REPETITIVE TRANSIENT ISCHEMIA-INDUCED CARDIAC ANGIOGENESIS IS MEDIATED BY CaMKIIi ACTIVATION
Yang-Gan Wang, M.D., Ph.D.
, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, China
Background: Coronary angiogenesis is an important protective mechanism in response to myocardial ischemia in coronary artery disease. However, the underlying mechanism remains largely unclear. Here, we investigated the role of CaMKII activation in ischemia-induced cardiac angiogenesis.
Methods and Results: Repetitive transient ischemia model was established in C57/BL6 mice by daily multiple episodes (3 times/day) of short time (5 min) occlusion of the left anterior descending artery for 7 days. Coronary angiogenesis was detected by CD31 immunofluorescence staining. We found that coronary angiogenesis was induced in the border zone of ischemia and suppressed by the chronic intraperitoneal injection of CaMKII inhibitor KN93. RT-qPCR and Western blot analyses showed that myocardial ischemia induced an increased expression and autophosphorylation of CaMKII. VEGF expression was increased in the ischemia model and blunted by KN93. Moreover, KN93 suppressed the proliferation and migration of cardiac endothelial cells in hypoxic condition, in which the expression of CaMKII, p-CaMKII and VEGF were remarkably increased.
Conclusions: CaMKII activation is an important mediator for the ischemia-induced coronary angiogenesis, in which CaMKII-triggered VEGF expression plays a key role.