Study Of Calcium Silicate Inhibition Of Cardiac Hypertrophy And Cardiac Fibrosis

The main function of the heart is to pump the blood to various organs in the body.Pathological cardiac hypertrophy and fibrosis will be induced within a long time pathological stress and it is one of the main activating factors of heart failure.Currently,there is no effective drug that can completely reverse or inhibit the development of pathological cardiac hypertrophy and fibrosis.To this end,we propose a novel method for treating cardiac hypertrophy and cardiac fibrosis with silicate ions based on calcium silicate（CS）bioceramic extract and calcium silicate electrospun membrane.This study confirmed the therapeutic effects of calcium silicate bioceramics on cardiac hypertrophy and cardiac fibrosis from in vitro and in vivo experiments.For in vitro experiments,angiotensin Ⅱ（Ang Ⅱ）-induced cardiomyocyte hypertrophy model and neonatal rat myocardial fibroblast fibrosis model were constructed,and then the calcium silicate extract or calcium silicate electrospun membrane were used to explore the effects of calcium silicate on cardiomyocyte hypertrophy and fibroblast fibrosis.For in vivo experiments,an Ang Ⅱ-induced myocardial hypertrophy model in mice was constructed,and silicate ion was injected intravenously.In addition,we also constructed another myocardial hypertrophy and cardiac fibrosis models using transverse aortic constriction（TAC）,and the prepared electrospun membrane were pasted on the surface of the heart randomly to explore the effects of calcium silicate on cardiomyocyte hypertrophy and cardiac fibrosis in mice.The in vitro results showed that calcium silicate extract could inhibit Ang Ⅱ-induced cardiomyocyte hypertrophy（cell surface area increased from 1266μm² to 2691μm² and decreased to 1637μm²）,including reduction the levels of cardiac hypertrophy-related genes atrial natriuretic peptide（ANP）,brain natriuretic peptide（BNP）andβ-myosin heavy chain（β-MHC）m RNA expression.Further analysis revealed that silicate ion could inhibit cardiomyocyte hypertrophy by regulating intracellular Ca²⁺homeostasis.At the same time,we also found that calcium silicate extract could inhibit the fibrosis of cardiac fibroblasts induced by Ang Ⅱ,and reduce the m RNA expression levels of cardiac fibrosis-related genes includingα-smooth muscle actin（α-SMA）and collagen type Ⅰ（Collagen Ⅰ）.In addition,4%CS-PLLA could inhibit the hypertrophy of cardiomyocytes induced by Ang Ⅱ significantly（cell surface area increased from 226μm² to 437μm² and decreased to 237μm²）.The in vivo results showed that injection of silicate extract intravenously could significantly decrease the ratio of heart weight to body weight the cardiomyocyte size in the heart tissue,and reduce the mRNA expression levels of cardiac hypertrophy-related genes including ANP,BNP,andβ-MHC,promote the angiogenesis-related genes including vascular endothelial growth factor（VEGF）,basic fibroblast growth factor（bFGF）,and vascular endothelial growth factor receptor 2（KDR）,thereby further promoting the formation of capillaries and reducing Ang Ⅱ induced cardiac dysfunction.Moreover,4%CS-PLLA could inhibit TAC-induced enlargement of cardiomyocytes and collagen deposition near the vascular and cardiac interstitial to some extent in mouse heart tissue.Therefore,calcium silicate have potential value as a new therapeutic strategy for the treatment of pathological cardiac hypertrophy and fibrosis,and this finding provide new insights into the clinical treatment of cardiac hypertrophy and fibrosis.