Deficiency of Caveolin-1 Aggravates Cardiac Infarction Injury by Disturbing the Endothelial Homeostasis.

Objective

Caveolin-1 (Cav-1) plays a crucial role in maintaining the homeostasis of vascular endothelium. Endothelial dysfunction is involved in many ischemic diseases. However, the role of Cav-1 in myocardial infarction (MI) has not been fully elucidated. Here, this study aims to delineate the function of Cav-1 in MI injury and its impact on endothelial homeostasis.

Methods

To elucidate the role of Cav-1 in MI in vivo, we generated the global knockout Cav-1 (Cav-1-KO) mice. And we manipulated the expression of Cav-1 by siRNA in vitro to evaluate the effects apoptosis, inflammatory response and oxidative stress as well as autophagy flux under the hypoxic model of endothelial cells (ECs).

Results

Initially, we found that Cav-1 was mainly expressed in vascular endothelial cells of myocardium. Interestingly, we found that Cav-1 deficiency significantly amplified the size of myocardial infarction areas, alongside the deteriorated cardiac function in vivo. Consistently in vitro, siRNA-mediated knockdown of Cav-1 exacerbated the endothelial apoptosis, inflammatory response and oxidative stress as well as eliminated autophagy flux. However, pretreatment with β-cyclodextrin (β-CD), which depletes membrane-bound cholesterol and disrupts lipid rafts, markedly mitigated the effects induced by downregulation of Cav-1, respectively.

Conclusion

Collectively, in this study, we demonstrated that Cav-1 acts as a protective regulator of MI injury through maintaining endothelial homeostasis. These findings implied that Cav-1 may be a potential therapeutic target for MI injury.