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Background Cardiac injury caused by iron overload is the leading cause of mortality and morbidity in patients with beta-thalassemia, owing to frequent blood transfusion, increased iron overload, and blood hemolysis. Objective This research aimed to assess several novel cardiac biomarkers in the blood samples of children and adult patients with beta-thalassemia major (βTM), along with their respective control groups. These biomarkers included endothelin 1 (ET-1), N-terminal pro-brain natriuretic peptide (NT-proBNP), atrial natriuretic peptide (ANP), growth differentiation factor-15 (GDF-15), and renalase (RNLS). Methods This case-control study was done on 46 patients with βTM (23 children <18 years, and 23 adults ≥18 years) from the Genetic Hematology Center in Thi-Qar province, Iraq, and 42 comparable controls in 2 groups (21 for each group) in the period from February to April 2023. Results Levels of ET-1, NT-proBNP, ANP, GDF-15, RNLS, and ferritin were higher in the children and adults with βTM than in the control subjects. Conclusion Elevations of the novel cardiac biomarkers ET-1, NT-proBNP, ANP, GDF-15, and RNLS in the sera of children and adult patients with βTM when compared with comparable control subjects confirm that the majority of patients with βTM are at risk of cardiac and cardiovascular complications even when there are no obvious symptoms, especially in children, which gives suitable predictive biomarkers. [ABSTRACT FROM AUTHOR]

Objective: The endothelial glycocalyx layer (EGL) is the interface between the blood and the endothelium that regulates permeability. This study compared the effects of liberal and restrictive fluid therapies on atrial natriuretic peptide (ANP) release and EGL products in radical cystectomy surgery. We hypothesized that a liberal regimen would damage the glycocalyx layer, resulting in a higher serum EGL product concentration than restrictive therapy. Materials and Methods: Patients were randomized into two groups for restrictive (group R) or liberal (group L) regimens. Group R received 2 mL/kg/h Ringer’s lactate and 2 mcg/kg/h norepinephrine infusion, whereas group L received only Ringer’s lactate infusion at 10 mL/kg/h rate during the surgery. Preoperative and postoperative blood samples were obtained to evaluate ANP levels and glycocalyx degradation products. The stroke volume index, cardiac index, stroke volume variation, and systemic vascular resistance index parameters were recorded at 30-min intervals throughout the surgery. The length of stay in the hospital and intensive care unit and postoperative complications were recorded. Results: The study was completed with 39 patients. Postoperative ANP levels were higher in group L in both between- and within group examination (p<0.05). EGL constituents; syndecan-1 and hyaluronan concentrations, were higher in group L (p<0.05). Advanced hemodynamic parameters indicated insignificant changes between the groups (p>0.05). Postoperative complications and length of stay data were similar (p>0.05). Conclusion: ANP, hyaluronan, and syndecan-1 concentrations can be used as an indirect measurement method to show EGL damage and hypervolemia in major urologic surgeries. Advanced hemodynamic monitoring was ineffective for confirming hypervolemia. [ABSTRACT FROM AUTHOR]

Diabetic cardiomyopathy, a severe diabetic complication, impairs heart function, leading to heart failure. Treatment that effectively addresses this condition without causing side effects is urgently needed. Current anti-hyperglycemic therapies are expensive, has side effects and do not effectively prevent cardiac remodeling. Therefore, it is important to explore natural products that may have the potential to reverse cardiac remodeling. That is why the aim of the current study was to determine the left ventricular remodeling potential of the methanolic extract of Artemisia vulgaris in a diabetic cardiomyopathy rat model. Following the initial comprehensive phytochemical evaluation of plant phenolic and flavonoid content, which showed strong anti-hyperglycemic and antioxidant activities, an extract of Artemisia vulgaris was administered in an in vivo experiment. Diabetic cardiomyopathy was induced in Wistar albino rats according to previously described protocols in the literature, and the effect of treatment was checked by serum and histopathological analysis after 45 days. Artemisia vulgaris treatment significantly (p ≤ 0.05) reduced fasting blood glucose (108.5 ± 1.75 mg/dL), glycated hemoglobin (4.03 ± 0.12 %), serum glucose (116.66 ± 3.28 mg/dL), insulin (15.66 ± 0.66 ng/mL), total oxidant status (54.66 ± 3.22 µmol H2O2Equiv.L−1), Malondialdehyde (0.20 ± 0.01 mmol/L), total cholesterol (91.16 ± 3.35 mg/dL), triglycerides (130.66 ± 3.15 mg/dL), low-density lipids (36.57 ± 1.02 mg/dL), sodium (140 ± 3.21 mmol/L), calcium (10.44 ± 0.24 mmol/L), creatine kinase MB (1227.5 ± 17.89 IU/L), lactate dehydrogenase (1300 ± 34.64 IU/L), C-reactive protein (30 ± 0.57 pg/mL), tumor necrosis factor-α (58.66 ± 1.76 pg/mL), atrial natriuretic peptide (2.53 ± 0.04 pg/mL), B-type natriuretic peptide (10.66 ± 0.44 pg/mL), aspartate aminotransferase (86.5 ± 4.99 U/L), Alanine Transaminase (55.33 ± 2.90 U/L), urea (25.33 ± 1.15 mg/dL) and creatinine (0.64 ± 0.02 mg/dL) but significantly increased (p ≤ 0.05) total antioxidant capacity (1.73 ± 0.07 mmol Trolox Equil./L), high-density lipids (40 ± 1.59 mg/dL) and potassium (3.82 ± 0.04 mmol/L) levels. ECG and histopathology confirmed the significant improvement in remodeling and the reversal of structural changes in the heart and pancreas. In conclusion, Artemisia vulgaris possesses significant left ventricular remodeling potential in course of diabetes-induced cardiomyopathy. [ABSTRACT FROM AUTHOR]

Left-to-right differences in the histopathologic patterns of transthyretin-derived amyloid (ATTR) deposition in the atria of older adults have not yet been investigated. Hence, this study evaluated heart specimens from 325 serial autopsy subjects. The amount of ATTR deposits in the seven cardiac regions, including both sides of atria and atrial appendages, was evaluated semiquantitatively. Using digital pathology, we quantitatively evaluated the immunohistochemical deposition burden of ATTR in the myocardium. We identified 20 sporadic ATTR cardiac amyloidosis cases (nine males). All patients had ATTR deposition in the left atrial regions of the myocardium. In the semiquantitative analysis, 14 of the 20 cases showed more severe ATTR deposition on the left atrial regions than on the right side, with statistically significant differences in the pathology grading (p < 0.01 for both the atrium and atrial appendage). Quantitative analysis further supported the difference. Moreover, six had ATTR deposition in the epineurium and/or neural fibers of the atria. Cluster analysis revealed that ATTR deposition in the myocardium was significantly more severe in males than in females. The heterogeneous distribution of amyloid deposits between atria revealed in this study may impair the orderly transmission of the cardiac conduction system and induce arrhythmias, which may be further aggravated by additional neuropathy in the advanced phase. This impairment could be more severe among males. These findings emphasize that atrial evaluation is important for individuals with sporadic ATTR cardiac amyloidosis, particularly for early detection. [ABSTRACT FROM AUTHOR]

Introduction: Dimenhydrinate and scopolamine are frequently used drugs, but they cause drowsiness and performance decrement. Therefore, it is crucial to find peripheral targets and develop new drugs without central side effects. This study aimed to investigate the anti-motion sickness action and inner ear-related mechanisms of atrial natriuretic peptide (ANP). Methods: Endolymph volume in the inner ear was measured with magnetic resonance imaging and expression of AQP2 and p-AQP2 was detected with Western blot analysis and immunofluorescence method. Results: Both rotational stimulus and intraperitoneal arginine vasopressin (AVP) injection induced conditioned taste aversion (CTA) to 0.15% sodium saccharin solution and an increase in the endolymph volume of the inner ear. However, intraperitoneal injection of ANP effectively alleviated the CTA behaviour and reduced the increase in the endolymph volume after rotational stimulus. Intratympanic injection of ANP also inhibited rotational stimulus-induced CTA behaviour, but anantin peptide, an inhibitor of ANP receptor A (NPR-A), blocked this inhibitory effect of ANP. Both rotational stimulus and intraperitoneal AVP injection increased the expression of AQP2 and p-AQP2 in the inner ear of rats, but these increases were blunted by ANP injection. In in vitro experiments, ANP addition decreased AVP-induced increases in the expression and phosphorylation of AQP2 in cultured endolymphatic sac epithelial cells. Conclusion: Therefore, the present study suggests that ANP could alleviate motion sickness through regulating endolymph volume of the inner ear increased by AVP, and this action of ANP is potentially mediated by activating NPR-A and antagonising the increasing effect of AVP on AQP2 expression and phosphorylation. [ABSTRACT FROM AUTHOR]

Aims: The link between nocturia and cardiovascular disease (CVD) is frequently discussed in literature, yet the precise nature of this relationship remains poorly characterized. The existing literature was reviewed in order to address issues concerning the origin, diagnosis, management, and implications of the co‐occurrence of CVD and nocturia. Methods: This review summarizes literature and recommendations regarding the link between CVD and nocturia discussed during a think‐tank meeting held at the 2023 International Consultation on Incontinence‐Research Society. Results: Cardiovascular disorders are often underestimated contributors to nocturia, with various potential mechanisms influencing nighttime urination, such as impact on fluid retention, atrial natriuretic peptide, and glomerular filtration rate. The redistribution of fluid from leg edema in supine position can lead nocturnal polyuria (NP). Additionally, sleep disturbances due to nocturia in itself may lead to CVD through an increase in blood pressure, insulin resistance, and inflammation. Disrupted circadian rhythms (e.g., in sleep pattern and urine production) were identified as critical factors in most etiologies of nocturia, and their contribution is deemed imperative in future research and treatment approaches, particularly in the aging population. NP can be detected through a simple bladder diary and can even be used to distinguish cardiac from noncardiac causes of nocturia. For the treatment of NP, desmopressin can be effective in select patients, however, caution and close monitoring is warranted for those with CVD due to increased risk of side effects. Conclusions: Gaps were identified in the available evidence and clear cut recommendations were put forth for future research. It is essential to gain a deeper understanding of the mechanisms linking nocturia and CVD to develop optimal management strategies. [ABSTRACT FROM AUTHOR]

Myocardial infarction is a worldwide disease with high morbidity and mortality and a major cause of chronic heart failure, seriously affecting patients' quality of life. Natural medicine has been used to cure or prevent cardiovascular disease for decades. As a natural flavonoid, anthocyanidin has been used to treat many diseases due to its antioxidative, anti-inflammatory, and other properties. A mouse model (C57BL/6) weighing 30–40 g was utilized to induce myocardial infarction by ligating the left anterior descending coronary artery. Cyanidin (30 mg/kg) was administered orally to mice for four weeks. A variety of assessments were used to evaluate cardiac function. The gene expression was measured using RNAseq and Western blot. Histological changes in myocardial tissue were assessed using staining techniques, including Masson, Hematoxylin Eosin (HE), and transmission electron microscopy. Tunnel staining was implemented as a method to detect cellular apoptosis. For the quantification of B-type natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) in the serum, an enzyme-linked immunosorbent assay (ELISA) was employed. Furthermore, autodock simulation was executed in order to assess the interaction between cyanidin and a subset of genes. Cyanidin treatment inhibited myocardial cell apoptosis, improved cardiac function, and reduced serum concentrations of BNP and atrial natriuretic peptide ANP, as well as mitigated histological cardiac tissue damage. Cyanidin also inhibited the activity of matrix metalloproteinases (MMP2/9) and Fibronectin 1 (Fn1). Cyanidin improves heart function and reduces myocardial damage in mice after MI. Furthermore, cyanidin can prevent cardiomyocyte apoptosis. These effects are most likely caused by suppression of MMP9/2 and control of the Akt signaling pathway, suggesting an appropriate therapeutic target. [ABSTRACT FROM AUTHOR]

Background: The pathogenesis of diabetic cardiomyopathy is closely linked to abnormal glycosylation modifications. N-acetylglucosaminyltransferase V (GnT-V), which catalyzes the production of N-linked -1–6 branching of oligosaccharides, is involved in several pathophysiological mechanisms of many disorders, including cardiac hypertrophy and heart failure. However, the mechanism by which GnT-V regulates cardiac hypertrophy in diabetic cardiomyopathy is currently poorly understood. In this study, we investigated the role of GnT-V on myocardial hypertrophy in diabetic cardiomyopathy and elucidated the underlying mechanisms. Material and methods: Streptozotocin (STZ) was intraperitoneally injected into mice to induce diabetic cardiomyopathy. An adeno-associated virus (AAV) carrying negative control small hairpin RNA (shNC) or GnT-V-specifc small hairpin RNA (shGnT-V) was used to manipulate GnT-V expression. In our study, forty male C57BL/6J mice were randomly divided into four groups (10 mice per group): control mice with AAV-shNC, diabetic cardiomyopathy mice with AAV-shNC, control mice with AAV-shGnT-V, and diabetic cardiomyopathy mice with AAV-shGnT-V. In addition, H9C2 cells and primary neonatal cardiac fibroblasts treated with high glucose were used as a cell model of diabetes. Analysis of cardiac hypertrophy and fibrosis, as well as functional studies, were used to investigate the underlying molecular pathways. Results: AAV-mediated GnT-V silencing dramatically improved cardiac function and alleviated myocardial hypertrophy and fibrosis in diabetic mice. In vitro experiments demonstrated that GnT-V was elevated in cardiomyocytes and induced cardiomyocyte hypertrophy in response to high glucose stimulation. GnT-V knockdown significantly reduced the expression of the integrinβ1 signaling pathway, as evidenced by decreased downstream ERK1/2 activity, which inhibited cardiomyocyte hypertrophy accompanied by reduced ANP, BNP, and β-MHC expression. Furthermore, knocking down GnT-V expression lowered the TGF-β1-Smads signaling pathway, which reduced the expression of α-SMA, collagen I, and collagen III. Conclusions: Overall, our research indicated that GnT-V may be a useful therapeutic target to treat diabetic cardiomyopathy, primarily in the inhibition of myocardial hypertrophy and fibrosis. [ABSTRACT FROM AUTHOR]

The myocardium is a highly oxidative tissue in which mitochondria are essential to supply the energy required to maintain pump function. When pathological hypertrophy develops, energy consumption augments and jeopardizes mitochondrial capacity. We explored the cardiac consequences of chronic swimming training, focusing on the mitochondrial network, in spontaneously hypertensive rats (SHR). Male adult SHR were randomized to sedentary or trained (T: 8-week swimming protocol). Blood pressure and echocardiograms were recorded, and hearts were removed at the end of the training period to perform molecular, imaging, or isolated mitochondria studies. Swimming improved cardiac midventricular shortening and decreased the pathological hypertrophic marker atrial natriuretic peptide. Oxidative stress was reduced, and even more interesting, mitochondrial spatial distribution, dynamics, function, and ATP were significantly improved in the myocardium of T rats. In the signaling pathway triggered by training, we detected an increase in the phosphorylation level of both AKT and glycogen synthase kinase-3 β, key downstream targets of insulin-like growth factor 1 signaling that are crucially involved in mitochondria biogenesis and integrity. Aerobic exercise training emerges as an effective approach to improve pathological cardiac hypertrophy and bioenergetics in hypertension-induced cardiac hypertrophy. [ABSTRACT FROM AUTHOR]

AIM: To investigate the effects of skeletal muscle mass on cardiac structure and function in rats subjected to abdominal aortic constriction (AAC), and to explore its potential mechanisms. METHODS: (1) Thirty male SD rats were randomly divided into 3 groups: control (CON) group (n=10), muscular atrophy (MA) group (n=10), and muscular hypertrophy (MH) group (n=10). The rats in MA group underwent bilateral tibial nerve removal to induce MA, while those in MH group engaged in weight-bearing running to promote MH. Four weeks later, skeletal muscle samples were collected, and indicators of MA and MH were assessed. (2) Another rats after modeling above were divided into 4 groups: CON group (n=10), cardiac pathological remodeling group (AAC group; n=10), MA+AAC group (n=10), and MH+AAC group (n=10). All rats, except those in CON group which underwent a sham operation, received AAC surgery. Four weeks after surgery, cardiac structure and function were assessed by echocardiography, while morphological changes of the soleus and gastrocnemius muscles and myocardium were evaluated by pathological staining. Serum myostatin (MSTN) level was measured using ELISA. The mRNA expression levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in the myocardium, and MSTN in the skeletal muscle and myocardium were detected by real-time PCR. RESULTS: After 4 weeks of either denervation or weight-bearing running, significant atrophy and hypertrophy of the gastrocnemius and soleus muscles were observed in MA and MH groups, respectively, compared with CON group. However, no significant differences were noted in heart weight/body weight ratio, left ventricular end-diastolic wall thickness, ejection fraction, or other related indexes among these groups (P>0. 05). In comparison to AAC group, the rats in MA+AAC group showed a significant increase in heart weight/body weight ratio and left ventricular end-diastolic anterior wall thickness, a decrease in end-diastolic internal diameter, an increase in ejection fraction (P<0. 05 or P<0. 01), and exacerbated myocardial fibrosis. Conversely, in MH+AAC group, there was a significant decrease in heart weight/body weight ratio and left ventricular end-diastolic wall thickness, an increase in end-diastolic internal diameter, and a lower ejection fraction (P<0. 05 or P<0. 01), with reduced myocardial fibrosis. Compared with AAC group, myocardial ANP and BNP mRNA expression significantly increased in MA+AAC group and decreased in MH+AAC group (P<0. 01). Additionally, soleus and gastrocnemius muscle MSTN mRNA expression, myocardial MSTN mRNA expression, and serum MSTN level significantly increased in MA+AAC group (P<0. 01) and significantly decreased in MH+AAC group (P< 0.05). CONCLUSION: Atrophic skeletal muscle exacerbated the pathological remodeling induced by AAC surgery, whereas hypertrophic skeletal muscle mitigated this remodeling. Skeletal muscle mass plays a critical role in cardiac pathological remodeling, with MSTN potentially regulating this process. [ABSTRACT FROM AUTHOR]

The central role of natriuretic peptides (NPs) in the complex cardio‐renal integrated physiology and organ failure has been revealed over the last four decades. Atrial natriuretic peptide (ANP), the oldest representative of the NPs family, is produced through conversion of proANP to the mature peptide by corin, a trans‐membrane protease localized to the cardiac myocyte membrane. Similarly, brain natriuretic peptide (BNP) is generated by furin, which cleaves proBNP to BNP in myocytes. Though the components of NPs system, their synthesis and target organs are well established, understanding their role in the interplay between the heart and the kidney is steadily evolving. In this context, Feldman et al. (New England Journal of Medicine, 389, 1685) recently described patients with hypertension, cardiomyopathy, atrial arrhythmia and left atrial fibrosis, associated with a homozygous loss‐of‐function variant of the gene encoding corin (Cor−/−). Notably, reduced baseline urinary electrolyte and creatinine excretion have been observed in one of the studied patients. This renal excretory functional impairment could be attributed to the lack of cardiac‐derived ANP in these patients, as implied by Feldman et al. Yet, in this mini‐review we suggest that this aberrant renal manifestation may principally stem from lack of local ANP production at renal tissue, as corin is normally expressed in proximal tubules, Henle's loop and collecting ducts, with locally produced ANP provoking Na+ and water exertion. Collectively, it seems that beside the classic well‐established cardio‐renal axis, the renal NPs system functions as local endocrine machinery in the regulation of sodium excretion. [ABSTRACT FROM AUTHOR]

Overhydration and cardiac function abnormalities are common in hemodialysis patients. The association of N-terminal prohormone for brain natriuretic peptide (NT-proBNP) and other fluid status biomarkers with echocardiographic parameters of heart failure with preserved ejection fraction (HFpEF) is scarcely investigated in this population. A total of 100 separate measurements performed in 50 dialysis patients (29 male, aged 60 ± 17 years) in NYHA class II/II and preserved left ventricle ejection fraction were analyzed. Plasma levels of NT-proBNP, mid-regional prohormone for atrial natriuretic peptide (MR-proANP) and copeptin (CPP) were measured. The E/e' ratio as an index of HFpEF and other echocardiographic parameters were calculated. An E/e' ratio >9 was associated with higher median right ventricular systolic pressure (RVSP) and LVMI values. Left atrium volume index (LAVI) as well as NT-proBNP and MR-proANP, but not CPP levels were significantly higher in this group. In a stepwise multivariate analysis, only CPP and IL-6 levels were found to be independently associated with the E/e' ratio in the study group, whereas NT-proBNP and MR-proANP were associated only with left heart structure parameters and LVEF. Of the analyzed biomarkers, only the CPP level was found to be independently associated with the E/e' ratio in maintenance hemodialysis patients. [ABSTRACT FROM AUTHOR]

Sleep deprivation (SD) has emerged as a critical concern impacting human health, leading to significant damage to the cardiovascular system. However, the underlying mechanisms are still unclear, and the development of targeted drugs is lagging. Here, we used mice to explore the effects of prolonged SD on cardiac structure and function. Echocardiography analysis revealed that cardiac function was significantly decreased in mice after five weeks of SD. Real-time quantitative PCR (RT-q-PCR) and Masson staining analysis showed that cardiac remodeling marker gene Anp (atrial natriuretic peptide) and fibrosis were increased, Elisa assay of serum showed that the levels of creatine kinase (CK), creatine kinase-MB (CK-MB), ANP, brain natriuretic peptide (BNP) and cardiac troponin T (cTn-T) were increased after SD, suggesting that cardiac remodeling and injury occurred. Transcript sequencing analysis indicated that genes involved in the regulation of calcium signaling pathway, dilated cardiomyopathy, and cardiac muscle contraction were changed after SD. Accordingly, Western blotting analysis demonstrated that the cardiac-contraction associated CaMKK2/AMPK/cTNI pathway was inhibited. Since our preliminary research has confirmed the vital role of Casein Kinase-2 -Interacting Protein-1 (CKIP-1, also known as PLEKHO1) in cardiac remodeling regulation. Here, we found the levels of the 3' untranslated region of Ckip-1 (Ckip-1 3'UTR) decreased, while the coding sequence of Ckip-1 (Ckip-1 CDS) remained unchanged after SD. Significantly, adenovirus-mediated overexpression of Ckip-1 3'UTR alleviated SD-induced cardiac dysfunction and remodeling by activating CaMKK2/AMPK/cTNI pathway, which proposed the therapeutic potential of Ckip-1 3'UTR in treating SD-induced heart disease. [ABSTRACT FROM AUTHOR]

An angiotensin receptor/neprilysin inhibitor (ARNI), a heart failure treatment, is a combination drug made up of sacubitril, a neprilysin inhibitor, and valsartan, a vascular receptor blocker. No human or veterinary studies regarding the effect of ARNI on renal haemodynamics in the absence of cardiac or renal issues exist. Therefore, we investigated the effect of ARNI on renal haemodynamics in five healthy dogs. ARNI was administered to all five dogs at an oral dose of 20 mg/kg twice daily for 4 weeks. Renal haemodynamics were assessed on the day before ARNI administration (BL), on Day 7, and on Day 28. The glomerular filtration rate (GFR) significantly increased on Day 28 compared to BL and Day 7, whereas renal plasma flow increased on Day 7 and Day 28 compared to BL. Systolic blood pressure significantly decreased between BL and Day 28. Plasma atrial natriuretic peptide (ANP) concentrations increased on Day 7 compared to BL. Additionally, ANP concentrations increased on Day 28 in three of the five dogs. Different ANP concentrations were observed in the remaining two dogs. Both urine output volume and heart rate remained relatively stable and did not exhibit significant change. In conclusion, ARNI may enhance renal haemodynamics in healthy dogs. ARNI could be a valuable drug for treating both heart and kidney disease in dogs. [ABSTRACT FROM AUTHOR]

Aims: Cardiac hypertrophy, an adaptive response of the heart to stress overload, is closely associated with heart failure and sudden cardiac death. This study aimed to investigate the therapeutic effects of chlorogenic acid (CGA) on cardiac hypertrophy and elucidate the underlying mechanisms. Methods and results: To simulate cardiac hypertrophy, myocardial cells were exposed to isoproterenol (ISO, 10 μM). A rat model of ISO‐induced cardiac hypertrophy was also established. The expression levels of cardiac hypertrophy markers, endoplasmic reticulum stress (ERS) markers, and apoptosis markers were measured using quantitative reverse transcription PCR and western blotting. The apoptosis level, size of myocardial cells, and heart tissue pathological changes were determined by terminal deoxynucleotidyl transferase dUTP nick‐end labelling staining, immunofluorescence staining, haematoxylin and eosin staining, and Masson's staining. We found that CGA treatment decreased the size of ISO‐treated H9c2 cells. Moreover, CGA inhibited ISO‐induced up‐regulation of cardiac hypertrophy markers (atrial natriuretic peptide, brain natriuretic peptide, and β‐myosin heavy chain), ERS markers (C/EBP homologous protein, glucose regulatory protein 78, and protein kinase R‐like endoplasmic reticulum kinase), and apoptosis markers (bax and cleaved caspase‐12/9/3) but increased the expression of anti‐apoptosis marker bcl‐2 in a dose‐dependent way (0, 10, 50, and 100 μM). Knockdown of sphingosine‐1‐phosphate receptor 1 (S1pr1) reversed the protective effect of CGA on cardiac hypertrophy, ERS, and apoptosis in vitro (P < 0.05). CGA also restored ISO‐induced inhibition on the AMP‐activated protein kinase (AMPK)/sirtuin 1 (SIRT1) signalling in H9c2 cells, while S1pr1 knockdown abolished these CGA‐induced effects (P < 0.05). CGA (90 mg/kg/day, for six consecutive days) protected rats against cardiac hypertrophy in vivo (P < 0.05). Conclusions: CGA treatment attenuated ISO‐induced ERS and cardiac hypertrophy by activating the AMPK/SIRT1 pathway via modulation of S1pr1. [ABSTRACT FROM AUTHOR]

Atrial natriuretic peptide (ANP) plays a central role in the regulation of blood pressure and volume. ANP activities are mediated by natriuretic peptide receptor‐A (NPR‐A), a single‐pass transmembrane receptor harboring intrinsic guanylate cyclase activity. This study investigated the mechanism underlying NPR‐A‐dependent hormone recognition through the determination of the crystal structures of the NPR‐A extracellular hormone‐binding domain complexed with full‐length ANP, truncated mutants of ANP, and dendroaspis natriuretic peptide (DNP) isolated from the venom of the green Mamba snake, Dendroaspis angusticeps. The bound peptides possessed pseudo‐two‐fold symmetry, despite the lack of two‐fold symmetry in the primary sequences, which enabled the tight coupling of the peptide to the receptor, and evidently contributes to guanylyl cyclase activity. The binding of DNP to the NPR‐A was essentially identical to that of ANP; however, the affinity of DNP for NPR‐A was higher than that of ANP owing to the additional interactions between distinctive sequences in the DNP and NPR‐A. Consequently, our findings provide valuable insights that can be applied to the development of novel agonists for the treatment of various human diseases. [ABSTRACT FROM AUTHOR]

Background: Ftost-operative atrial fibrillation (POAF) is a frequent complication after cardiac surgery. It is associated with prolonged hospital stay, increased morbidity, mortality rate and economic costs. The aim of the study was to determine the association between the values of Galectin-3 and N-terminal pro-B-type natriuretic peptide (NT-proBNP) with POAF after cardiac surgery. Methods: A prospective study enrolled patients aged 18-85 years old admitted due to elective coronary artery bypass graft surgery (CABG) or CABG + aortic valve replacement. The plasma Galectin-3 and NT-proBNP levels were measured one day before surgery postoperative days 1 and 7. Results: The study included a total of 103 patients. POAF was registered in 45 patients. The mean age of patients in whom POAF occurred was 68.8 years, while other patients' mean age was 65.5 years (p= 0.028). Patients with POAF did not differ from the group without POAF in the values of Galectin-3 and NT-proBNP preoperatively as well as on the first and seventh postoperative days. Changes in Galectin-3 levels on the first postoperative day had statistically significant value for predicting POAF (AUC=0.627 [0.509-0.745], p<0.05). Decrease in Galectin-3 level concentration on the first postoperative day over 17% increases the risk of developing AF. Conclusions: Preoperative values of Galectin-3 and NT- proBNP are not associated with POAF development after cardiac surgery. [ABSTRACT FROM AUTHOR]

Many recent studies have validated the internal jugular vein ultrasound (IJV-US) for estimating volemic status in critical patients. If research confirms its accuracy in detecting intravascular volume, congestion, and prognosis, this method could help manage heart failure (HF) because it is simple, fast, and applicable in several settings. This review examines the IJV-US's reliability, diagnostic accuracy, and ability to predict poor outcomes for HF, as well as its correlation with surrogate congestion tests like natriuretic peptides and elevated central venous pressure (CVP). Our systematic review followed the PRISMA statement for systematic reviews and meta-analyses. Eleven studies examined the reliability and validity of IJV-US measures in predicting congestion, volume status, and prognosis in adult spontaneously breathing HF patients. We searched PubMed, Cochrane Library, and EMBASE. IJV-US measurements using Valsalva and sniffing seem more accurate for predicting congestion, volume status, high CVP, and poor prognosis. The IJV ratio in chronic HF and out-hospital patients and the absence of IJV area [cross-sectional area (CSA)] changes in acute HF (AHF) and in-hospital patients are the most validated measurements. No evidence suggests the method is reliable between and within raters. AHF patients' IJV ratio and CSA absence appear to correlate with CVP and atrial natriuretic peptides. In conclusion, the IJV-US may be useful for managing HF patients, but more research is needed to confirm its reliability and prognostic accuracy. Develop a standard US protocol lastly. [ABSTRACT FROM AUTHOR]

We established myocardial injury models in vivo and in vitro to investigate the cardioprotective effect of gomisin D obtained from Schisandra chinensis. Gomisin D significantly inhibited isoproterenol-induced apoptosis and hypertrophy in H9C2 cells. Gomisin D decreased serum BNP, ANP, CK-MB, cTn-T levels and histopathological alterations, and inhibited myocardial hypertrophy in mice. In mechanisms research, gomisin D reversed ISO-induced accumulation of intracellular ROS and Ca2+. Gomisin D further improved mitochondrial energy metabolism disorders by regulating the TCA cycle. These results demonstrated that gomisin D had a significant effect on isoproterenol-induced myocardial injury by inhibiting oxidative stress, calcium overload and improving mitochondrial energy metabolism. [ABSTRACT FROM AUTHOR]

ANP (atrial natriuretic peptide) and BNP (brain natriuretic peptide) are important indicators for detecting heart failure (HF). However, traditional testing method had low real-time detecting and poor sensitivity, which limited the early diagnosis of HF. Herein, we prepare a low cost device based on upconversion microparticles (UCMPs) with porous structure, which has a high detecting sensitivity for ANP and BNP markers. The lowest detection concentration of ANP and BNP can reach 5 pg/mL with Yb/Tm/Sr/12CaO·7Al 2 O 3 (Yb/Tm/Sr/C12A7)-LFS and Yb/Er/Sr/C12A7-LFS, which are of one order lower than their clinical cutoff. The whole UCL intensity of UCMPs enhanced via Sr2+ ions doping. UCMPs not only have dual-color UCL, but also achieve good temperature sensing. The maximum S R of Yb/Tm/Sr/C12A7 and Yb/Er/Sr/C12A7 based on UCL ratio are 4.23 % K−1 and 3.36 % K−1, respectively. The UCMPs-LFS device has a low-cost laser diode, simplified laser and permits a mobile phone camera to collect the imaging, which is benefit for detecting ANP and BNP application. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the role of circSlc8a1 in cardiac hypertrophy (CH), a pathological change in various cardiovascular diseases. Methods: An in vitro CH model was established using angiotensin II (AngII) treated H9c2 cells, followed by western blotting and RT-qPCR for detecting relative expressions. Cell viability and proliferation were analyzed using CCK-8 and EdU assays, while lactate dehydrogenase (LDH), reactive oxygen species (ROS), glutathione (GSH), and iron levels were determined using corresponding kits. Moreover, dual-luciferase reporter and RNA pull-down assays were performed to demonstrate whether miR-673-5p is bound to circSlc8a1 or transferrin receptor (TFRC). Results: The results indicated that the expressions of circSlc8a1 and TFRC were increased, while miR-673-5p was decreased in the AngII treated H9c2 cells. The ferroptosis inhibitor treatment decreased the atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and β-major histocompatibility complex (β-MHC) protein expressions, and circSlc8a1 expressions. Knocking down of circSlc8a1 inhibited promoted the cell viability and proliferation, increased the GSH content, glutathione peroxidase 4, and solute carrier family 7 member 11 protein expressions, and decreased the LDH, ROS, iron levels, and RAS protein expressions. The MiR-673-5p inhibitor antagonized the role of si-circSlc8a1, and the over-expressed TFRC reversed the miR-673-5p mimicking effects in AngII treated H9c2 cells. Conclusion: CircSlc8a1 promoted the ferroptosis in CH via regulating the miR-673-5p/TFRC axis. [ABSTRACT FROM AUTHOR]

This article is an editorial published in Frontiers in Endocrinology that discusses the importance of molecular biomarkers in the diagnosis and prognosis of cardiometabolic disease (CMD). CMD refers to a combination of metabolic and cardiovascular diseases, with insulin resistance playing a central role in its development. The article highlights the challenges in managing CMD due to its diverse manifestations and the absence of reliable molecular biomarkers. The editorial presents nine original research articles that explore potential biomarkers for CMD, including serum low-density lipoprotein receptor-related protein 1 (sLRP1), atrial natriuretic peptide (ANP), energy metabolism-related genes (EMRGs), serum testosterone (TT), SLCO1B1 rs4149056, fetuin-A, lipid-lowering drug targets, hyperhomocysteinemia (HHcy), and the molecular mechanism underlying the association between type 2 diabetes mellitus (T2DM) and atherosclerosis. The authors suggest that further research is needed to refine our understanding of CMD biomarkers and their diagnostic and prognostic value. [Extracted from the article]

This document is a letter published in the journal Intensive Care Medicine. The authors conducted a post-hoc analysis of the DOLPHIN trial, which compared standard antibiotic dosing to model-informed precision dosing in critically ill patients with an infection. The analysis focused on acute brain-injured (ABI) patients and their target attainment of beta-lactam antibiotics and ciprofloxacin. The results showed that ABI patients had a higher risk of failed target attainment compared to non-ABI patients, possibly due to augmented renal clearance. The authors suggest that further research should explore the potential benefit of higher antibiotic dosing in ABI patients. [Extracted from the article]

Introduction: The mechanisms underlying the protective effects of atrial natriuretic peptide (ANP) on the gut barrier during traumatic hemorrhagic shock (THS) remain elusive. This study aimed to explore the potential role of ANP in safeguarding against gut barrier dysfunction after THS, focusing on the PLC-γ1/ROS feedback loop. Methods: In our THS rat model, we randomly allocated male Sprague-Dawley rats to receive intravenous ANP with or without a concurrent NADPH oxidase/p38 MAPK inhibitor during the shock phase. After 24 h, we assessed circulatory and jejunal ANP, ROS, intestinal tight junction proteins, and apoptosis to evaluate the effects of ANP on the gut barrier and its interplay with intestinal ANP and ROS. Rat small intestinal epithelial cells (IECs) were also treated with ANP and subjected to hypoxia/re-oxygenation injury, with or without PI3K/PLC inhibition, to elucidate the relationship between ANP/ROS signaling and PLC-γ1. Furthermore, we modulated PLC-γ1 expression in these IECs to examine its impact on ROS and ANP production. Results: Intravenous ANP administration at 0.025 μg/kg/min during THS significantly increased intestinal ANP and ROS levels at 24 h. ANP treatment enhanced the expression of intestinal tight junction proteins and reduced IEC apoptosis. Inhibition of circulatory ROS diminished intestinal ANP levels, while suppression of circulatory ANP led to a reduction in intestinal ROS. Decreasing PLC-γ1 expression in hypoxia/re-oxygenation-treated IECs resulted in lower ROS and ANP levels, whereas augmenting PLC-γ1 expression did not alter these levels. Additionally, PI3K inhibition markedly decreased PLC-γ1 expression in these cells. Conclusion: ANP-induced protection of the intestinal barrier in THS is mediated by an intrinsic PLC-γ1/ROS positive feedback loop. ANP preserves gut barrier integrity and reduces IEC apoptosis through this mechanism. Further studies are warranted to investigate the interaction between IECs and other cellular components within the PLC-γ1/ROS loop. [ABSTRACT FROM AUTHOR]

Calorie restriction is a nutritional intervention that reproducibly protects against the maladaptive consequences of cardiovascular diseases. Pathological cardiac hypertrophy leads to cellular growth, dysfunction (with mitochondrial dysregulation), and oxidative stress. The mechanisms behind the cardiovascular protective effects of calorie restriction are still under investigation. In this study, we show that this dietetic intervention prevents cardiac protein elevation, avoids fetal gene reprogramming (atrial natriuretic peptide), and blocks the increase in heart weight per tibia length index (HW/TL) seen in isoproterenol-induced cardiac hypertrophy. Our findings suggest that calorie restriction inhibits cardiac pathological growth while also lowering mitochondrial reverse electron transport-induced hydrogen peroxide formation and improving mitochondrial content. Calorie restriction also attenuated the opening of the Ca2+-induced mitochondrial permeability transition pore. We also found that calorie restriction blocked the negative correlation of antioxidant enzymes (superoxide dimutase and glutatione peroxidase activity) and HW/TL, leading to the maintenance of protein sulphydryls and glutathione levels. Given the nature of isoproterenol-induced cardiac hypertrophy, we investigated whether calorie restriction could alter cardiac beta-adrenergic sensitivity. Using isolated rat hearts in a Langendorff system, we found that calorie restricted hearts have preserved beta-adrenergic signaling. In contrast, hypertrophic hearts (treated for seven days with isoproterenol) were insensitive to beta-adrenergic activation using isoproterenol (50 nM). Despite protecting against cardiac hypertrophy, calorie restriction did not alter the lack of responsiveness to isoproterenol in isolated hearts harvested from isoproterenol-treated rats. These results suggest (through a series of mitochondrial, oxidative stress, and cardiac hemodynamic studies) that calorie restriction possesses beneficial effects against hypertrophic cardiomyopathy. [ABSTRACT FROM AUTHOR]

BACKGROUND: Cardiac hypertrophy is an adaptive response of the heart to physiological and pathological stimuli such as pressure overload. It is of compensatory significance in the early stage, but if the stimulation continues, it can cause cardiomyopathy leading to heart failure. MicroRNAs are involved in the regulation of cardiac hypertrophy. However, the role of miR-20a in pressure overload-induced cardiac hypertrophy has not been reported. OBJECTIVE: To investigate the role of miR-20a in pressure overload-induced cardiac hypertrophy and the underlying mechanisms. METHODS: Transverse aortic constriction was used to induce cardiac hypertrophy in vivo and angiotensin II was used to induce H9c2 cell models of cardiac hypertrophy in vitro. MiR-20a was overexpressed in vivo by intramyocardial injection of miR-20a overexpressing adenovirus and in vitro by transfecting miR20a mimic into H9c2 cells. Cardiac hypertrophy was assessed by measuring heart weight/body weight ratio, cell surface area, and myocardial fibrosis. The expression levels of atrial natriuretic peptide, brain natriuretic peptide, β-myosin heavy chain and miR-20a were detected by real-time fluorescence quantitative PCR. Mitochondrial fission was detected by MitoTracker. The downstream target genes of miR-20a were predicted by RNAhybrid software. RESULTS AND CONCLUSION: (1) The expression level of miR-20a was significantly decreased in both hypertrophic cardiomyocytes and hearts (P < 0.05). (2) At the animal level, overexpression of miR-20a significantly inhibited transverse aortic constriction-induced cardiac hypertrophy, including decreasing the upregulated expression level of hypertrophic marker genes (P < 0.05), reduced the enlarged heart volume, reducing the increased heart weight/body weight ratio (P < 0.01), reducing the increased myocardial cross-sectional area (P < 0.05), and attenuating fibrosis (P < 0.01). (3) At the cellular level, overexpression of miR-20a significantly inhibited angiotensin II-induced cardiomyocyte hypertrophy, including decreasing the upregulated expression levels of atrial natriuretic peptide (P < 0.05), brain natriuretic peptide (P < 0.01) and β-myosin heavy chain (P < 0.05), reducing the increased protein/DNA ratio (P < 0.01), and suppressing the increased cell surface area (P < 0.05). (4) Overexpression of miR-20a significantly inhibited angiotensin II-induced mitochondrial fission (P < 0.05). (5) The results of RNAhybrid software analysis showed that miR-20a and the mRNA 3’ untranslated region of cAMP-dependent protein kinase inhibitor alpha were well complementary and the predicted binding sites were highly conserved. (6) In conclusion, miR-20a is significantly down-regulated in pressure overload-induced cardiac hypertrophy. Overexpression of miR-20a inhibits cardiac hypertrophy at both the cellular level and animal level and attenuates angiotensin II-induced mitochondrial fission. [ABSTRACT FROM AUTHOR]

Pierre Cornelis, a renowned microbiologist, passed away on December 2, 2023. He made significant contributions to the field of microbiology, particularly in the study of Pseudomonas bacteria and their iron uptake pathways. His research provided insights into siderophores and outer membrane transporters, shedding light on iron acquisition mechanisms and their role in microbial competition and pathogenicity. Cornelis also collaborated on projects related to porins and their regulation in Pseudomonas aeruginosa, biofilm formation, and the effects of host peptide hormones on the physiology of P. aeruginosa. He was highly respected in the scientific community and held leadership roles in scientific societies and editorial positions. Cornelis will be remembered not only for his academic achievements but also for his kindness, humility, and dedication to advancing scientific knowledge. [Extracted from the article]

Introduction: Chronic heart failure (CHF) is a leading cause of deaths induced by cardiovascular disease. This study aimed to investigate the protective effects of emodin in CHF rats and explore the related mechanisms. Material and methods: A total of 56 Wistar rats were used to construct CHF model using the coronary artery ligation. The effects of emodin on cardiac function and inflammation were analyzed in the CHF rats. Expression of miR-26b-5p in the CHF model before and after emodin treatment was estimated by quantitative real-time polymerase chain reaction. The effects of miR-26b-5p on cardiac function and inflammation were also assessed, and its target gene was predicted and confirmed in rat cardiomyocyte H9c2. Results: Emodin treatment could significant improve the cardiac function and inflammation evidenced by the increased increased ejection fraction (EF), fractional shortening (FS), left ventricular systolic pressure (LVSP) and maximum of the first differentiation of left ventricular pressure (+LV dP/dtmax) and decreased atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), left ventricular end diastolic pressure (LVEDP), interleukin (IL)-6, tumor necrosis factor α (TNF-α) levels. Expression of miR-26b-5p was downregulated in the CHF rats (CHF 0.442 ±0.131 vs. Sham 1.044 ±0.160), and this suppressive effect was rescued by emodin (Emodin 0.902 ±0.132 vs. CHF 0.442 ±0.131). The overexpression of miR-26b-5p in CHF rats led to improved cardiac function and inflammatory response. In addition, the emodin-induced increased EF, FS, LVSP and +LV dP/dtmax and decreased ANP, BNP, LVEDP, IL-6 and TNF-α were all abrogated by the knockdown of miR-26b-5p. The target prediction results revealed that PTEN was a target gene of miR-26b-5p in H9c2 cells. Conclusions: All the results indicated that emodin serves a protective role in CHF via regulation of the miR-26b-5p/PTEN pathway. Emodin may be an effective therapeutic agent for CHF treatment. [ABSTRACT FROM AUTHOR]

The global burden of cardiovascular diseases is indisputable, as it claims nearly 18 million lives a year. In this current study, we aimed to prove that exercise, a cornerstone in cardiovascular disease management, emerges as a powerful tool in the pathology of myocardial ischemia. Male rats were divided into three groups: pre-swimming training + isoproterenol (ISO) treated, isoproterenol-treated, and control-sedentary. Myocardial infarction was induced by the subcutaneous injection of 1.0 mg/kg ISO. After the subsequent rest period, the animals swam for 3 weeks, every day for 25 min. At the end of the experiment, the serum levels of atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP), as well as the cardiac concentrations of reactive oxygen species (ROS), catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD) were determined. Our results indicate that both cardiac injury biomarkers (ANP, BNP) and ROS levels were significantly lower in swimming rats compared to the sedentary animals. Moreover, the level of enzymatic components of the intracellular antioxidant system, CAT, SOD, and GPx were increased in swimming animals after ISO-induced myocardial infarction. Our findings support the fact that moderate-intensity swimming training can be efficiently used to prevent myocardial infarction-induced ischemic injury, by inhibiting ROS production and strengthening intracellular antioxidant defense. [ABSTRACT FROM AUTHOR]

Tri-Circulator (TC) is a product comprising coenzyme Q10 (CoQ10), Salvia miltiorrhiza, and Panax notoginseng. Individually, each of these constituents has demonstrated protective effects on myocardial injury. The purpose of this study is to evaluate the protective efficacy of TC on heart function and compare the differential effects between CoQ10 and TC. Two myocardial injury models of zebrafish, the hypoxia-reoxygenation model (H/R) and the isoproterenol (ISO, a β-receptor agonist) model, were used in this experiment. The zebrafish subjects were divided into 4 groups: control, H/R, TC, and CoQ10. Heart rate, stroke volume (SV), cardiac output (CO), ejection fraction (EF), fractional area change (FAC), and pericardial height were monitored to assess changes in heart function. The gene expression of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) was studied as markers of injury/stress. TC significantly suppresses elevated heart rate induced by H/R and prevents the decrease of heart rate induced by ISO. It alleviates the pericardial infusion induced by ISO, whereas CoQ10 does not possess a similar effect. Both TC and CoQ10 significantly inhibit the decline in SV, CO, EF, and FAC induced by H/R and ISO, and suppress the expression of ANP and BNP in cardiomyocytes induced by ISO. It is noteworthy that TC demonstrates a more pronounced effect on EF, FAC, ANP, and BNP gene expression compared to CoQ10. Both TC and CoQ10 have a protective effect on myocardial injury of zebrafish. However, TC exhibits a greater efficacy compared to CoQ10 alone in mitigating myocardial injury. [ABSTRACT FROM AUTHOR]

Bacground: Off-pump coronary artery bypass graft (OPCABG) has a high incidence of postoperative systemic inflammation response syndrome (SIRS), and perioperative endothelial glycocalyx layer (EGL) disruption can be one of the predisposing factors. We hypothesized that EGL shedding happened earlier in OPCABG which can influence on postoperative SIRS, and sevoflurane might preserve EGL better than propofol. Methods: We randomly allocated 50 patients undergoing OPCABG to receive either sevoflurane-sufentanil or propofol-sufentanil anesthesia. Plasma syndecan-1, heparan sulfate (HS), atrial natriuretic peptide (ANP), IL-6, and cardiac troponin I (cTnI) were measured. Blood samples were collected at 6 timepoints: induction (T1), before grafting (T2), after grafting(T3), surgery done (T4), postoperative day1 (POD1,T5) and POD2 (T6). SIRS criteria and sequential organ failure assessment (SOFA) score were examined. Results: There were neither differences of syndecan-1, HS, IL-6 nor of SIRS criteria or SOFA score between the sevoflurane and propofol groups. All patients were pooled as a single group for further statistical analyses, plasma syndecan-1 (P < 0.001) and IL-6 (P < 0.001) increased significantly as a function of time; syndecan-1 increasing correlated significantly with the duration of coronary graft anastomosis (r = 0.329, P = 0.026). Syndecan-1(T3) correlated significantly with ANP(T3) (r = 0.0.354, P = 0.016) and IL-6 (T5) (r = 0.570, P < 0.001). The maximum value of IL-6 correlated significantly with SIRS (r = 0.378, P = 0.010), the maximum value of SOFA score (r = 0.399, P = 0.006) and ICU days (r = 0.306, P = 0.039). The maximum value of SOFA score correlated significantly with the occurrence of SIRS (r = 0.568, P < 0.001) and ICU days (r = 0.338, P = 0.022). Conclusions: OPCABG intraoperative early EGL shedding caused of grafts anastomosis greatly affected postoperative SIRS and SOFA score, sevoflurane did not clinically preserve EGL better. Trial registration: ChiCTR-IOR-17012535. Registered on 01/09/2017. [ABSTRACT FROM AUTHOR]

Cardiac hypertrophy (CH) is an important characteristic in heart failure development. Chlorogenic acid (CGA), a crucial bioactive compound from honeysuckle, is reported to protect against CH. However, its underlying mechanism of action remains incompletely elucidated. Therefore, this study aimed to explore the mechanism underlying the protective effect of CGA on CH. This study established a CH model by stimulating AC16 cells with isoproterenol (Iso). The observed significant decrease in cell surface area, evaluated through fluorescence staining, along with the downregulation of CH-related markers, including atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and β-myosin heavy chain (β-MHC) at both mRNA and protein levels, provide compelling evidence of the protective effect of CGA against isoproterenol-induced CH. Mechanistically, CGA induced the expression of glycogen synthase kinase 3β (GSK-3β) while concurrently attenuating the expression of the core protein β-catenin in the Wnt/β-catenin signaling pathway. Furthermore, the experiment utilized the Wnt signaling activator IM-12 to observe its ability to modulate the impact of CGA pretreatment on the development of CH. Using the Gene Expression Omnibus (GEO) database combined with online platforms and tools, this study identified Wnt-related genes influenced by CGA in hypertrophic cardiomyopathy (HCM) and further validated the correlation between CGA and the Wnt/β-catenin signaling pathway in CH. This result provides new insights into the molecular mechanisms underlying the protective effect of CGA against CH, indicating CGA as a promising candidate for the prevention and treatment of heart diseases. [ABSTRACT FROM AUTHOR]

Regular waterpipe smoking (Reg-WPS) is well recognized for its deleterious effect on the heart. However, there is a paucity of experimental studies on the impact of occasional waterpipe smoking (Occ-WPS), also known as nondaily smoking, versus Reg-WPS on cardiac homeostasis, and the mechanisms underlying these effects. Hence, we aimed, in the present study, to investigate the effect of Occ-WPS (30 min/day, 1 day/week) versus Reg-WPS (30 min/day, 5 days/ week) for 6 months on systolic blood pressure (SBP), cardiac injury, oxidative markers, chemokines, proinflammatory cytokines, DNA damage and mitochondrial function compared with air (control) exposed mice. Our results show that SBP was increased following exposure to either Occ-WPS or Reg-WPS compared with air-exposed mice. Moreover, we found that only Reg-WPS induced a significant elevation in the levels of troponin I, brain natriuretic peptide, lactate dehydrogenase, and creatine phosphokinase. However, the atrial natriuretic peptide (ANP) was significantly increased in both Occ-WPS and Reg-WPS groups. Compared with air-exposed mice, the levels of lipid peroxidation, reduced glutathione and monocyte chemoattractant protein-1 were only significantly augmented in the Reg-WPS. However, catalase, superoxide dismutase, and CXCL1 were significantly increased in both OccWPS and Reg-WPS. The concentrations of the adhesion molecules E-selectin, vascular cell adhesion molecule-1, and intercellular adhesion molecule-1 were solely elevated in the heart of mice exposed to Reg-WPS. Similarly, the concentrations of interleukin-1β and tumor necrosis factor α were only significantly augmented in the Reg-WPS. However, both Occ-WPS and Reg-WPS triggered significant augmentation in the levels of IL17 and DNA damage compared to the control groups. Furthermore, while Occ-WPS induced a slight but statistically insignificant elevation in the concentrations of mammalian targets of rapamycin and nuclear factor erythroid-derived 2-like 2 (Nrf2) expression, Reg-WPS exposure increased their levels substantially, in addition to p53 and mitochondrial complexes II & III, and IV activities compared with air-exposed mice. In conclusion, our findings show that while the long-term Occ-WPS exposure induced an elevation of SBP, ANP, antioxidant enzymes, IL17, CXCL1, and cardiac DNA damage, Reg-WPS exposure was consistently associated with the elevation of SBP and occurrence of cardiac damage, inflammation, oxidative stress, DNA damage and mitochondrial dysfunction. [ABSTRACT FROM AUTHOR]

Introduction: Salusins, which are translated from the alternatively spliced mRNA of torsin family 2 member A (TOR2A), play a vital role in regulation of various cardiovascular diseases. However, it remains unclear precisely regarding their roles in hypertrophic cardiomyopathy (HCM). Therefore, this study was conducted to explore therapeutic effect and the underlying mechanisms of salusins on HCM. Material and methods: In vivo experiments, Sprague–Dawley rats were used to induce HCM model by angiotensin (Ang) II infusion for 4 weeks. The rats were randomly divided into four groups, namely, Saline + Control shRNA (n = 7), Ang II + Control shRNA (n = 8), Saline + TOR2A shRNA (n = 7), and Ang II + TOR2A shRNA groups (n = 8). After HCM induction, doppler echocardiography is recommended to evaluate heart function. In vitro experiments, primary neonatal rat cardiomyocytes (NRCMs) and cardiac fibroblasts (NRCFs) were obtained from newborn rats, and were treated with Ang II (10–6 M) for 24 h. Results: After treatment with Ang II, levels of salusin-α and salusin-β were elevated in serum and cardiac tissues of rats and in the neonatal rat cardiomyocytes and cardiac fibroblasts. Downregulation of salusins alleviated the Ang II-induced cardiac hypertrophy by suppressing the increased atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and beta-myosin heavy chain (β-MHC) and cardiac fibrosis by blocking collagen I, collagen III and transforming growth factor-beta (TGF-β), and it also attenuated oxidative stress by suppressing the increased reactive oxygen species (ROS) and malondialdehyde (MDA) levels and reversing the decreased superoxide dismutase (SOD) activity and autophagy by inhibiting the increased microtubule-associated protein light chain 3B (LC3B), Beclin1, autophagy related gene (Atg) 3 and Atg5 in the cardiac tissues of Ang II-infused rats and in the Ang II-treated NRCMs. Conclusions: All these findings suggest that the levels of salusins were elevated in the HCM, and targeting of salusins contributes to alleviation of cardiac hypertrophy and fibrosis probably via attenuating oxidative stress and autophagy. Accordingly, targeting of salusins may be a strategy for HCM therapy. [ABSTRACT FROM AUTHOR]

This article discusses the relationship between traumatic brain injury (TBI) and kidney dysfunction. TBI can lead to increased renal clearance, which can affect drug dosing strategies and renal function. The mechanisms involved in kidney damage after TBI are not fully understood, but they may be related to the systemic inflammatory response and hemodynamic alterations. Patients with TBI are at a higher risk of developing augmented renal clearance (ARC), which can lead to subtherapeutic drug levels and treatment failure. Acute kidney injury (AKI) is also a common occurrence after TBI and can worsen patient outcomes. Modifiable factors that contribute to AKI include osmotic therapy, exposure to nephrotoxic agents, and sodium management. The optimal strategy for preventing and treating AKI in TBI patients remains uncertain, but guidelines recommend avoiding nephrotoxic agents and optimizing fluid status and hemodynamics. Continuous kidney replacement therapy may be necessary for patients with progressive AKI. Future research should focus on diagnostic approaches and biomarkers for kidney damage in TBI patients. [Extracted from the article]

Objective: The aim of this study was to investigate the role of the follistatin‐like 1 (Fstl1) and disco‐interacting protein 2 homolog A (DIP2a) axis in relation to lipid metabolism during and after endurance exercise and to elucidate the mechanisms underlying the metabolic effects of Fstl1 on adipocytes, considering its regulation by exercise and muscle mass and its link to obesity. Methods: Twenty‐nine sedentary males participated in endurance exercise, and blood samples were collected during and after the exercise. Body composition, Fstl1, glycerol, epinephrine, growth hormone, and atrial natriuretic peptide were measured. 3T3‐L1 adipocytes, with or without DIP2a knockdown, were treated with Fstl1 to assess glycerol release, cyclic AMP/cyclic GMP production, and hormone sensitive lipase phosphorylation. The association between DIP2a gene expression levels in human adipose tissues and exercise‐induced lipolysis was examined. Results: Fstl1 levels significantly increased during endurance exercise and following recovery, correlating with lean body mass and lipolysis. In 3T3‐L1 adipocytes, Fstl1 increased glycerol release, cyclic GMP production, and hormone sensitive lipase activation, but these effects were attenuated by DIP2a knockdown. DIP2a gene expression in human adipose tissues correlated with serum glycerol concentrations during endurance exercise. Conclusions: Fstl1 is a myokine facilitating lipid mobilization during and after endurance exercise through DIP2a‐mediated lipolytic effects in adipocytes. [ABSTRACT FROM AUTHOR]

Cardiac hypertrophy (CH) is an early marker in the clinical course of heart failure. Circular RNAs (circRNAs) play important roles in human disease. However, the role of circ_Larp4b in myocardial hypertrophy has not been studied. Angiotensin II (Ang II) treated HL-1 cells to induce a CH cell model. Quantitative real-time polymerase chain reaction was used to detect the expression of circ_Larp4b, microRNA-298-5p, and myocyte enhancer factor 2 (Mef2c). Western blot detected the protein level of alpha-actinin-2 (ACTN2), beta-myosin heavy chain (β-MHC), atrial natriuretic peptide (ANP), and Mef2c. The relationship between miR-298-5p and circ_Larp4b or Mef2c was verified by dual-luciferase reporter assay and RNA pull-down assay. Circ_Larp4b and Mef2c were upregulated in HL-1 cells treated with Ang II. Moreover, circ_Larp4b down-regulation regulated the progress of CH induced by Ang II. MiR-298-5p was a target of circ_Larp4b, and Mef2c was a target of miR-298-5p. Overexpressed Mef2c reversed the cell size inhibited by miR-298-5p in Ang II-induced HL-1 cells. Circ_Larp4b regulated CH progress by regulating miR-298-5p/Mef2c axis. [ABSTRACT FROM AUTHOR]

Flaxseed is an ancient commercial oil that historically has been used as a functional food to lower cholesterol levels. However, despite its longstanding treatment, there is currently a lack of scientific evidence to support its role in the management of cardiac remodeling. This study aimed to address this gap in knowledge by examining the molecular mechanism of standardized flaxseed oil in restoring cardiac remodeling in the heart toxicity vivo model. The oil fraction was purified, and the major components were standardized by qualitative and quantitative analysis. In vivo experimental design was conducted using isoproterenol ISO (85 mg/kg) twice subcutaneously within 24 h between each dose. The rats were treated with flaxseed oil fraction (100 mg/kg orally) and the same dose was used for omega 3 supplement as a positive control group. The GC-MS analysis revealed that α-linolenic acid (24.6%), oleic acid (10.5%), glycerol oleate (9.0%) and 2,3-dihydroxypropyl elaidate (7%) are the major components of oil fraction. Physicochemical analysis indicated that the acidity percentage, saponification, peroxide, and iodine values were 0.43, 188.57, 1.22, and 122.34 respectively. As compared with healthy control, ISO group-induced changes in functional cardiac parameters. After 28-day pretreatment with flaxseed oil, the results indicated an improvement in cardiac function, a decrease in apoptosis, and simultaneous prevention of myocardial fibrosis. The plasma levels of BNP, NT-pro-BNP, endothelin-1, Lp-PLA2, and MMP2, and cTnI and cTn were significantly diminished, while a higher plasma level of Topo 2B was observed. Additionally, miRNA − 1 and 29b were significantly downregulated. These findings provide novel insight into the mechanism of flaxseed oil in restoring cardiac remodeling and support its future application as a cardioprotective against heart diseases. [ABSTRACT FROM AUTHOR]

Objective: This study investigated remodeling of cellular metabolism and structures during browning of primary human adipocytes derived from both visceral and subcutaneous adipose tissues. Effects of glucocorticoids on the browning were also assessed. Methods: Differentiated omental and subcutaneous human adipocytes were treated with rosiglitazone, with or without dexamethasone, and expression levels of brite adipocyte markers, lipolysis, and lipid droplet and mitochondrial structures were examined. Results: Both omental and subcutaneous adipocytes acquired brite phenotypes upon peroxisome proliferator‐activated receptor‐γ agonist treatment, and dexamethasone tended to enhance the remodeling. Although rosiglitazone increased lipolysis during treatment, brite adipocytes exhibited lower basal lipolytic rates and enhanced responses to β‐adrenergic agonists or atrial natriuretic peptide. Transcriptome analysis identified induction of both breakdown and biosynthesis of lipids in brite adipocytes. After 60+ days in culture, lipid droplet size increased to ~50 microns, becoming almost unilocular in control adipocytes, and after browning, they acquired paucilocular morphology, clusters of small lipid droplets (1–2 micron) surrounded by mitochondria appearing on the periphery of the central large one. Conclusions: Metabolic and structural remodeling during browning of primary human adipocytes is similar to previous findings in human adipocytes in vivo, supporting their uses for mechanical studies investigating browning with translational relevance. [ABSTRACT FROM AUTHOR]

The article discusses the use of B-type natriuretic peptide (BNP) as a biomarker in adult congenital heart disease (ACHD). The study analyzed a cohort of 3,392 ACHD patients and found that higher levels of BNP were associated with increased mortality. However, the relationship between BNP and mortality varied among different ACHD diagnoses. The findings highlight the need for further research and the development of diagnosis-specific metrics to accurately assess the prognostic performance of BNP in ACHD patients. International collaboration and large prospective registries are necessary to establish the roles of biomarkers and risk scores in individual ACHD diagnoses. [Extracted from the article]

This article discusses the cardiac risks associated with long-distance running. It begins by recounting the story of Pheidippides, the messenger who inspired the modern marathon race but died upon completing his run. The cause of his death is unknown but may have been related to prolonged strenuous exercise. The article then explores the beneficial effects of regular exercise on cardiovascular health, as well as the potential risks of excessive endurance exercise. It emphasizes the importance of screening individuals before participating in marathons to prevent sudden cardiac death and identifies limitations in current screening criteria. The article concludes by highlighting the need for individuals to be fully informed about the potential long-term adverse effects of repetitive long-distance running and suggests the use of national and international registries to identify those at risk for adverse cardiovascular events. [Extracted from the article]

Background and Purpose: Guanylyl cyclase-A (GC-A), activated by endogenous atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), plays an important role in the regulation of cardiovascular and renal homeostasis and is an attractive drug target. Even though small molecule modulators allow oral administration and longer half-life, drug targeting of GC-A has so far been limited to peptides. Thus, in this study we aimed to develop small molecular activators of GC-A. Experimental Approach: Hits were identified through high-throughput screening and optimized by in silico design. Cyclic GMP was measured in QBIHEK293A cells expressing GC-A, GC-B or chimerae of the two receptors using AlphaScreen technology. Binding assays were performed in membrane preparations or whole cells using 125I-ANP. Vasorelaxation was measured in aortic rings isolated from Wistar rats. Key Results: We have identified small molecular allosteric enhancers of GC-A, which enhanced ANP or BNP effects in cellular systems and ANP-induced vasorelaxation in rat aortic rings. The mechanism of action appears novel and not mediated through previously described allosteric binding sites. In addition, the selectivity and activity depend on a single amino acid residue that differs between the two similar receptors GC-A and GC-B. Conclusion and Implications: We describe a novel allosteric binding site on GC-A, which can be targeted by small molecules to enhance ANP and BNP effects. These compounds will be valuable tools in further development and proof-of-concept of GC-A enhancement for the potential use in cardiovascular therapy. [ABSTRACT FROM AUTHOR]

Hydrogen sulfide (H2S), the third gasotransmitter, plays a critical role in protecting against heart failure. Sirtuin-1 (SIRT1) is a highly conserved histone deacetylase that has a protective role in the treatment of heart failure by regulating the deacetylation of some functional proteins. This study investigates the interaction between SIRT1 and H2S in heart failure and the underlying mechanisms. Using endogenous H2S-generating enzyme cystathionine γ-lyase (CSE) knockout mice, we found that CSE deficiency aggravated isoprenaline-induced cardiac injury. Treatment with H2S attenuated atrial natriuretic peptide level, brain natriuretic peptide level, improved cardiac function. Moreover, H2S treatment potentiated myocardial SIRT1 expression. Silencing CSE abolished intracellular SIRT1 expression. Furthermore, CSE/ H2S S-sulfhydrated SIRT1 at its zinc finger domains and augmented its zinc ion binding activity to stabilize the alpha-helix structure. In conclusion, these results uncover that a novel mechanism that CSE/H2S S-sulfhydrated SIRT1 to prevent heart dysfunction through modulating its activity. [ABSTRACT FROM AUTHOR]

Dyxin is a LIM-domain containing transcriptional regulator protein shown to play a role in a hypertrophic response in the heart. Here, the effect of adenoviral dyxin overexpression was studied on cardiac function and gene expression in the normal heart and in angiotensin II (Ang II)-induced hypertension in rats. The adenovirus-mediated intramyocardial gene transfer of dyxin (1.5×109 infectious units/animal) was performed into the left ventricle (LV) of Sprague-Dawley rats with and without the Ang II (33 µg/kg/h) infusion, administered via osmotic minipumps for 1 and 2 weeks. Echocardiography was used to assess the structural and functional changes. Dyxin expression and localization in the heart was analyzed with quantitative RT-PCR and immunohistochemistry, respectively. In the normal rat heart, the adenoviral overexpression of dyxin did not alter LV function in normal hearts as assessed by echocardiography. Dyxin was found to be localized in the cardiomyocytes as shown by the immunohistochemical staining. In Ang II-induced hypertrophy, echocardiographic data revealed a significant increase in the posterior wall diameter both in systole (21%, P<0.05) and diastole (21%, P<0.01) as well as in the diameter of the interventricular septum in systole (19%, P<0.05) in the dyxin-injected group compared with the LacZ-injected animals after two weeks of Ang II infusion. Interestingly, a significant decrease in the levels of both atrial natriuretic peptide (ANP) mRNA (55%, P<0.01) and B-type natriuretic peptide (BNP) mRNA (68%, P<0.05) was observed in the dyxin-injected group compared with the LacZ control group after one week of Ang II infusion. These results indicate that dyxin overexpression was deteriorative against pressure overload by inducing structural changes in the LV in rats. Interestingly, simultaneous adenoviral overexpression of dyxin suppressed the Ang II-induced changes of ANP and BNP genes suggesting that dyxin might have a role as a regulator of the cardiac hypertrophic gene program. [ABSTRACT FROM AUTHOR]

It has been established that the human atrial natriuretic peptide is able to alter the effect of azithromycin on Kytococcus schroeteri H01 and Staphylococcus aureus 209P monospecies and binary biofilms. The effect of the hormone depends on the surface type and cultivation system, and it may have both enhancing and counteracting effects. The antagonistic effect of the hormone was observed mostly on hydrophobic surfaces, whereas the additive effect was observed on hydrophilic surfaces like glass. Also, the effect of the hormone depends on the antibiotic concentration and bacterial species. The combination of azithromycin and ANP led to an amplification of cell aggregation in biofilms, to the potential increase in matrix synthesis, and to a decrease in S. aureus in the binary community. Also, ANP, azithromycin, and their combinations caused the differential expression of genes of resistance to different antibiotics, like macrolides (mostly increasing expression in kytococci), fluoroquinolones, aminoglycosides, and others, in both bacteria. [ABSTRACT FROM AUTHOR]

Atrial natriuretic peptide (ANP) is a peptide hormone that regulates blood pressure and volume. ANP interacts with natriuretic peptide receptor-A (NPR-A) to lower the blood pressure through vasodilation, diuresis and natriuresis. Previously, we designed two human ANP analogues, one with exclusively diuretic function (DGD-ANP) and the other with exclusively vasodilatory function (DRD-ANP). Although both ANP analogues interact with NPR-A, their ability to produce cGMP was different. Three alternatively spliced isoforms of NPR-A were previously identified in rodents. Here, we evaluated the putative human isoforms for their cGMP production independently and in combination with WT NPR-A in various percentages. All three NPR-A isoforms failed to produce cGMP in the presence of ANP, DGD-ANP, or DRD-ANP. Co-expression of isoforms with WT NPR-A were found to significantly impair cGMP production. Considering the differential tissue expression levels of all three spliced isoforms in rodents have previously been demonstrated, the existence of these non-functional receptor isoforms may act as negative regulator for ANP/NPR-A activation and fine-tune cGMP production by WT NPR-A to different degree in different tissues. Thus, NPR-A isoforms potentially contribute to tissue-specific functions of ANP. [ABSTRACT FROM AUTHOR]

Intradialytic hypotension and arrhythmias are complications of hemodialysis. They are associated with decreased intravascular volume due to reduced ultrafiltration volume, cardiac function, and arterial tone. The vascular endothelial glycocalyx, which exists on the surface of healthy vascular endothelial cells and maintains vascular permeability, has been suggested to be impaired by hemodialysis. This single-center retrospective study evaluated the association between syndecan-1, an endothelial glycocalyx dysfunction marker, and complications of hemodialysis. We enrolled 92 patients who underwent outpatient hemodialysis at Gifu Seiryu Hospital from April to July 2022 (346 hemodialysis sessions). The median duration and time of hemodialysis were 40 months and 4.1 h, respectively. Median serum syndecan-1 levels were 67.7 ng/mL before and 98.3 ng/mL after hemodialysis. Hemodialysis complications were noted in 68 sessions, all of which were hypotension. No correlation between pre-hemodialysis syndecan-1 levels and the incidence of complications was observed. However, a positive correlation between the amount of change in syndecan-1 levels before and after hemodialysis and the incidence of hemodialysis complications was noted. Conversely, syndecan-1 levels did not correlate with brain or atrial natriuretic peptides, suggesting that impairment of the vascular endothelial glycocalyx may be a possible cause of intradialytic hypotension and may be useful in preventing intradialytic hypotension. [ABSTRACT FROM AUTHOR]