Huoxue Wentong Formula ameliorates myocardial infarction in rats through inhibiting CaMKII oxidation and phosphorylation
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Chinese Medicine Open Access
RESEARCH
Huoxue Wentong Formula ameliorates myocardial infarction in rats through inhibiting CaMKII oxidation and phosphorylation Tiantian Liu, Qingqing Wang and Kuiwu Yao*
Abstract Background: The Chinese medicine Huoxue Wentong Formula (HXWTF) was used to treat thoracic obstruction and angina pectoris in clinic, which has not been investigated in myocardial ischemia-induced apoptosis and angiogenic function. Here we aimed to investigate the roles of HXWTF in rats with myocardial ischemia-induced apoptosis and angiogenesis disorders, as well as to reveal the potential mechanisms. Methods: Male SD rats were subjected to coronary artery ligation followed by HXWTF (420, 840 and 1680 mg/kg/ day, p.o.) or isosorbide mononitrate (6.3 mg/kg/day, p.o.) treatment for 4 weeks. Electrocardiogram (ECG) and Echocardiography (ECHO) were used to measure cardiac function. Hematoxylin and eosin (H&E) staining and CD34/α-SMA immunohistochemical staining were performed to observe the ischemic heart sections pathological changes and angiogenesis. Then, the effects on cardiomyocyte apoptosis of H9c2 and tube formation of HCMECs were observed, as well as the changes in the levels of total calmodulin dependent protein kinase II (t-CaMKII), phosphorylated CaMKII (p-CaMKII), oxidized CaMKII (ox-CaMKII), CD34, and Bcl-2/Bax ratio were detected. Results: Rats with coronary artery ligation exhibited abnormal cardiac function, enlarged myocardial space, disorderly arranged myocardial fibers, inflammatory cells infiltrated, and aggravated myocardial cell apoptosis, along with angiogenesis dysfunction. The expressions of CD34, p-CaMKII, and ox-CaMKII were elevated and Bcl-2/Bax ratio was diminished in ischemic hearts and H/SD-treated H9c2 or HCMECs, while HXWTF treatment completely rescued angiogenic dysfunction, inhibited cardiomyocyte apoptosis, and down-regulated cardiac CaMKII oxidation and phosphorylation activities. Conclusion: Our study demonstrates that HXWTF improves myocardial infarction possibly through inhibiting CaMKII oxidation and phosphorylation levels, facilitating angiogenic function and alleviating cardiomyocyte apoptosis. Thus, therapeutics targeting CaMKII activities may be a promising strategy for rescuing ischemic cardiomyopathy. Keywords: HXWTF, CaMKII, Myocardial infarction, Angiogenesis, Apoptosis Background Myocardial infarction (MI) is a serious threat to human life and health, and its morbidity and mortality have ranked first among all kinds of cardiovascular diseases. *Correspondence: [email protected] Department of Cardiology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, No. 5 Beixian’ge, District of Xi Cheng, Beijing 100053, China
MI is a syndrome of myocardial cell necrosis, which is caused by severe and persistent ischemia and hypoxia of the local myocardium induced by coronary artery occlusion [1, 2]. It is well known that myocardial ischemia exacerbates the pathological damage of MI through impairing ischemic vascular remodeling and collateral formation
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