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Annexin A5 (ANXA5) is a small calcium-dependent protein that binds specifically to negatively charged phosphatidylserine as a marker of apoptosis. Previous studies have shown that ANXA5 expression is elevated in hypertensive patients and is closely related to left ventricular systolic function in hypertensive patients, but its specific mechanism of action has not been clarified. GEO database analysis showed that ANXA5 expression was significantly upregulated in hypertensive myocardial hypertrophy. The expression of ANXA5 protein and mRNA was overexpressed, and knockdown of ANXA5 can effectively attenuate cardiomyocyte apoptosis and inflammatory response, ameliorate myocardial hypertrophy and cardiac dysfunction in ALD-induced hypertrophic cardiomyocytes and in SHR hypertrophic hearts. Mechanistically, ANXA5 has synergistic effect with intracellular calciumion level. In the meantime, ANXA5 knockdown inhibited cell apoptosis along with a decrease of Bax/Bcl-2 ratio, and induction of PI3K/AKT activation. It should be noted that LY290004 (PI3K/Akt signaling pathway inhibitor) can weaken the inhibitory effect of knockdown ANXA5 on cardiomyocyte apoptosis and myocardial protection. Therefore, ANXA5 knockdown improves hypertensive myocardial hypertrophy and cardiac function by inhibiting apoptosis and inflammatory response and activating PI3K/AKT/Bcl-2 pathway, ANXA5 may be a potential therapeutic direction for the treatment of hypertensive myocardial hypertrophy. [ABSTRACT FROM AUTHOR]

Aim. To determine the incidence of interstitial myocardial fibrosis (MF) in acromegaly, which leads to the development of cardiac arrhythmias and conduction disorders. Materials and methods. A single-center study was conducted, including 70 patients with acromegaly. All patients underwent standard medical examinations, including hormonal blood tests, electrocardiograms, echocardiography, Holter monitoring electrocardiograms and magnetic resonance imaging (MRI) of the heart with gadolinium contrast, additionally 48 patients underwent T1-mapping, which is an MRI method that allows the detection of diffuse changes by measuring the values of myocardial relaxation time – T1. Results. The study revealed a high incidence of MF – 53 (75.7%) cases (21 women, 32 men). The duration of the disease was found to be critical for myocardial remodeling (p=0.006). Compliance criteria for the T1-mapping technique were determined, with reduced T1-mapping values observed in 85.2% of cases. The ROC analysis (Receiver Operator Characteristic) determined the diagnostic value of post-contrast T1-mapping: AUC (Area Under the Curve)=0.906 (95% confidence interval 0.789–1.000), a sensitivity of 90%, and a specificity of 76.5%, indicating high diagnostic efficiency. According to the Youden index, a cut-off point of 372.5 ms was selected. Conclusion. Myocardial T1-mapping is a novel MRI method that allows to assess the degree of MF without the need for myocardial biopsy. The obtained information is crucial for the diagnosis and prognostic assessment of heart diseases, particularly in cases of hypertrophic cardiomyopathy or infiltrative diseases. The T1-mapping method, which is actively developing, can serve as a marker for early diffuse myocardial fibrosis and help determine the prognosis for patients with acromegalic cardiomyopathy.

Background: Investigating the effect of sex on pressure unloading therapy in a clinical scenario is limited by several non-standardized factors. Hence, we sought to study sex-related similarities and differences under laboratory conditions. Methods: Pressure overload was induced in male and female rats by aortic banding (AB) for 6 and 12 weeks. Age-matched sham operated animals served as controls. Pressure unloading was performed by aortic debanding at week 6. Different aspects of myocardial remodeling were characterized by echocardiography, pressure-volume analysis, histology, qRT-PCR and explorative proteomics. Results: Hypertrophy, increased fetal gene expression, interstitial fibrosis, and prolonged active relaxation were noted in the AB groups at week 6 in both sexes. However, decompensation of systolic function and further deterioration of diastolic function only occurred in male AB rats at week 12. AB induced similar proteomic alterations in both sexes at week 6, while characteristic differences were found at week 12. After debanding, regression of hypertrophy and recovery of diastolic function took place to a similar extent in both sexes. Nevertheless, fibrosis, transcription of β-to-α myosin-heavy chain ratio, and myocardial proteomic alterations were reduced to a greater degree in females compared to males. Pressure unloading exposes a more pronounced anti-remodeling effect on the functional level in males, which is attributed to the more progressive functional deterioration in AB animals. Conclusions: Pressure unloading exposes reverse and anti-remodeling properties in both sexes. Female sex is associated with greater reversibility of fibrosis, fetal gene expression, and proteomic alterations. Nevertheless, pressure unloading exposes a more pronounced anti-remodeling effect on the functional level in males.

Aim. To describe a clinical case of transthyretin amyloidosis, the first manifestation of which was an episode of acute heart failure.Materials and methods. Patient V., 58 years old, was taken to the intensive care unit for patients with myocardial infarction V.P. Demikhov State Clinical Hospital with a preliminary diagnosis: acute coronary syndrome without ST segment elevation, pulmonary edema. It is known from the anamnesis that the patient was disturbed for 3 months by a pronounced dry cough, hoarseness of voice, weakness with minor physical exertion.Results. The complexity of the diagnosis of postmortem diagnosis of systemic amyloidosis was explained by the absence of any clinical manifestations that made it possible to suspect a deadly disease before hospitalization for pulmonary edema. This clinical case demonstrates the rapid development of symptoms of systemic amyloidosis. From the moment of the first symptoms (persistent dry cough, hoarseness of voice) to death as a result of heart failure, about 3 months have passed. The addition of peripheral polyneuropathy to the clinical picture made it possible to suspect a systemic disease.Conclusion. This clinical case proves the relevance and importance of timely diagnosis of amyloidosis, as well as the need to raise awareness of doctors of various specialties about this disease.

Yu-Qing Tan,1,* Wang Zhang,2,* Zi-Cong Xie,1 Jun Li,1 Heng-Wen Chen3 1Department of Cardiology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, People’s Republic of China; 2Department of Pharmacy, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, People’s Republic of China; 3New Drug Research and Development Office, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jun Li; Heng-Wen Chen, Email 13051458913@163.com; chenhengwen@163.comAbstract: Cardiovascular diseases (CVDs) tend to affect the young population and are associated with a significant economic burden and psychological distress to the society and families. The physiological and pathological processes underlying CVDs are complex. Ca2+/calmodulin-dependent kinase II (CaMK II), a protein kinase, has multiple biological functions. It participates in multiple pathological processes and plays a central role in the development of CVDs. Based on this, this paper analyzes the structural characteristics and distribution of CaMK II, the mechanism of action of CaMK II, and the relationship between CaMK II and CVDs, including ion channels, ischemia-reperfusion injury, arrhythmias, myocardial hypertrophy, cardiotoxicity, hypertension, and dilated cardiomyopathy. Given the different regulatory mechanisms of different isoforms of CaMK II, the clinical use of specific targeted inhibitors or novel compounds should be evaluated in future research to provide new directions.Keywords: CaMK II, cardiovascular diseases, ischemia-reperfusion injury, arrhythmias, myocardial hypertrophy

Na Yan,1 Xianggui Wang,1 Zufang Xu,1 Linling Zhong,1 Jiangyong Yang2 1Department of Vasculocardiology, Ganzhou People’s Hospital, Ganzhou, People’s Republic of China; 2Department of Cardiology, Ganzhou Hospital of Guangdong Provincial People’s Hospital, Ganzhou Municipal Hospital, Ganzhou, People’s Republic of ChinaCorrespondence: Jiangyong Yang, Department of Cardiology, Ganzhou Hospital of Guangdong Provincial People’s Hospital, Ganzhou Municipal Hospital, No. 49, Dagong Road, Ganzhou, 341000, People’s Republic of China, Tel +86-797-8208553, Email yangjy19861208@163.comIntroduction: Apigenin is a natural flavonoid compound with promising potential for the attenuation of myocardial hypertrophy (MH). The compound can also modulate the expression of miR-185-5p that both promote MH and suppress autophagy. The current attempts to explain the anti-MH effect of apigenin by focusing on changes in miR-185-5p-mediated autophagy.Methods: Hypertrophic symptoms were induced in rats using transverse aortic constriction (TAC) method and in cardiomyocytes using Ang II and then handled with apigenin. Changes in myocardial function and structure and cell viability and surface area were measured. The role of miR-185-5p in the anti-MH function of apigenin was explored by detecting changes in autophagic processes and miR-185-5p/SREBP2 axis.Results: TAC surgery induced weight increase, structure destruction, and collagen deposition in hearts of model rats. Ang II suppresses cardiomyocyte viability and increased cell surface area. All these impairments were attenuated by apigenin and were associated with the restored level of autophagy. At the molecular level, the expression of miR-185-5p was up-regulated by TAC, while the expression of SREBP2 was down-regulated, which was reserved by apigenin both in vivo and in vitro. The induction of miR-185-5p in cardiomyocytes could counteracted the protective effects of apigenin.Discussion: Collectively, the findings outlined in the current study highlighted that apigenin showed anti-MH effects. The effects were related to the inhibition of miR-185-5p and activation of SREBP, which contributed to the increased autophagy.Keywords: apigenin, autophagy, miR-185-5p, myocardial hypertrophy, SREBP2

Sialylation catalysed by sialyltransferase 7A (SIAT7A) plays a role in the development of cardiac hypertrophy. However, the regulatory mechanisms upstream of SIAT7A in this context remain poorly elucidated. Previous study demonstrated that KLF4 activates the SIAT7A gene in ischemic myocardium by binding to its promoter region. Nevertheless, the potential involvement of KLF4 in regulating SIAT7A expression in Ang II‐induced hypertrophic cardiomyocytes remains uncertain. This study seeks to deepen the underlying mechanisms of the KLF4 and SIAT7A interaction in the progression of Ang II‐induced cardiac hypertrophy. The results showed a concurrent increase in SIAT7A and KLF4 levels in hypertrophic myocardium of essential hypertension patients and in hypertrophic cardiomyocytes stimulated by Ang II. In vitro experiments revealed that reducing KLF4 levels led to a decrease in both SIAT7A synthesis and Sialyl‐Tn antigen expression, consequently inhibiting Ang II‐induced cardiomyocyte hypertrophy. Intriguingly, reducing SIAT7A levels also resulted in decreased KLF4 expression and suppression cardiomyocyte hypertrophy. Consistent with this, elevating SIAT7A levels increased KLF4 expression and exacerbated cardiomyocyte hypertrophy in both in vivo and in vitro experiments. Additionally, a time‐course analysis indicated that KLF4 expression preceded that of SIAT7A. Luciferase reporter assays further confirmed that modulating SIAT7A levels directly influenced the transcriptional activity of KLF4 in cardiomyocytes. In summary, KLF4 expression is upregulated in cardiomyocytes treated with Ang II, which subsequently induces the expression of SIAT7A. The elevated levels of SIAT7A, in turn, enhance the transcription of KLF4. These findings suggest a positive feedback loop between KLF4 and SIAT7A‐Sialyl‐Tn, ultimately promoting Ang II‐induced cardiac hypertrophy. [ABSTRACT FROM AUTHOR]

AbstractCelastrol (CEL) belongs to the group of non-steroidal immunosuppressants with the potential to improve cardiac hypertrophy (CH). However, the poor biocompatibility and low bioavailability of CEL limit its in vivo application. This study was aimed to develop a targeted drug delivery system that can efficiently and safely deliver CEL to target tissues, providing a research basis for the application of CEL in CH therapy. A novel ROS-sensitive drug-loaded nanomicelle, dodecanoic acid (DA)-phenylboronic acid pinacol ester-dextran polymer encapsulating CEL (DBD@CEL), was synthesized using chemical synthesis. Then, the morphology, particle size, drug-loaded content, and ROS-responsive release behavior of DBD@CEL were studied. Pharmacokinetics and biocompatibility were evaluated using healthy mice. Finally, the ability and mechanism of DBD@CEL in improving CH in vivo were investigated using a mouse CH model. DBD@CEL was successfully prepared with a drug loading of 18.9%. It exhibited excellent stability with an average particle size of 110.0 ± 1.7 nm. Within 48 h, DBD@CEL released only 19.4% in the absence of H2O2, while in the presence of 1 mM H2O2, the release rate increased to 71.5%. Biocompatibility studies indicated that DBD@CEL did not cause blood cell hemolysis, had no impact on normal organs, and did not result in abnormal blood biochemical indicators, demonstrating excellent biocompatibility. In vivo studies revealed that DBD@CEL regulated the activation of NF-κB signaling, inhibits pyroptosis and oxidative stress, and thereby ameliorates CH. The ROS-responsive DBD@CEL nanodrug delivery system enhances the therapeutic activity of CEL for CH, providing a promising drug delivery system for the clinical treatment of CH. [ABSTRACT FROM AUTHOR]

Renovascular hypertension (RH), a secondary hypertension, can significantly impact heart health, resulting in heart damage and dysfunction, thereby elevating the risk of cardiovascular diseases. Coniferol (CA), which has vascular relaxation properties, is expected to be able to treat hypertension-related diseases. However, its potential effects on cardiac function after RH remain unclear. In this study, in combination with network pharmacology, the antihypertensive and cardioprotective effects of CA in a two-kidney, one-clip (2K1C) mice model and its ability to mitigate angiotensin II (Ang II)-induced hypertrophy in H9C2 cells were investigated. The findings revealed that CA effectively reduced blood pressure, myocardial tissue damage, and inflammation after RH. The possible targets of CA for RH treatment were screened by network pharmacology. The interleukin-17 (IL-17) and tumor necrosis factor (TNF) signaling pathways were identified using a Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The inflammatory response was identified using a Gene Ontology (GO) enrichment analysis. Western blot analysis confirmed that CA reduced the expression of IL-17, matrix metallopeptidase 9 (MMP9), cyclooxygenase 2 (COX2), and TNF α in heart tissues and the H9C2 cells. In summary, CA inhibited cardiac inflammation and fibrohypertrophy following RH. This effect was closely linked to the expression of MMP9/COX2/TNF α/IL-17. This study sheds light on the therapeutic potential of CA for treating RH-induced myocardial hypertrophy and provides insights into its underlying mechanisms, positioning CA as a promising candidate for future drug development. [ABSTRACT FROM AUTHOR]

Li, Xiaoxu, Zhijun Pu, Gang Xu, Yidong Yang, Yu Cui, Xiaoying Zhou, Chenyuan Wang, Zhifeng Zhong, Simin Zhou, Jun Yin, Fabo Shan, Chengzhong Yang, Li Jiao, Dewei Chen, and Jian Huang. Hypoxia-induced myocardial hypertrophy companies with apoptosis enhancement and p38-MAPK pathway activation. High Alt Med Biol. 25:186–196, 2024. Background: Right ventricular function and remodeling are closely associated with symptom severity and patient survival in hypoxic pulmonary hypertension. However, the detailed molecular mechanisms underlying hypoxia-induced myocardial hypertrophy remain unclear. Methods: In Sprague–Dawley rats, hemodynamics were assessed under both normoxia and hypobaric hypoxia at intervals of 7 (H7), 14 (H14), and 28 (H28) days. Morphological changes in myocardial tissue were examined using hematoxylin and eosin (HE) staining, while myocardial hypertrophy was evaluated with wheat germ agglutinin (WGA) staining. Apoptosis was determined through TUNEL assays. To further understand the mechanism of myocardial hypertrophy, RNA sequencing was conducted, with findings validated via Western blot analysis. Results: The study demonstrated increased hypoxic pulmonary hypertension and improved right ventricular diastolic and systolic function in the rat models. Significant elevations in pulmonary arterial systolic pressure (PASP), mean pulmonary arterial pressure (mPAP), right ventricular mean pressure (RVMP), and the absolute value of +dp/dtmax were observed in the H14 and H28 groups compared with controls. In addition, right ventricular systolic pressure (RVSP), −dp/dtmax, and the mean dp/dt during isovolumetric relaxation period were notably higher in the H28 group. Heart rate increased in the H14 group, whereas the time constant of right ventricular isovolumic relaxation (tau) was reduced in both H14 and H28 groups. Both the right heart hypertrophy index and the heart weight/body weight ratio (HW/BW) were elevated in the H14 and H28 groups. Myocardial cell cross-sectional area also increased, as shown by HE and WGA staining. Western blot results revealed upregulated HIF-1α levels and enhanced HIF-2α expression in the H7 group. In addition, phosphorylation of p38 and c-fos was augmented in the H28 group. The H28 group showed elevated levels of Cytochrome C (Cyto C), whereas the H14 and H28 groups exhibited increased levels of Cleaved Caspase-3 and the Bax/Bcl-2 ratio. TUNEL analysis revealed a rise in apoptosis with the extension of hypoxia duration in the right ventricle. Conclusions: The study established a link between apoptosis and p38-MAPK pathway activation in hypoxia-induced myocardial hypertrophy, suggesting their significant roles in this pathological process. [ABSTRACT FROM AUTHOR]

Background: In humans, ACTN2 mutations are identified as highly relevant to a range of cardiomyopathies such as DCM and HCM, while their association with sudden cardiac death has been observed in forensic cases. Although ACTN2 has been shown to regulate sarcomere Z-disc organization, a causal relationship between ACTN2 dysregulation and cardiomyopathies under chronic stress has not yet been investigated. Objective: In this work, we explored the relationship between Actn2 dysregulation and cardiomyopathies under dexamethasone treatment. Methods: Previous cases of ACTN2 mutations were collected and the conservative analysis was carried out by MEGA 11, the possible impact on the stability and function of ACTN2 affected by these mutations was predicted by Polyphen-2. ACTN2 was suppressed by siRNA in H9c2 cells under dexamethasone treatment to mimic the chronic stress in vitro. Then the cardiac hypertrophic molecular biomarkers were elevated, and the potential pathways were explored by transcriptome analysis. Results: Actn2 suppression impaired calcium uptake and increased hypertrophy in H9c2 cells under dexamethasone treatment. Concomitantly, hypertrophic molecular biomarkers were also elevated in Actn2-suppressed cells. Further transcriptome analysis and Western blotting data suggested that Actn2 suppression led to the excessive activation of the MAPK pathway and ERK cascade. In vitro pharmaceutical intervention with ERK inhibitors could partially reverse the morphological changes and inhibit the excessive cardiac hypertrophic molecular biomarkers in H9c2 cells. Conclusion: Our study revealed a functional role of ACTN2 under chronic stress, loss of ACTN2 function accelerated H9c2 hypertrophy through ERK signaling. A commercial drug, Ibudilast, was identified to reverse cell hypertrophy in vitro. [ABSTRACT FROM AUTHOR]

Purpose: Cardiac abnormalities are common in patients with acromegaly, contributing to the increased morbidity and mortality. Cardiac magnetic resonance (CMR) is the gold standard for measuring cardiac morpho-functional changes. This study aims to detect cardiac alterations in acromegaly through CMR, even when the disease is adequately controlled. Methods: In this, multicentre, case-control study, we compared consecutive patients with acromegaly, cured after surgery or requiring medical treatment, with matched controls recruited among patients harbouring non-functioning adrenal incidentalomas. Results: We included 20 patients with acromegaly (7 females, mean age 50 years) and 17 controls. Indexed left ventricular-end-diastolic volume (LV-EDVi) and LV-end-systolic volume (LV-ESVi) were higher in patients than in controls (p < 0.001), as were left ventricular mass (LVMi) (p = 0.001) and LV-stroke volume (LV-SVi) (p = 0.028). Right ventricle (RV) EDVi and ESVi were higher, whereas RV-ejection fraction (RV-EF) was lower (p = 0.002) in patients than in controls (p < 0.001). No significant differences were observed in the prevalence of cardiometabolic comorbidities, including hypertension, glucose and lipid metabolism impairment, obstructive sleep apnoea syndrome, and obesity. IGF1 x upper limit of normal significantly predicted LVMi (b = 0.575; p = 0.008). Subgroup analysis showed higher LVMi (p = 0.025) and interventricular septum thickness (p = 0.003) in male than female patients, even after adjusting cardiac parameters for confounding factors. Conclusions: The CMR analysis reveals a cluster of biventricular structural and functional impairment in acromegaly, even when the biochemical control if achieved. These findings appear specifically triggered by the exposure to GH-IGF1 excess and show sex-related differences advocating a possible interaction with sex hormones in cardiac disease progression. [ABSTRACT FROM AUTHOR]

The most common causes of death in acromegaly are cardiovascular diseases (about 60%). Heart arrhythmias and conduction disorders lead to sudden cardiac death (SCD). In this article, we described a clinical case about preventing SCD in a patient with acromegaly. We identified in this patient predictors of SCD: severe left ventricular hypertrophy, the signs of myocardial fibrosis, decreased systolic function of the left ventricular myocardium, ventricular rhythm disturbances, and heart failure. Patients with acromegaly have higher risk of heart arrhythmias due to development acromegalic cardiomyopathy with includes: left ventricular hypertrophy, diastolic and systolic dysfunction, myocardial fibrosis and electrical disturbances of the myocardium. The main limitation is the lack of special clinical recommendations for the management of this group of patients. Current recommendations based on a standard algorithm and do not consider specificity of acromegalic cardiomyopathy.

Cardiac hypertrophy, worldwide known as an adaptive functional compensatory state of myocardial stress, is mainly believed to proceed to severe heart diseases, even to sudden death. Emerging studies have explored the microRNA alteration during hypertrophy. However, the mechanisms of microRNAs involved in cardiac hypertrophy are still uncertain. We studied young rats to establish abdominal aorta coarctation (AAC) for 4 weeks. With the significant downregulated cardiac function and upregulated hypertrophic biomarkers, AAC‐induced rats showed enlarged myocardiocytes and alterations in microRNAs, especially downregulated miR‐31‐5p. miR‐31‐5p targets the 3′UTR of Nfatc2ip and inhibits myocardial hypertrophy in vitro and in vivo. Furthermore, we verified that Nfatc2ip is necessary and sufficient for cardiac hypertrophy in neonatal rat cardiomyocytes. Moreover, we found miR‐31‐5p inhibited the colocalization of Nfatc2ip and hypertrophic gene β‐Mhc. Luciferase assay and ChiP‐qPCR test demonstrated that Nfatc2ip binded to the core‐promoter of β‐Mhc and enhanced its transcriptional activity. Above all, our study found a new pathway, mir‐31‐5p/Nfatc2ip/β‐Mhc, which is involved in cardiac hypertrophy, suggesting a potential target for intervention of cardiac hypertrophy. [ABSTRACT FROM AUTHOR]

Nestin is a unique intermediate filament expressed for a short period in the developing heart. It was also documented in several cell types of the adult myocardium under pathological conditions such as myocardial infarction or fibrosis. However, circumstances of nestin re-occurrence in the diseased or aging heart have not been elucidated yet. In this work we immunohistochemically detected nestin to determine its expression and distribution pattern in the left ventricular myocardium of normotensive Wistar Kyoto (WKY) rats and in the hypertrophic ones of spontaneously hypertensive (SHR) rats, both at the age of 1 and 1.5 year. No nestin+ cells were identified in the intact myocardium of 1-year-old WKY rats, whereas in the aged 1.5-year-old WKY rats nestin+ endothelial cells in some blood vessels were discovered. In the hypertrophic myocardium of all SHR rats, nestin was rarely detected in desmin+ vimentin− cardiomyocytes and in some vimentin+ interstitial cells often accumulated in clusters, varying in intensity of desmin immunoreactivity. Moreover, nestin was infrequently expressed in the endothelial cells of some myocardial blood vessels in 1-year-old SHR rats, but not in 1.5-year-old ones. Quantitative image analysis of nestin expression in the myocardium confirmed significant increase in 1.5-year-old WKY rats and in SHR rats of both ages compared to the intact 1-year-old WKY rats. This study firstly documents nestin re-expression indicating cytoskeletal remodelling in different cell types of the aging intact and chronically pressure over-loaded hypertrophied myocardium. Our findings confirm nestin involvement in complex changes during myocardial hypertrophy and progressive aging. [ABSTRACT FROM AUTHOR]

Pressure overload-induced hypertrophy compromises cardiac stretch-induced compliance (SIC) after acute volume overload (AVO). We hypothesized that SIC could be enhanced by physiological hypertrophy induced by pregnancy's chronic volume overload. This study evaluated SIC-cardiac adaptation in pregnant women with or without cardiovascular risk (CVR) factors. Thirty-seven women (1st trimester, 1stT) and a separate group of 31 (3rd trimester, 3rdT) women [healthy or with CVR factors (obesity and/or hypertension and/or with gestational diabetes)] underwent echocardiography determination of left ventricular end-diastolic volume (LVEDV) and E/e' before (T0), immediately after (T1), and 15 min after (T2; SIC) AVO induced by passive leg elevation. Blood samples for NT-proBNP quantification were collected before and after the AVO. Acute leg elevation significantly increased inferior vena cava diameter and stroke volume from T0 to T1 in both 1stT and 3rdT, confirming AVO. LVEDV and E/e' also increased immediately after AVO (T1) in both 1stT and 3rdT. SIC adaptation (T2, 15 min after AVO) significantly decreased E/e' in both trimesters, with additional expansion of LVEDV only in the 1stT. NT-pro-BNP increased slightly after AVO but only in the 1stT. CVR factors, but not parity or age, significantly impacted SIC cardiac adaptation. A distinct functional response to SIC was observed between 1stT and 3rdT, which was influenced by CVR factors. The LV of 3rdT pregnant women was hypertrophied, showing a structural limitation to dilate with AVO, whereas the lower LV filling pressure values suggest increased diastolic compliance. NEW & NOTEWORTHY The sudden increase of volume overload triggers an acute myocardial stretch characterized by an immediate rise in contractility by the Frank-Starling mechanism, followed by a progressive increase known as the slow force response. The present study is the first to characterize echocardiographically the stretch-induced compliance (SIC) mechanism in the context of physiological hypertrophy induced by pregnancy. A distinct functional adaptation to SIC was observed between first and third trimesters, which was influenced by cardiovascular risk factors. [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]

The early myocardial response of hypertension is an elevation of angiotensin‐II (Ang‐II) concentration, leading to heart failure and cardiac hypertrophy. This hypertrophic event of the heart is mediated by the interaction of Ang type 1 receptors (AT‐R1), thereby modulating NADPH oxidase activity in cardiomyocytes, which alters redox status in cardiomyocytes. Ellagic acid (EA) has anti‐inflammatory and anti‐oxidative capacities. Thus, EA has potential preventive effects on cardiovascular diseases and diabetes. In the last decades, because the protective effect of EA on Ang‐II‐induced hypertrophic responses is unclear, this study aims to investigate the protective effect of EA in cardiomyocytes. H9c2 cells were treated to Ang‐II 1 μM for 24 h to induce cellular damage. We found that EA protected against Ang‐II‐increased cell surface area and pro‐hypertrophic gene expression in H9c2. EA reduced Ang‐II‐caused AT‐R1 upregulation, thereby inhibiting oxidative stress NADPH oxidase activation. EA mitigated Ang‐II‐enhanced p38 and extracellular‐signal‐regulated kinase (ERK) phosphorylation. Moreover, EA treatment under Ang‐II stimulation also reversed NF‐κB activity and iNOS expression. This study shows that EA protects against Ang‐II‐induced myocardial hypertrophy and attenuates oxidative stress through reactive oxygen species‐mediated mitogen‐activated protein kinase signaling pathways in H9c2 cells. Thus, EA may be an effective compound for preventing Ang‐II‐induced myocardial hypertrophy. [ABSTRACT FROM AUTHOR]

In rats decreased bioavailability of nitric oxide induces oxidative stress and right heart failure. Oxidative stress can activate matrix metalloproteinase-2 (MMP2). We addressed the question whether increasing oxidative defense by administration of the SOD mimetic Tempol or direct inhibition of MMP2 activity by SB-3CT mitigates right heart failure. Rats received l-NAME for four weeks and during week three and four treatment groups received either Tempol or SB-3CT in addition. After four weeks heart function was analyzed by echocardiography, organ weights and expression of NPPB and COL1A1 were analyzed, oxidative stress was monitored by DHE-staining and MMP2 activity was quantified by proteolytic auto-activation, zymography, and troponin I degradation. l-NAME induced oxidative stress and MMP2 activity stronger in the right ventricle than in the left ventricle. Troponin I, a MMP2 substrate, was degraded in right ventricles. Tempol reduced oxidative stress and preferentially affected the expression of fibrotic genes (i.e. COL1A1) and fibrosis. Tempol and SB-3CT mitigated right but not left ventricular hypertrophy. Neither SB-3CT nor Tempol alone strongly improved right ventricular function. In conclusion, both MMP2 activity and oxidative stress contribute to right ventricular failure but neither is MMP2 activation linked to oxidative stress nor does oxidative stress and MMP2 activity have common targets.

Background and aimsDespite different etiopathogenesis, Fabry Disease cardiomyopathy (FDc) and sarcomeric hypertrophic cardiomyopathy (HCM) share a similar hypertrophic phenotype, including anomalies of the mitral valve apparatus (AMVA). Some of these anomalies have also been described in the pre-hypertrophic stage of both diseases. This cardiovascular magnetic resonance (CMR) study aimed to: (i) compare AMVA between FDc and HCM with a similar degree of left ventricular hypertrophy (LVH), to add new insights into differential diagnosis; (ii) assess whether AMVA represent an early and progressive alteration in FDc; (iii) propose simple and potentially reproducible measurements of AMVA.MethodsThis observational, retrospective study enrolled: (i) 80 Fabry patients, divided into three groups with increasing severity of cardiac phenotype (20 patients LVH-/normal T1, 20 patients LVH-/low T1 and 40 patients LVH+), and (ii) 40 patients with HCM. All patients underwent CMR. The LVH + FDc and the HCM groups were matched for age, sex, body surface area and left ventricular (LV) mass. The following AMVA were measured on cine images: papillary muscles (PMs) hypertrophy (maximal diameter (Dmax) of anterolateral (Al) and posteromedial (Pm) PM), apical displacement, anteriorization of Al PM and anterior mitral valve leaflet (AMVL) elongation. Reference values for defining AMVA were derived from a matched healthy control group (n = 40).ResultsBoth HCM and FDc LVH + patients showed PMs hypertrophy, with a greater degree in the FDc LVH + group [Dmax Al PM 16 ± 3.4 vs. 15 ± 3.1 mm, p 0.017; Dmax Pm PM 14 ± 4.0 vs.12 mm (10.0–14.0), p 0.039] As compared to controls, both HCM and FDc LVH + patients showed PMs apical displacement (HCM 83% vs. healthy volunteers 8%, p

Istianah Purnamasari, Yuyun Sri Wahyuni, Hernawati Basir Department of Pharmacy, Faculty of Medicine and Health Science, Universitas Muhammadiyah Makassar, Makassar, South Sulawesi, IndonesiaCorrespondence: Istianah Purnamasari, Department of Pharmacy, Faculty of Medicine and Health Science, Universitas Muhammadiyah Makassar, Makassar, South Sulawesi, Indonesia, Email istianahpurnamasari@unismuh.ac.id

Myocardial hypertrophy is the most common condition that accompanies heart development in children. Transcriptional gene expression regulating pathways play a critical role both in cardiac embryogenesis and in the pathogenesis of congenital hypertrophic cardiomyopathy, neonatal posthypoxic myocardial hypertrophy, and congenital heart diseases. This paper describes the state of cardiac gene expression and potential pharmacological modulators at different transcriptional levels. An experimental model of perinatal cardiac hypoxia showed the downregulated expression of genes responsible for cardiac muscle integrity and overexpressed genes associated with energy metabolism and apoptosis, which may provide a basis for a therapeutic approach. Current evidence suggests that RNA drugs, theaflavin, neuraminidase, proton pumps, and histone deacetylase inhibitors are promising pharmacological agents in progressive cardiac hypertrophy. The different points of application of the above drugs make combined use possible, potentiating the effects of inhibition in specific signaling pathways. The special role of N-acetyl cysteine in both the inhibition of several signaling pathways and the reduction of oxidative stress was emphasized. [ABSTRACT FROM AUTHOR]

Objective: Systemic lupus erythematosus (SLE) is a multisystem‐involved, highly heterogeneous autoimmune disease with diverse clinical manifestations. We report an extremely rare case of SLE with severe diffuse myocardial hypertrophy. Methods: The patientʼs echocardiography and cardiac magnetic resonance imaging (CMR) results indicated diffuse myocardial hypertrophy. After excluding coronary atherosclerosis, hypertensive cardiomyopathy, drug toxicity, and other causes, the patient was diagnosed with SLE‐specific cardiomyopathy. Medications such as hormones, antimalarials, immunosuppressants, and biologics were administered. Results: Ancillary test results were as follows: hs‐cTnI: 0.054 ng/mL (0–0.016); NTproBNP: 1594.0 pg/mL (<150); A contrast‐enhanced CMR revealed the diffuse thickening of the left ventricular wall with multiple abnormal enhancements, reduced left ventricular systolic and diastolic function, and moderate amount of pericardial effusion. Endomyocardial myocardial biopsy was performed, showing cardiomyocyte hypertrophy and degeneration, and no changes in myocarditis or amyloidosis. The pathology viewed by electron microscopy showed increased intracellular glycogen in the myocardium, and no hydroxychloroquine‐associated damage in the myocardium. The 24‐h ambulatory blood pressure and contrast‐enhanced computed tomography of coronary arteries were normal. The diagnosis of SLE‐specific cardiomyopathy was clear. The myocardial hypertrophy showed reversible alleviation following treatment with high‐dose corticosteroids. CMR results before and after treatment were as follows: interventricular septum, pretreatment (28) versus post‐treatment (22) mm; left ventricular inferior wall, pretreatment (18–21) versus post‐treatment (12–14) mm; left ventricular lateral wall, pretreatment (17–18) versus post‐treatment (10–12) mm; pericardial effusion (left ventricular lateral wall), pretreatment (25) versus post‐treatment (12) mm; left ventricular ejection fraction, pretreatment (38.9%) versus post‐treatment (66%). Conclusion: Myocardial hypertrophy may be an important sign of active and prognostic assessment in SLE diagnosis and management. Similarly, when encountering cases of myocardial hypertrophy, the possibility of autoimmune disease should be considered in addition to common causes. Highlights: We report a rare case of severe diffuse myocardial hypertrophy directly caused by systemic lupus erythematosus (SLE), secondary to severe heart failure.Reversible improvement in myocardial hypertrophy occurred after high‐dose corticosteroid therapy.SLE is associated with a reversible form of cardiomyopathy.Myocardial hypertrophy may be an important sign of active and prognostic assessment of SLE.When encountering cases of myocardial hypertrophy, the possibility of autoimmune disease should be considered in addition to the common causes. [ABSTRACT FROM AUTHOR]

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End-stage renal disease (ESRD) is a common but profound clinical condition, and it is associated with extremely increased morbidity and mortality. ESRD can represent four major echocardiographic findings―myocardial hypertrophy, heart failure, valvular calcification, and pericardial effusion. Multiple factors interplay leading to these abnormalities, including pressure/volume overload, oxidative stress, and neurohormonal imbalances. Uremic cardiomyopathy is characterized by left ventricular (LV) hypertrophy and marked diastolic dysfunction. In ESRD patients on hemodialysis, LV geometry is changeable bidirectionally between concentric and eccentric hypertrophy, depending upon changes in corporal fluid volume and arterial pressure, which eventually results in a characteristic of LV systolic dysfunction. Speckle tracking echocardiography enabling to detect subclinical disease might help prevent future advancement to heart failure. Heart valve calcification also is common in ESRD, keeping in mind which progresses faster than expected. In a modern era, pericardial effusion observed in ESRD patients tends to result from volume overload, rather than pericarditis. In this review, we introduce and discuss those four echocardiography-assessed findings of ESRD, with which known and conceivable pathophysiologies for each are incorporated. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the ability of fast strain-encoded (SENC) cardiac magnetic resonance (CMR) derived myocardial strain and native T1 mapping to discriminate between hypertrophic cardiomyopathy (HCM) and cardiac amyloidosis. Methods: Ninety nine patients (57 with hypertrophic cardiomyopathy and 42 with cardiac amyloidosis) were systematically analysed. LV-ejection fraction, LV-mass index, septal wall thickness and native T1 mapping values were assessed. In addition, global circumferential and longitudinal strain and segmental circumferential and longitudinal strain in basal, mid-ventricular, and apical segments were calculated. A ratio was built by dividing native T1 values by basal segmental strain (T1-to-basal segmental strain ratio). Results: Myocardial strain was equally distributed in apical and basal segments in HCM patients, whereas an apical sparing with less impaired apical strain was noticed in cardiac amyloidosis (apical-to-basal-ratio of 1.01 ± 0.23 versus 1.20 ± 0.28, p < 0.001). T1 values were significantly higher in amyloidosis compared to HCM patients (1170.7 ± 66.4 ms versus 1078.3 ± 57.4ms, p < 0.001). The T1-to-basal segmental strain ratio exhibited high accuracy for the differentiation between the two clinical entities (Sensitivity = 85%, Specificity = 77%, AUC = 0.90, 95% CI = 0.81–0.95, p < 0.001). Multivariable analysis showed that age and the T1-to-basal-strain-ratio were the most robust factors for the differentiation between HCM and cardiac amyloidosis. Conclusion: The T1-to-basal-segmental strain ratio, combining information from segmental circumferential and longitudinal strain and native T1 mapping aids the differentiation between HCM and cardiac amyloidosis with high accuracy and within a fast CMR protocol, obviating the need for contrast agent administration. [ABSTRACT FROM AUTHOR]

Background: Cardiac lesions are responsible for approximately 60-70% of sudden deaths. Histopathological examination of heart on autopsy plays an essential role in determining the cause of death. Hence, the present study was undertaken to study the histopathological spectrum of uncommon lesions in the heart and blood vessels that arise from heart, which either proved to be a primary or contributory to the cause of deaths in clinical autopsies. Method: This prospective study was conducted in the Department of Pathology of a Tertiary care hospital over a period of one year from Jan 2020 to Dec 2020. During the study period, a total of 19 cases with uncommon lesions in heart and aorta were studied. The available clinical data had been collected from hospital records in these clinical autopsy cases. Cases of myocardial infarction were excluded. Results: Out of 19 cases, 11 cases were found in the age group of 15-40 years and 8 cases were of 40-50 years. Among 19 cases, 9 (47.4%) were inflammatory lesions, 4 (21.1%) cases of degenerative changes like fatty infiltration of heart, 2 cases of neoplastic etiology and one case each of aneurysm of sinus of Valsalva, mural thrombi in heart, myocardial hypertrophy and one case of aortic dissection. Conclusion: In the present study, inflammatory lesions (myocarditis and tuberculous myocarditis) was the commonest histopathologic finding followed by fatty infiltration of the heart. Other lesions like aortic dissection and aneurysm of sinus of Valsalva were the uncommon lesions seen in our study. Thus, histopathology in autopsy plays a vital role in the study of some of the rare cardiac lesions contributing to the knowledge of pathology. [ABSTRACT FROM AUTHOR]

BackgroundMachine learning is increasingly being used to diagnose and treat various diseases, including cardiovascular diseases. Automatic image analysis can expedite tissue analysis and save time. However, using machine learning is limited among researchers due to the requirement of technical expertise. By offering extensible features through plugins and scripts, machine-learning platforms make these techniques more accessible to researchers with limited programming knowledge. The misuse of anabolic-androgenic steroids is prevalent, particularly among athletes and bodybuilders, and there is strong evidence of their detrimental effects on ventricular myocardial capillaries and muscle cells. However, most studies rely on qualitative data, which can lead to bias and limited reliability. We present a user-friendly approach using machine learning algorithms to measure the effects of exercise and anabolic-androgenic steroids on cardiac ventricular capillaries and myocytes in an experimental animal model.MethodMale Wistar rats were divided into four groups (n = 28): control, exercise-only, anabolic-androgenic steroid-alone, and exercise with anabolic-androgenic steroid. Histopathological analysis of heart tissue was conducted, with images processed and analyzed using the Trainable Weka Segmentation plugin in Fiji software. Machine learning classifiers were trained to segment capillary and myocyte nuclei structures, enabling quantitative morphological measurements.ResultsExercise significantly increased capillary density compared to other groups. However, in the exercise + anabolic-androgenic steroid group, steroid use counteracted this effect. Anabolic-androgenic steroid alone did not significantly impact capillary density compared to the control group. Additionally, the exercise group had a significantly shorter intercapillary distance than all other groups. Again, using steroids in the exercise + anabolic-androgenic steroid group diminished this positive effect.ConclusionDespite limited programming skills, researchers can use artificial intelligence techniques to investigate the adverse effects of anabolic steroids on the heart's vascular network and muscle cells. By employing accessible tools like machine learning algorithms and image processing software, histopathological images of capillary and myocyte structures in heart tissues can be analyzed.

Abstract Background Perilipin 5 (Plin5) is well known to maintain the stability of intracellular lipid droplets (LDs) and regulate fatty acid metabolism in oxidative tissues. It is highly expressed in the heart, but its roles have yet to be fully elucidated. Methods Plin5-deficient mice and Plin5/leptin-double-knockout mice were produced, and their histological structures and myocardial functions were observed. Critical proteins related to fatty acid and glucose metabolism were measured in heart tissues, neonatal mouse cardiomyocytes and Plin5-overexpressing H9C2 cells. 2-NBDG was employed to detect glucose uptake. The mitochondria and lipid contents were observed by MitoTracker and BODIPY 493/503 staining in neonatal mouse cardiomyocytes. Results Plin5 deficiency impaired glucose utilization and caused insulin resistance in mouse cardiomyocytes, particularly in the presence of fatty acids (FAs). Additionally, Plin5 deficiency increased the NADH content and elevated the expression of lactate dehydrogenase (LDHA) in cardiomyocytes, which resulted in increased lactate production. Moreover, when fatty acid oxidation was blocked by etomoxir or LDHA was inhibited by GSK2837808A in Plin5-deficient cardiomyocytes, glucose utilization was improved. Leptin-deficient mice exhibited myocardial hypertrophy, insulin resistance and altered substrate utilization, and Plin5 deficiency exacerbated myocardial hypertrophy in leptin-deficient mice. Conclusion Our results demonstrated that Plin5 plays a critical role in coordinating fatty acid and glucose oxidation in cardiomyocytes, providing a potential target for the treatment of metabolic disorders in the heart. Graphic abstract

The article describes major milestones in acknowledgment of pathophysiological relationship between heart and kidneys since Ancient Egypt till our time and history of term cardiorenal syndrome (CRS). First references about kidney and heart functions could be dated to 13 BC when Hippocrates mentioned them. In the XIV century Gentile da Foligno proposed a hypothesis about functional interconnection between heart and kidneys. In the XVIII century Richard Bright described the link between myocardial hypertrophy and kidneys diseases. Frederic Justin Collet was the first one who used the term cardiorenal in his article in 1903. In Russia, I.I. Stolnikov conducted his experiments about myocardial hypertrophy and kidneys ischemia in 1880. Famous Russian internist, E.M. Tareev, devoted several paragraphs to cardiorenal interactions in his fundamental manuals Anemia in Brights disease (1929) and Hypertension (1948). The research on this topic was continued by Tareevs followers: N.A. Mukhin, V.S. Moiseev, more recent successors Zh.D. Kobalava, S.V. Moiseev, V.V. Fomin, S.V. Villevalde and others. Their contribution resulted in development of first Russian clinical guidelines on cardio and nephroprotection in CRS in 2014. In 2008 consensus of Acute Disease Quality Initiative summarized current experience on CRS. Today, research on controversial classification questions, biomarkers and other aspects of CRS continues.

Hypertrophic cardiomyopathy is characterized by genetic and phenotypic heterogeneity which manifests in different variants of localization and extent of myocardial hypertrophy.Aim: to evaluate specifics of left ventricular hypertrophy, the prevalence and characteristics of clinical and instrumental features of phenotypic variants of hypertrophic cardiomyopathy.Materials and methods. The study includes 295 patients with hypertrophic cardiomyopathy aged 18 to 88 years (60.3±13.4 years), 183 men (62 %), and women 112 (38 %). The diagnosis of which was established by 2D echocardiography. The severity, localization and extent of myocardial hypertrophy, the maximum thickness of the hypertrophied segment, left ventricular myocardial mass, left ventricular myocardial mass index, the presence and severity of mid-ventricular and left ventricular outflow tract obstruction were evaluated. Depending on the predominant localization and extent of hypertrophy, patients were divided into 8 groups according to the recommendations for hypertrophic cardiomyopathy of the Ministry of Health of the Russian Federation. The analysis and comparison of the obtained results are carried out.Results. The average duration of the disease is 10.5±7.52 years. The mean values of the body mass index in patients — 28.2±2.82 kg/m2. The phenotype with basal hypertrophy of the septum (n=130, 44.1 %), group 1 was most often noted. In 47 (15.9 %) patients, hypertrophy of the septum of “reverse curve” (2 group) was detected, in 41 (13.9 %) — “neutral septum” (3 group), in 36 (12.2 %) — symmetrical hypertrophy of the left ventricle (8 group), 11 (3.7 %) of patients had combined hypertrophy of the septum and other parts of the left or right ventricle (4 group) and the free left ventricular wall (7 group), in 10 (3.4 %) — middle ventricular hypertrophy of the left ventricle (6 group) and in 9 (3.1 %) — apical hypertrophy (5 group). The highest value of the maximum thickness of the myocardium was noted in patients of the 6th group 19.3 (1920.4 mm). Mid-ventricular obstruction was detected in group 6 (90 %), left ventricular outflow tract obstruction was more often registered in groups 4 and 8 (81.8 % and 77.8 %), and less often in group 5 (22.2 %) (p

BACKGROUND: Histone modification is a reversible post-translational modification that acts as a marker of transcriptional activation or inhibition and controls cell metabolism, damage, and repair. Deacetylation, as one of the histone posttranslational modifications, plays an important role in the occurrence and development of cardiovascular diseases. OBJECTIVE: To mainly review the mechanisms of histone deacetylation in atherosclerosis, myocardial hypertrophy, heart failure, myocardial infarction, and hypertension, in order to further understand the pathological processes related to the occurrence and development of cardiovascular diseases, providing theoretical reference for the diagnosis, treatment and prognosis of cardiovascular diseases. METHODS: Related articles published from 1979 to 2022 were retrieved from PubMed, Web of Science and CNKI database. The keywords were “histone, histone modification, histone acetylation, histone deacetylation, histone transacetylase, histone deacetylase, cardiovascular, atherosclerosis, cardiac hypertrophy, heart failure, myocardial infarction, hypertension” in English and Chinese. Ultimately, we included 64 articles for review. RESULTS AND CONCLUSION: Histone acetylation modifications occur mainly at the more conserved N-terminal lysine residues of core histones and are regulated synergistically by histone acetyltransferases and histone deacetylases, which have emerged as an important form of epigenetic regulation. Histone deacetylation modifications regulate the occurrence and development of cardiovascular diseases and the following conclusions can be drawn: (1) At the protein level, histone deacetylation modifications increase the diversity and complexity of mechanisms between cellular pathways, mainly by changing the localization, activity or function of proteins, which then affect a variety of important cellular life activities, thus playing an important role in the diagnosis, treatment and prognosis of cardiovascular diseases. (2) Histone acetyltransferase and histone deacetylase molecules are closely related to cardiovascular diseases such as atherosclerosis, myocardial hypertrophy, myocardial infarction and hypertension, and their corresponding inhibitors can be used as targeted drugs for these diseases. (3) Research on histone acetylation and deacetylation modifications in cardiovascular diseases is still at the basic research stage and the specific mechanisms of histone deacetylation modifications in some diseases are still being investigated. As research progresses, new breakthroughs in histone acetylation modifications are expected in the treatment of cardiovascular disease and in clinical translation. [ABSTRACT FROM AUTHOR]

The research purpose was to investigate the effects and the underlying molecular mechanisms of bovine bone gelatin peptides (BGP) on myocardial hypertrophy in spontaneously hypertensive rats (SHR). BGP relieved myocardial hypertrophy and fibrosis in SHR rats in a dose-dependent manner by reducing the left ventricular mass index, myocardial cell diameter, myocardial fibrosis area, and levels of myocardial hypertrophy markers (atrial natriuretic and brain natriuretic peptide). Label-free quantitative proteomics analysis showed that long-term administration of BGP changed the left ventricle proteomes of SHR. The 37 differentially expressed proteins in the high-dose BGP group participated in multiple signaling pathways associated with cardiac hypertrophy and fibrosis indicating that BGP could play a cardioprotective effect on SHR rats by targeting multiple signaling pathways. Further validation experiments showed that a high dose of BGP inhibited the expression of phosphoinositide 3-kinase (Pi3k), phosphorylated protein kinase B (p-Akt), and transforming growth factor-beta 1 (TGF-β1) in the myocardial tissue of SHR rats. Together, BGP could be an effective candidate for functional nutritional supplements to inhibit myocardial hypertrophy and fibrosis by negatively regulating the TGF-β1 and Pi3k/Akt signaling pathways. [ABSTRACT FROM AUTHOR]

Background. Cardiovascular manifestations are rated first among the symptoms of hypothyroidism. Since the highest prevalence of both coronary heart disease (CHD) and hypothyroidism is observed in the age group over 50 years old, the problem of combination of these nosologies in older people is increasing. Aim of the study is to investigate the structural and functional state of the left ventricular myocardium in hypothyroidism and CHD associated with chronic systemic inflammation. Materials and methods. To reach the objectives of the study, a randomized controlled clinical trial has been conducted in parallel groups of patients with hypothyroidism, CHD and combination of both. To form the main group, a screening analysis of 556 medical histories of patients with hypothyroidism and CHD during the period of 2006–2015 has been made, which were selected for further study. Results. It has been found that myocardial hypertrophy develops in all groups of patients, a decrease in thyroid function leads to remodeling of the left ventricular myocardium with the development of eccentric hypertrophy and the progression of systolic heart failure in comorbidity. A direct correlation between reduced ejection fraction and elevated interleukin-8 level has been detected. Evaluation of the state of chronic systemic inflammation revealed a significant increase in the level of interleukin-8 in patients with coronary heart disease associated with hypothyroidism (7.66 ± 2.18 pg/ml; p

Systemic and pulmonary arterial hypertension (PAH) can induce left and right ventricular hypertrophy, respectively, but common therapeutic targets for both left and right hypertrophy are limited. In this study, we attempt to explore potential common therapeutic targets and screen out potential target drugs for further study. Cardiac mRNA expression profiles in mice with transverse aortic constriction (TAC) and pulmonary arterial constriction (PAC) are obtained from online databases. After bioinformatics analyses, we generate TAC and PAC mouse models to validate the phenotypes of cardiac remodelling as well as the identified hub genes. Bioinformatics analyses show that there are 214 independent differentially expressed genes (DEGs) in GSE136308 (TAC related) and 2607 independent DEGs in GSE30922 (PAC related), while 547 shared DEGs are associated with the function of the extracellular matrix (ECM) or involved in the PI3K-Akt signaling pathway, cytokine-cytokine receptor interactions, and ECM-receptor interactions. We identifyd Fn1, Il6, Col1a1, Igf1, Col1a2, Timp1, Col3a1, Cd44, Ctgf and Postn as hub genes of the shared DEGs, and most of them are associated with myocardial fibrosis. Those hub genes and phenotypes of cardiac remodelling are validated in our TAC and PAC mouse models. Furthermore, we identify dehydroisoandrosterone (DHEA), iloprost and 4,5-dianilinophthalimide (DAPH) as potential therapeutic drugs targeting both left and right ventricular hypertrophy and validate the effect of DHEA. These findings suggest that DHEA could be an effective drug for pressure overload-induced left or right ventricular hypertrophy by regulating the shared hub differentially expressed genes associated with fibrosis.

Aim. To assess the incidence of myocarditis in patients with primary myocardial hypertrophy and to study its contribution to the disease course.Material and methods. The study included 100 patients with primary left ventricular myocardial hypertrophy, 52 men and 48 women (mean age, 51,5±15,7 years; followup period 10,4 [2,1; 36,1] months). All patients underwent electrocardiography, 24-hour electrocardiographic monitoring, echocardiography, as well as DNA analysis (n=96), myocardium pathological study (n=29), cardiac magnetic resonance imaging (n=31), cardiac multislice computed tomography (n=26), assessment of anti-cardiac antibodies (n=43), free light chain level in serum and urine by immunofixation method (n=10); 99mTc-pyrophosphate myocardial scintigraphy (n=5); biopsy of the rectal mucosa and/or subcutaneous fat for amyloid (n=9).Results. In 68%, true (sarcomeric) hypertrophic cardiomyopathy (HCM) was diagnosed, in 16% — amyloidosis with cardiac involvement, in 10% — storage diseases, in 3% — neuromuscular diseases, in 2% — myocardial hypertrophy was combined with severe restriction (mixed phenotype), and in 1% — LEOPARD syndrome. Concomitant myocarditis was diagnosed in 30% of patients. In HCM, myocarditis was detected in 31% of cases. These patients had a significantly higher heart failure class (heart failure class 3 [2; 3] vs 2 [1; 3], p=0,026) and mortality (33,3% vs 6,4%, p=0,01). In amyloidosis, the incidence of myocarditis was 31,3%. In these patients, ventricular tachycardia was observed significantly more often: 80,0% vs 18,2% (p=0,036). The prevalence of concomitant myocarditis in the subgroup of storage diseases was 30%: 2 patients with Fabry disease and 1 patient with Danon disease. Of the three patients with neuromuscular diseases, myocarditis was diagnosed in 1. In the subgroups with the restrictive phenotype and LEOPARD syndrome, no cases of myocarditis were recorded. Treatment of myocarditis made it possible to stabilize the patients' condition.Conclusion. Concomitant myocarditis led to heart failure progression, worsening ventricular arrhythmias and, as a consequence, an increased risk of sudden cardiac death. It is necessary to actively diagnose and treat myocarditis in patients with primary myocardial hypertrophy.

Objective: To evaluate the cardioprotective effect of Sfrp1 in angiotensin II-induced cardiac hypertrophy and to explore its possible mechanism related to autophagy and Wnt signaling pathway. Methods: Sfrp1 was introduced into Ang II-induced hypertrophic H9C2 cardiomyocytes by recombinant AAV9 vector. Cell viability was measured by CCK8. The apoptosis rate was detected by flow cytometry. Changes in the size of hypertrophic cells were recorded by microphotography. Western blot was used to detect the protein expression of Sfrp1, Bcl-2, Bax, CytC, Caspase-3, P62, ATG5, Beclin, LC3, β -catenin and DVL1. The mRNA expression of β-catenin and DVL1 was detected by qRT-PCR. The autophagy inhibitor 3-MA was also used to verify the involvement of autophagy during treatment. Results: (1) Sfrp1 was successfully transfected into H9C2 cells, and its overexpression reduced cardiac hypertrophy. (2) AAV9-Sfrp1 pretreatment can reduce the apoptosis of hypertrophic myocardium and reverse the expression of autophagy-related proteins ( p62, ATG5, Beclin, LC3 ) in Ang II group. (3) The role of autophagy in the treatment of cardiac hypertrophy was confirmed by the autophagy inhibitor 3-MA. (4) The activated Wnt signaling ( β-catenin, DVL1 ) was also inhibited by AAV9-Sfrp1. Conclusion: Sfrp1 promotes autophagy through Wnt signaling pathway, thereby protecting cardiomyocytes from hypertrophic injury and apoptosis, which provides an important perspective for the myocardial protection mechanism of Sfrp1 on myocardial hypertrophy. [ABSTRACT FROM AUTHOR]

Necroptosis is a newly discovered mechanism of cell death, and its key regulatory role is attributed to the interaction of receptor-interacting protein kinases (RIPKs) RIPK1 and RIPK3. Ca2+/calmodulin-dependent protein kinase (CaMKII) is a newly discovered RIPK3 substrate, and its alternative splicing plays a fundamental role in cardiovascular diseases. In the present study, we aimed to explore the role and mechanism of necroptosis and alternative splicing of CaMKIIδ in myocardial hypertrophy. Transverse aortic constriction (TAC) was performed on wild-type and knockout mice to establish the model of myocardial hypertrophy. After 3 weeks, echocardiography, cardiac index, cross-sectional area of myocardial cells, hypertrophic gene expression, myocardial damage, and fibers were assessed. Moreover, we detected the levels of inflammatory factors (IL-6 and TNF-α) and examined the expressions of necroptosis-related proteins RIPK3, RIPK1, and phosphorylated MLKL. Meanwhile, we tested the expression levels of splicing factors ASF/SF2 and SC-35 in an attempt to explore CaMKII δ. The relationship between variable splicing disorder and the expression levels of splicing factors ASF/SF2 and SC-35. Further, we also investigated CaMKII activation, oxidative stress, and mitochondrial ultrastructure. In addition, wild-type mice were administered with a recombinant adeno-associated virus (AAV) carrying RIPK3, followed by TAC surgery to construct a model of myocardial hypertrophy, and the above-mentioned indicators were tested after 3 weeks. The results showed that RIPK3 deficiency could alleviate cardiac dysfunction, myocardial injury, aggravation of necrosis, and CaMKII activation induced by TAC surgery in mice with myocardial hypertrophy. Tail vein injection of AAV could reverse cardiac dysfunction, myocardial damage, aggravation of necrosis, and CaMKII activation in mice with myocardial hypertrophy. These results proved that RIPK3 could be used as a molecular intervention target for the prevention and treatment of myocardial hypertrophy. [ABSTRACT FROM AUTHOR]

Long non-coding RNAs (lncRNAs) are non-coding RNA molecules longer than 200 nucleotides that regulate gene expression at the transcriptional, post-transcriptional, and translational levels. Abnormal expression of lncRNAs has been identified in many human diseases. Future improvements in diagnostic, prognostic, and therapeutic techniques will be facilitated by a deeper understanding of disease etiology. Cardiovascular diseases (CVDs) are the main cause of death globally. Cardiac development involves lncRNAs, and their abnormalities are linked to many CVDs. This review examines the relationship and function of lncRNA in a variety of CVDs, including atherosclerosis, myocardial infarction, myocardial hypertrophy, and heart failure. Therein, the potential utilization of lncRNAs in clinical diagnostic, prognostic, and therapeutic applications will also be discussed. [ABSTRACT FROM AUTHOR]

Background: Perilipin 5 (Plin5) is well known to maintain the stability of intracellular lipid droplets (LDs) and regulate fatty acid metabolism in oxidative tissues. It is highly expressed in the heart, but its roles have yet to be fully elucidated. Methods: Plin5-deficient mice and Plin5/leptin-double-knockout mice were produced, and their histological structures and myocardial functions were observed. Critical proteins related to fatty acid and glucose metabolism were measured in heart tissues, neonatal mouse cardiomyocytes and Plin5-overexpressing H9C2 cells. 2-NBDG was employed to detect glucose uptake. The mitochondria and lipid contents were observed by MitoTracker and BODIPY 493/503 staining in neonatal mouse cardiomyocytes. Results: Plin5 deficiency impaired glucose utilization and caused insulin resistance in mouse cardiomyocytes, particularly in the presence of fatty acids (FAs). Additionally, Plin5 deficiency increased the NADH content and elevated the expression of lactate dehydrogenase (LDHA) in cardiomyocytes, which resulted in increased lactate production. Moreover, when fatty acid oxidation was blocked by etomoxir or LDHA was inhibited by GSK2837808A in Plin5-deficient cardiomyocytes, glucose utilization was improved. Leptin-deficient mice exhibited myocardial hypertrophy, insulin resistance and altered substrate utilization, and Plin5 deficiency exacerbated myocardial hypertrophy in leptin-deficient mice. Conclusion: Our results demonstrated that Plin5 plays a critical role in coordinating fatty acid and glucose oxidation in cardiomyocytes, providing a potential target for the treatment of metabolic disorders in the heart. [ABSTRACT FROM AUTHOR]

AIM: To explore the beneficial effects and underlying mechanisms of linsitinib (OSI-906) on angiotensin II (Ang II) -induced cardiac hypertrophy in mice. METHODS: Thirty C57BL/6J mice were randomly divided into 3 groups (10 mice each group): control group, model (Ang II)group, and Ang II+OSI-906 group. Myocardial hypertrophy mouse model was constructed by treating with Ang II(2 mg* *kg_1 *d_1) with the subcutaneous injection for 2 weeks, and the Ang II+OSI-906 group was given OSI-906(50 mg/kg) by gastric irrigation on this basis. Using hematoxylin-eosin (HE)staining, the pathological changes of heart tissue of mice were evaluated. Using RT-qPCR, the related mRNA levels of heart tissues of mice were detected. The protein expressions of the AMPK/SIRT3 signaling pathway were detected using Western blot assay. The indicators of oxidative stress, including malondialdehyde(MDA), catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were detected by ELISA kits. RESULTS: Compared with model group, the cardiac mass indexes(HW/BW and HW/TL) were significantly decreased in Ang Il-treated mice with OSI-906-treatment (PVO. 05). Moreover, OSI-906-treatment showed the similar alterations on the pathological changes of heart tissues. The mRNA levels of atrial natriuretic peptide(ANP), brain natriuretic peptide(BNP), and the inflammatory cytokines of tumor necrosis factor-a(TNF-ot), interleukin lp(IL-Ip) and interleukin 6(IL-6) were all significantly down-regulated in the heart tissues of mice in Ang II+OSI-906 group (PV0. 05). Furthermore, the level of MDA was significantly decreased(PVO.01), but the levels of SOD, CAT and GSH-Px were increased (P<0. 05). The phosphorylation of AMP-activated protein kinase (p-AMPK)and silent information regulator 3 (SIRT3) were up-regulated (P<0. 05). Consistently, the mRNA expressions of ANP, BNP and myosin heavy chain (p-MHC) were significantly increased in primary neonatal mice cardiomyocytes treated with Compound C, a blocker of AMPK signaling. CONCLUSION: OSI-906 significantly inhibited Ang Il-induced myocardial inflammation and oxidative stress in mice, and may play a cardioprotective role through the AMPK/SIRT3 signaling pathway. [ABSTRACT FROM AUTHOR]

Myocardial hypertrophy plays a crucial role in cardiovascular disease (CVD) development. Myocardial hypertrophy is an adaptive response by myocardial cells to stress after cardiac injury to maintain cardiac output and function. Angiotensin II (Ang‐II) regulates CVD through the renin‐angiotensin‐aldosterone system, and its signaling in cardiac myocytes leads to excessive reactive oxygen species (ROS) production, oxidative stress, and inflammation. Sesamin (SA), a natural compound in sesame seeds, has anti‐inflammatory and anti‐apoptotic effects. This study investigated whether SA could attenuate hypertrophic damage and oxidative injuries in H9c2 cells under Ang‐II stimulation. We found that SA decreased the cell surface area. Furthermore, Ang‐II treatment reduced Ang‐II‐increased ANP, BNP, and β‐MHC expression. Ang‐II enhanced NADPH oxidase activity, ROS formation, and decreased Superoxide Dismutase (SOD) activity. SA treatment reduces Ang‐II‐caused oxidative injuries. We also found that SA mitigates Ang‐II‐induced apoptosis and pro‐inflammatory responses. In conclusion, SA could attenuate Ang‐II‐induced cardiac hypertrophic injuries by inhibiting oxidative stress, apoptosis, and inflammation in H9c2 cells. Therefore, SA might be a potential supplement for CVD management. [ABSTRACT FROM AUTHOR]

Background: Acromegaly is associated with an increased left ventricular (LV) mass, as reported in echo-based and, more recently, in a few cardiac magnetic resonance imaging (MRI) studies. One possible explanation for this increased LV mass could be water retention and subsequent myocardial edema. Methods: In this prospective cross-sectional study, 26 patients with active acromegaly before and after treatment and 31 controls of comparable age and sex were investigated using cardiac MRI. Cardiac morphology, function, and myocardial tissue characteristics were evaluated. Myocardial T2 relaxation time was used as the main outcome measure of myocardial edema. The study was registered with clinicaltrials.gov (NCT02948322). Results: Patients compared to controls had greater LV mass indexes (58.1 [54.7-68.6] vs 46.0 [41.3-49.8] g/m²; P < .001) and end-diastolic volume (EDV) indexes (97.3 [88-101.2] vs 81.6 [78.1-96.2] mL/m²; P = .0069) and had comparable global contractile function. T2 values were not different between patients and controls. Both intracellular (43.83 [41.0-50.0] vs 34.32 [28.9-38.7] g/m²; P < .001) and extracellular (15.06 [13.5-17.1] vs 11.6 [10.8-12.7] g/m²; P < .001) LV mass indexes were higher in patients compared to controls. Log growth hormone correlated with myocardial mass (r = 0.75; P < .001). Sex, systolic blood pressure (BP), and the presence of acromegaly were predictors of the LV mass index. The extracellular LV mass index was associated with sex and the presence of acromegaly, whereas the intracellular LV mass index was associated with sex, systolic BP, and high-density lipoprotein (HDL) cholesterol. Acromegaly treatment reduced EDV and total and intracellular LV mass indexes without significantly affecting extracellular mass. Conclusion: Acromegaly results in a disease-specific form of LV hypertrophic remodeling, characterized by an increase in both intra- and extracellular mass. The LV mass index and intracellular mass were decreased by treatment. [ABSTRACT FROM AUTHOR]

The androgen receptor (AR) is a member of the family of ligand-activated transcription factors. Selective androgen receptor modulators (SARMs) exert their biological function through complex interactions with the AR. It has been speculated that overexertion of AR signaling cascades as a result of SARM abuse can be a risk factor for the development of various cardiovascular diseases. The present literature review explores the implications of the interaction between SARMs and the AR on cardiovascular health by focusing on the AR structure, function, and mechanisms of action, as well as the current clinical literature on various SARMs. It is shown that SARMs may increase the risk of cardiovascular diseases through implications on the renin–angiotensin system, smooth muscle cells, sympathetic nervous system, lipid profile, inflammation, platelet activity, and various other factors. More research on this topic is necessary as SARM abuse is becoming increasingly common. There is a noticeable lack of clinical trials and literature on the relationship between SARMs, cardiovascular diseases, and the AR. Future in vivo and in vitro studies within this field are vital to understand the mechanisms that underpin these complex interactions and risk factors. [ABSTRACT FROM AUTHOR]