Caveolin-1 alleviates angiotensin Ⅱ induced endothelial injury and cerebral microbleed via mitochondrial protection

Abstract Cerebral microbleeds are a manifestation of cerebral small vessel disease (CSVD) and a predictor of cerebral hemorrhage. However, the causes of cerebral microbleeds remain unclear. Research on the mechanism of cerebral microbleeds may provide new ideas for the treatment of CSVD. In a mouse model, we show cerebral microbleeds and cognitive impairment with increasing expression of caveolin-1 (Cav-1). Mechanistically, in an in vitro study, we find that Cav-1 knockdown significantly affects the mitochondrial pathway in the cytoplasm and decreases the endothelial viability. Moreover, Cav-1 knockdown induces mitochondrial membrane potential (MMP) depolarization and mitochondria reactive oxygen species (ROS) production. By contrast, overexpression of Cav-1 alleviates the decrease of cell viability, MMP depolarization and mitochondria ROS production induced by angiotensin Ⅱ (Ang Ⅱ). Furthermore, Cav-1 activation significantly improves cerebral microbleeds and cognitive impairment in CSVD mice. We identify Cav-1 as an endogenous protective molecule via mitochondrial protection, and activation of Cav-1 resists microbleeds and cognitive impairment in an animal model of CSVD. Cav-1 might be a candidate therapeutic target for CSVD.