Bestrophin 3 参与高血压血管重构及机制研究

我们最近的研究否定了bestrophin 3是钙激活氯通道分子基础的传统观点，但其在心血管系统中的功能不清楚。预实验结果发现，bestrophin 3表达在高血压血管重构过程中显著升高。下调bestrophin 3可抑制血管平滑肌细胞增殖，促进细胞凋亡。Bestrophin 3可直接结合PI3K p110亚基,下调bestrophin 3抑制PI3K-Akt的活化。本研究拟在上述工作基础上，阐明bestrophin 3结合PI3K p110亚基进而调控PI3K-Akt信号及细胞增殖和凋亡的机制，并通过在体实验检测bestrophin 3敲除对高血压血管重构的影响。该工作将从细胞增殖和凋亡角度阐明bestrophin 3的新功能，提出bestrophin 3可能是调控PI3K-Akt信号通路关键分子的新观点，并为评估bestrophin 3是否可作为防治高血压血管重构新靶点提供实验室依据

Our recent study excluded the possibility that bestrophin 3 is the molecular candidate of calcium activated chloride channel,however, its functions in cardiovascular system remain elusive. Our primary data showed that bestrophin 3 expression was increased during hypertension-induced vascular remodeling. Knockdown of bestrophin 3 inhibited cell proliferation but promoted cell apoptosis, in vascular smooth mucle cells. Bestrophin 3 can bind to the PI3K p110 subunit and knockdown of bestrophin 3 reduced the activity of PI3K-Akt pathway. Our present study aimed to further clarify the interaction of bestrophin 3 and PI3K p110 and how this interaction interferes with the activity of PI3K-Akt signaling pathway and thus regulates cell proliferation and apoptosis. Moreover, we will investigate the functional role of bestrophin 3 in regulating hypertension-induced coronary atery remodeling in bestrophin 3 knockout mice. This work will reveal the new functions of bestrophin-3 and raise the possibility that bestrophin 3 is a key regulator of PI3K-Akt pathway,suggesting that bestrophin 3 may be a novel therapeutic target for hypertension-induced vascular remodeling.