高血压是引起心衰和心源性猝死的危险因素，但介导心脏功能失调的分子机制尚不清楚。最近报道提出肌丝钙结合程度（肌钙蛋白C与钙结合亲和力与数量）影响细胞内钙平衡和心肌收缩，甚至诱导心律失常。至今，高血压心肌细胞肌丝钙结合程度的临床意义没有研究。课题组前期工作结果表明，调节肌丝钙结合的肌钙蛋白I的磷酸化（TnI-Ser23/24）在高血压大鼠心肌细胞明显降低。另外，肌球蛋白结合蛋白C（myosin binding protein C, cMyBPC）及其磷酸化（cMyBPC-Ser282, cMyBPC-er273和cMyBPC-Ser302）显著增加，提示肌丝钙结合增加。因此，本项目预使用cMyBPC磷酸化基因修饰正常和高血压小鼠模型来研究cMyBPC对心肌细胞肌丝钙结合，细胞内钙和收缩功能调节的影响。揭示高血压心肌细胞钙调节新的机制能提高对心衰和心律失常的认识，具有重要的临床意义。

Hypertension is a critical risk factor for fatal cardiovascular diseases (such as heart failure and sudden cardiac death) but molecular mechanisms mediating cardiac dysfunctions remain unclear. Recent reports suggest that myofilament Ca binding (the affinity and capacity of troponin C binding to Ca) regulates intracellular Ca ([Ca2+]i) homeostasis, contraction and even induces arrhythmias. Until recently, myofilament Ca binding of cardiomyocyte in hypertension and its clinical implication remain unidentified. Preliminary research from our group has indicated that phosphorylation of cardiac troponin I (TnI-Ser23/24) was significantly reduced in hypertensive rat cardiomyocytes. In addition, myosin binding protein C (cMyBPC) phosphorylation (cMyBPC-Ser282, cMyBPC-Ser273, cMyBPC-Ser302) was significantly increased，suggesting increased myofilament Ca binding. Therefore, we propose to use genetically modified cMyBPC phosphorylation mice models in this study to investigate the effects of cMyBPC on myofilament Ca binding, [Ca2+]i handling in cardiomyocytes of hypertensive mice and myocyte contraction。Revealing novel mechanisms of [Ca2+]i handling of cardiomyocytes from hypertension will improve our understandings of the underlying mechanisms of heart failure and cardiac arrhythmias, the study possesses great clinical significance.