the aim of investigating the effects of one of the angiotensin-converting enzyme (ACE) inhibitors, enalapril, on improving muscle atrophy caused by immobility. The study was conducted in three groups: a control, an atrophy, and an atrophy group treated with enalapril on Balb/c mice. After tying a splint to cause atrophy in one of the legs, daily treatment with enalapril intraperitoneally (dissolved in DMSO) at a dose of 10 mg/kg/day was done for 7 days. On the eighth day, the splint was opened and half of the mice were evaluated. Then, in the recovery phase, treatment with enalapril was continued in the remaining mice for 10 days without a splint. At the end of each phase, the mice were examined for the muscle strength of the lower limb muscles, and histological and biochemical analyses were subsequently carried out. The tissue level of the oxidative stress index MDA was evaluated, which showed a significantly lower level in the enalapril group compared to the atrophy group (*P

Background: The impact of renin-angiotensin system inhibitors (RASIs) on the outcome of hypertensive cancer patients undergoing immune checkpoint inhibitor (ICIs) therapy remains ambiguous. This investigation sought to elucidate the consequences of RASIs use on the prognosis for this specific patient group within the context of ICIs treatment, aspiring to provide a clearer basis for rational, evidence-driven choices in the clinical prescription of these medications. Methods: A comprehensive search was conducted on PubMed, Embase, Web of Science, and the Cochrane Library for original studies published up to 6 August 2023. Studies published in English reporting hazard ratios (HRs) with 95% confidence intervals (CIs) for overall survival (OS) and/or progression-free survival (PFS) were included. All statistical analyses were executed utilizing R software (version 4.2.2). Results: A total of 13 studies, encompassing approximately 12,595 patients, satisfied the inclusion criteria. Meta-analyses demonstrated a statistically significant association between the use of RASIs and a favorable outcome in OS (HR, 0.74; 95% CI, 0.62–0.88) and PFS (HR, 0.77; 95% CI, 0.62–0.96) among cancer patients receiving ICIs treatment. Conclusion: This investigation provides compelling evidence supporting the beneficial prognostic impact of RASIs on cancer patients receiving ICIs. RASIs present a viable option as antihypertensive agents for cancer patients with hypertension undergoing ICIs treatment. Further exploration and validation through prospective studies are necessary to establish definitive guidelines for the use of RASIs in managing hypertensive cancer patients undergoing immunotherapy with ICIs. [ABSTRACT FROM AUTHOR]

Recent years have seen a resurgence of interest for the renin–angiotensin–aldosterone system in critically ill patients. Emerging data suggest that this vital homeostatic system, which plays a crucial role in maintaining systemic and renal hemodynamics during stressful conditions, is altered in septic shock, ultimately leading to impaired angiotensin II—angiotensin II type 1 receptor signaling. Indeed, available evidence from both experimental models and human studies indicates that alterations in the renin–angiotensin–aldosterone system during septic shock can occur at three distinct levels: 1. Impaired generation of angiotensin II, possibly attributable to defects in angiotensin-converting enzyme activity; 2. Enhanced degradation of angiotensin II by peptidases; and/or 3. Unavailability of angiotensin II type 1 receptor due to internalization or reduced synthesis. These alterations can occur either independently or in combination, ultimately leading to an uncoupling between the renin–angiotensin–aldosterone system input and downstream angiotensin II type 1 receptor signaling. It remains unclear whether exogenous angiotensin II infusion can adequately address all these mechanisms, and additional interventions may be required. These observations open a new avenue of research and offer the potential for novel therapeutic strategies to improve patient prognosis. In the near future, a deeper understanding of renin–angiotensin–aldosterone system alterations in septic shock should help to decipher patients' phenotypes and to implement targeted interventions. [ABSTRACT FROM AUTHOR]

The renin–angiotensin system (RAS)—a classical blood pressure regulator—largely contributes to healthy organ development and function. Besides, RAS activation promotes age‐related changes and age‐associated diseases, which are attenuated/abolished by RAS‐blockade in several mammalian species. RAS‐blockers also increase rodent lifespan. In previous work, we discussed how RAS‐blockade downregulates mTOR and growth hormone/IGF‐1 signaling, and stimulates AMPK activity (together with klotho, sirtuin, and vitamin D‐receptor upregulation), and proposed that at least some of RAS‐blockade's aging benefits are mediated through regulation of these intermediaries and their signaling to mitochondria. Here, we included RAS‐blockade's impact on other aging regulatory pathways, that is, TGF‐ß, NF‐kB, PI3K, MAPK, PKC, Notch, and Wnt, all of which affect mitochondria. No direct evidence is available on RAS/RAS‐blockade‐aging regulatory pathway–mitochondria interactions. However, existing results allow to conjecture that RAS‐blockers neutralize mitochondrial dysfunction by acting on the discussed pathways. The reviewed evidence led us to propose that the foundation is laid for conducting clinical trials aimed at testing whether angiotensin‐converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB)—even at subclinical doses—offer the possibility to live longer and in better health. As ACEi and ARB are low cost and well‐tolerated anti‐hypertension therapies in use for over 35 years, investigating their administration to attenuate/prevent aging effects seems simple to implement. [ABSTRACT FROM AUTHOR]

Parkinson disease (PD) is one of the most common neurodegenerative diseases of the brain. Of note, brain renin‐angiotensin system (RAS) is intricate in the PD neuropathology through modulation of oxidative stress, mitochondrial dysfunction and neuroinflammation. Therefore, modulation of brain RAS by angiotensin receptor blockers (ARBs) and angiotensin‐converting enzyme inhibitors (ACEIs) may be effective in reducing the risk and PD neuropathology. It has been shown that all components including the peptides and enzymes of the RAS are present in the different brain areas. Brain RAS plays a critical role in the regulation of memory and cognitive function, and in the controlling of central blood pressure. However, exaggerated brain RAS is implicated in the pathogenesis of different neurodegenerative diseases including PD. Two well‐known pathways of brain RAS are recognized including; the classical pathway which is mainly mediated by AngII/AT1R has detrimental effects. Conversely, the non‐classical pathway which is mostly mediated by ACE2/Ang1‐7/MASR and AngII/AT2R has beneficial effects against PD neuropathology. Exaggerated brain RAS affects the viability of dopaminergic neurons. However, the fundamental mechanism of brain RAS in PD neuropathology was not fully elucidated. Consequently, the purpose of this review is to disclose the mechanistic role of RAS in in the pathogenesis of PD. In addition, we try to revise how the ACEIs and ARBs can be developed for therapeutics in PD. [ABSTRACT FROM AUTHOR]

Background: About 10-20% of pancreas allografts are still lost in the early postoperative period despite the identification of numerous detrimental risk factors that correlate with graft thrombosis. Methods: We conducted a multicenter study including 899 pancreas transplant recipients between 2000 and 2018. Early pancreas failure due to complete thrombosis, long-term pancreas, kidney and patient survivals were analyzed and adjusted to donor, recipient and perioperative variables using a multivariate cause-specific Cox model stratified to transplant centers. Results: Pancreas from donors with history of hypertension (6.7%), as well as with high body mass index (BMI), were independently associated with an increased risk of pancreas failure within the first 30 post-operative days (respectively, HR= 2.57, 95% CI from 1.35 to 4.89 and HR= 1.11, 95% CI from 1.04 to 1.19). Interaction term between hypertension and BMI was negative. Donor hypertension also impacted long-term pancreas survival (HR= 1.88, 95% CI from 1.13 to 3.12). However, when pancreas survival was calculated after the postoperative day 30, donor hypertension was no longer a significant risk factor (HR= 1.22, 95% CI from 0.47 to 3.15). A lower pancreas survival was observed in patients receiving a pancreas from a hypertensive donor without RAAS (Renin Angiotensin Aldosterone System) blockers compared to others (50% vs 14%, p < 0.001). Pancreas survival was similar among non-hypertensive donors and hypertensive ones under RAAS blockers. Conclusion: Donor hypertension was a significant and independent risk factor of pancreas failure. The well-known pathogenic role of renin-angiotensin-aldosterone system seems to be involved in the genesis of this immediate graft failure. [ABSTRACT FROM AUTHOR]

Background: Dipeptidyl peptidase 3 (DPP3) is a ubiquitous cytosolic enzyme released into the bloodstream after tissue injury, that can degrade angiotensin II. High concentrations of circulating DPP3 (cDPP3) have been associated with worse outcomes during sepsis. The aim of this study was to assess the effect of Procizumab (PCZ), a monoclonal antibody that neutralizes cDPP3, in an experimental model of septic shock. Methods: In this randomized, open-label, controlled study, 16 anesthetized and mechanically ventilated pigs with peritonitis were randomized to receive PCZ or standard treatment when the mean arterial pressure (MAP) dropped below 50 mmHg. Resuscitation with fluids, antimicrobial therapy, peritoneal lavage, and norepinephrine was initiated one hour later to maintain MAP between 65–75 mmHg for 12 h. Hemodynamic variables, tissue oxygenation indices, and measures of organ failure and myocardial injury were collected. Organ blood flow was assessed using isotopic assessment (99mtechnetium albumin). cDPP3 activity, equilibrium analysis of the renin–angiotensin system and circulating catecholamines were measured. Tissue mRNA expression of interleukin-6 and downregulation of adrenergic and angiotensin receptors were assessed on vascular and myocardial samples. Results: PCZ-treated animals had reduced cDPP3 levels and required less norepinephrine and fluid than septic control animals for similar organ perfusion and regional blood flow. PCZ-treated animals had less myocardial injury, and higher PaO2/FiO2 ratios. PCZ was associated with lower circulating catecholamine levels; higher circulating angiotensin II and higher angiotensin II receptor type 1 myocardial protein expression, and with lower myocardial and radial artery mRNA interleukin-6 expression. Conclusions: In an experimental model of septic shock, PCZ administration was associated with reduced fluid and catecholamine requirements, less myocardial injury and cardiovascular inflammation, along with preserved angiotensin II signaling. [ABSTRACT FROM AUTHOR]

The renin–angiotensin system (RAS) is a complex homeostatic entity with multiorgan systemic and local effects. Traditionally, RAS works in conjunction with the kidney to control effective arterial circulation, systemic vascular resistance, and electrolyte balance. However, chronic hepatic injury and resulting splanchnic dilation may disrupt this delicate balance. The role of RAS in liver disease, however, is even more extensive, modulating hepatic fibrosis and portal hypertension. Recognition of an alternative RAS pathway in the past few decades has changed our understanding of RAS in liver disease, and the concept of opposing vs. "rebalanced" forces is an ongoing focus of research. Whether RAS inhibition is beneficial in patients with chronic liver disease appears to be context-dependent, but further study is needed to optimize clinical management and reduce organ-specific morbidity and mortality. This review presents the current understanding of RAS in liver disease, acknowledges areas of uncertainty, and describes potential areas of future investigation. [ABSTRACT FROM AUTHOR]

Patients with chronic kidney disease (CKD) bear a significant financial burden and face numerous complications and higher mortality rates. The progression of CKD is associated with glomerular injury caused by glomerular hyperfiltration and oxidative stress. Factors such as uncontrolled hypertension, elevated urine protein levels, anemia, and underlying glomerular disease, contribute to CKD progression. In addition to conservative treatment, several medications are available to combat the progression of CKD to end-stage kidney disease. Renin-angiotensin-aldosterone system blockers could slow the progression of CKD by reducing glomerular hyperfiltration, lowering blood pressure, and decreasing inflammation. Mineralocorticoid receptor antagonists inhibit the mineralocorticoid receptor signaling pathway, thereby attenuating inflammation and fibrosis. Sodium-glucose cotransporter 2 inhibitors exhibit protective effects on the kidneys and against cardiovascular events. Tolvaptan, a selective vasopressin V2-receptor antagonist, decelerates the rate of increase in total kidney volume and deterioration of kidney function in patients with rapidly progressive autosomal dominant polycystic kidney disease. The protective effects of AST-120 remain controversial. Due to a lack of evidence regarding the efficacy and safety of these medications in children, it is imperative to weigh the benefits and adverse effects carefully. Further research is essential to establish the efficacy and safety profiles in pediatric populations. [ABSTRACT FROM AUTHOR]

Obesity has emerged as a significant public health challenge. With the ongoing increase in life expectancy, the prevalence of obesity is steadily growing, particularly among older age demographics. The extension of life expectancy frequently results in additional years of vulnerability to chronic health issues associated with obesity in the elderly. The concept of SARS-CoV-2 directly infecting adipose tissue stems from the fact that both adipocytes and stromal vascular fraction cells express ACE2, the primary receptor facilitating SARS-CoV-2 entry. It is noteworthy that adipose tissue demonstrates ACE2 expression levels similar to those found in the lungs within the same individual. Additionally, ACE2 expression in the adipose tissue of obese individuals surpasses that in non-obese counterparts. Viral attachment to ACE2 has the potential to disturb the equilibrium of renin-angiotensin system homeostasis, leading to an exacerbated inflammatory response. Consequently, adipose tissue has been investigated as a potential site for active SARS-CoV-2 infection, suggesting its plausible role in virus persistence and contribution to both acute and long-term consequences associated with COVID-19. This review is dedicated to presenting current evidence concerning the presence of SARS-CoV-2 in the adipose tissue of elderly individuals infected with the virus. Both obesity and aging are circumstances that contribute to severe health challenges, heightening the risk of disease and mortality. We will particularly focus on examining the mechanisms implicated in the long-term consequences, with the intention of providing insights into potential strategies for mitigating the aftermath of the disease. [ABSTRACT FROM AUTHOR]