UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.

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.

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.

Herbal-based medications have been used as therapeutic agents for thousands of years, particularly in Asian cultures. It is now well established that these herbal medications contain potent bioactive phytochemicals which exert a plethora of beneficial effects such as those seen on the cardiovascular system. Among the most widely studied of these herbal agents is ginseng, a member of the genus Panax, which has been shown to produce beneficial effects in terms of reducing cardiac pathology, at least in experimental studies. The beneficial effects of ginseng observed in such studies are likely attributable to their constituent ginsenosides, which are steroid-like saponins of which there are at least 100 and which vary according to ginseng species. Many ginseng species such as Panax ginseng (also known as Asian ginseng) and P quinquefolius (North American ginseng) as well as specific ginsenosides have been shown to attenuate hypertrophy as well as other indices of myocardial remodeling in a wide variety of experimental models. Ginkgo biloba on the other hand has been much less studied although the leaf extract of the ancient ginkgo tree has similarly consistently been shown to produce anti-remodeling effects. Ginkgo\'s primary bioactive constituents are thought to be terpene trilactones called ginkgolides, of which there are currently seven known types. Ginkgo and ginkgolides have also been shown to produce anti-remodeling effects as have been shown for ginseng in a variety of experimental models, in some cases via similar mechanisms. Although a common single mechanism for the salutary effects of these compounds is unlikely, there are a number of examples of shared effects including antioxidant and antiapoptotic effects as well as inhibition of pro-hypertrophic intracellular signaling such as that involving the calcineurin pathway which results in the upregulation of pro-hypertrophic genes. Robust clinical evidence represented by large scale phase 3 trials is lacking although there is limited supporting evidence from small trials at least with respect to ginseng. Taken together, both ginseng and ginkgo as well as their bioactive components offer potential as adjuvant therapy for the treatment of myocardial remodeling and heart failure.

UNASSIGNED: Machine 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.
UNASSIGNED: Male 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.
UNASSIGNED: Exercise 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.
UNASSIGNED: Despite 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.

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.
CONCLUSIONS: 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.

OBJECTIVE: The development of cardiac fibrosis (CF) and hypertrophy (CH) can lead to heart failure. Mesenchymal stem cells (MSCs) have shown promise in treating cardiac diseases. However, the relationship between MSCs and splicing factor arginine/serine rich-3 (SFRS3) remains unclear. In this study, our objectives are to investigate the effect of MSCs on SFRS3 expression, and their impact on CF and CH. Additionally, we aim to explore the function of the overexpression of SFRS3 in angiotensin II (Ang II)-treated cardiac fibroblasts (CFBs) and cardiac myocytes (CMCs).
METHODS: Rat cardiac fibroblasts (rCFBs) or rat cardiac myocytes (rCMCs) were co-cultured with rat MSCs (rMSCs). The function of SFRS3 in Ang II-induced rCFBs and rCMCs was studied by overexpressing SFRS3 in these cells, both with and without the presence of rMSCs. We assessed the expression of SFRS3 and evaluated the cell cycle, proliferation and apoptosis of rCFBs and rCMCs. We also measured the levels of interleukin (IL)-β, IL-6 and tumor necrosis factor (TNF)-α and assessed the degree of fibrosis in rCFBs and hypertrophy in rCMCs.
RESULTS: rMSCs induced SFRS3 expression and promoted cell cycle, proliferation, while reducing apoptosis of Ang II-treated rCFBs and rCMCs. Co-culture of rMSCs with these cells also repressed cytokine production and mitigated the fibrosis of rCFBs, as well as hypertrophy of rCMCs triggered by Ang II. Overexpression of SFRS3 in the rCFBs and rCMCs yielded identical effects to rMSC co-culture.
CONCLUSIONS: MSCs may alleviate Ang II-induced cardiac fibrosis and cardiomyocyte hypertrophy by increasing SFRS3 expression in vitro.

OBJECTIVE: To observe the effect of electroacupuncture (EA) at \"Neiguan\"(PC6) on cardiac function, cardiac morphology and transient receptor potential channel (TRPC) protein expressions in myocardial tissue of mice with myocardial hypertrophy, so as to explore its mechanisms underlying improvement of myocardial hypertrophy.
METHODS: Forty-five male C57BL/6 mice were randomly divided into control, model and EA groups (15 mice/group). The myocardial hypertrophy model was established by subcutaneous injection of isoproterenol hydrochloride (15 mg·kg-1·d-1) for 14 days. The mice of the control group received subcutaneous injection of same amount of normal saline. The mice of the EA group received EA stimulation (frequency of 2 Hz, intensity of 1 mA) of bilateral PC6 for 20 min each time, once a day for 14 consecutive days. After the intervention, the body weight, tibia length and heart weight were measured. The left ventricular ejection fraction (EF), fractional shortening index (FS), left ventricular end-systolic volume (LVEV), left ventricular end-systolic internal diameter (LVID) and left ventricular posterior wall thickness (LVPW) were measured by using echocardiography for evaluating the cardiac function. The mean number and surface area of myocardial cells was detected by wheat germ agglutinin (WGA) staining, and changes of the cardiac morphology were observed under light microscopy after HE staining. The expression levels of TRPC1, TRPC3, TRPC4 and TRPC6 (TRPC1/3/4/6) in the myocardial tissue were detected by real-time quantitative PCR (qPCR) and Western blot, separately.
RESULTS: Compared with the control group, the heart-body weight ratio(P<0.05) and heart-weight-to-tibia-length ratio (P<0.01), LVEV and LVID levels, the relative surface area, left ventricular area ratio, and the expression levels of cardiac TRPC1/3/4/6 were significantly increased (P<0.01, P<0.05), while the EF, FS, LVPW, number of cardiomyocytes, and the left ventricular posterior wall ratio were obviously decreased (P<0.01, P<0.05) in the model group. In comparison with the model group, the heart/body weight ratio, heart-weight-to-tibia-length ratio, LVEV and LVID levels, relative surface area, left ventricular area ratio, and the expression levels of cardiac TRPC1/3/4/6 were significantly decreased (P<0.01, P<0.05), while the EF, FS, LVPW, number of cardiomyocytes and left ventricular posterior wall ratio were significantly increased (P<0.01, P<0.05) in the EA group. H.E. staining showed disordered arrangement of cardiomyocytes and obvious myocardial interstitial inflammatory cell infiltration in the model group, and evident reduction of degree of cardiac fibrosis and interstitial edema in the EA group.
CONCLUSIONS: EA of PC6 can improve the cardiac function and cardiac morphology in mice with myocardial hypertrophy, which may be related to its functions in down-regulating the expression of transient receptor potential channels.
目的: 观察电针“内关”对心肌肥厚小鼠心功能、心脏形态和心肌组织中瞬时受体电位通道（TRPCs）蛋白表达的影响，探讨电针治疗心肌肥厚的作用机制。方法: C57BL/6小鼠随机分为空白组、模型组和电针组，每组15只。皮下注射盐酸异丙肾上腺素（15 mg·kg-1·d-1）制备心肌肥厚模型。电针组电针双侧“内关”，每次20 min，每日1次，连续14 d。测量小鼠体质量、胫骨长度和心脏质量；超声心动图测量小鼠心室射血分数（EF）、短轴缩短指数（FS）、收缩末期左心室容积（LVEV）、收缩末期左心室内径（LVID）和收缩末期左心室后壁厚度（LVPW）以评价心功能；WGA染色法检测小鼠心肌相对细胞个数和相对细胞平均表面积；HE染色法观察心肌细胞形态变化；qPCR及Western blot法检测心肌组织中TRPC1、TRPC3、TRPC4、TRPC6的mRNA和蛋白表达水平。结果: 与空白组比较，模型组小鼠心体比和心胫比均增加（P<0.05，P<0.01），EF、FS、LVPW降低（P<0.01），LVEV、LVID升高（P<0.01），心肌相对细胞个数减少（P<0.05），心肌相对细胞表面积增加（P<0.01），左心室面积比值升高（P<0.05），左心室后壁比值降低（P<0.05），心肌细胞排列紊乱，心肌间质炎性细胞浸润明显，心肌组织TRPC1、TRPC3、TRPC4、TRPC6 mRNA和蛋白表达明显升高（P<0.01）。与模型组相比，电针组小鼠心体比和心胫比均减小（P<0.01），EF、FS、LVPW升高（P<0.01），LVEV、LVID降低（P<0.01），心肌相对细胞个数增加（P<0.05），相对细胞表面积减小（P<0.05），左心室面积比值降低（P<0.05），左心室后壁比值升高（P<0.05），心肌病理损伤程度减轻，心肌组织TRPC1、TRPC3、TRPC4、TRPC6 mRNA和蛋白表达降低（P<0.01，P<0.05）。结论: 电针“内关”能够改善心肌肥厚小鼠的心脏形态和功能，其机制可能与下调TRPCs有关。.

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.

OBJECTIVE: 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.