Abstract
Cardiac microvascular ischemia-reperfusion (IR) injury has been a neglected topic in recent decades. In the current study, we investigated the mechanism underlying microvascular IR injury, with a focus on mitochondrial homeostasis. We also explored the protective role of tanshinone IIA (Tan IIA) in microvascular protection in the context of IR injury. Through animal studies and cell experiments, we demonstrated that IR injury mediated microvascular wall destruction, lumen stenosis, perfusion defects, and cardiac microvascular endothelial cell (CMEC) apoptosis via inducing mitochondrial damage. In contrast, Tan IIA administration had the ability to sustain CMEC viability and microvascular homeostasis, finally attenuating microvascular IR injury. Function studies have confirmed that the SIRT1/PGC1α pathway is responsible for the microvascular protection from the Tan IIA treatment. SIRT1 activation by Tan IIA sustained the mitochondrial potential, alleviated the mitochondrial pro-apoptotic factor leakage, reduced the mPTP opening, and blocked mitochondrial apoptosis, providing a survival advantage for CMECs and preserving microvascular structure and function. By comparison, inhibiting SIRT1 abrogated the beneficial effects of Tan IIA on mitochondrial function, CMEC survival, and microvascular homeostasis. Collectively, this study indicated that Tan IIA should be considered a microvascular-protective drug that alleviates acute cardiac microcirculation IR injury via activating the SIRT1/PGC1α pathway and thereby blocking mitochondrial damage.
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This study was supported by the Natural Science Foundation of Guangdong Province of China (NO: 2018A030313067) , Science and Technology Innovation Project from Foshan, Guangdong (FS0AA-KJ218-1301-0006;FS0AA-KJ218-1301-0010), Key Specialist Department Training Project of Foshan City, Guangdong Province of China ( NO: FSPY3-2015034).
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Zhong, J., Ouyang, H., Sun, M. et al. Tanshinone IIA attenuates cardiac microvascular ischemia-reperfusion injury via regulating the SIRT1-PGC1α-mitochondrial apoptosis pathway. Cell Stress and Chaperones 24, 991–1003 (2019). https://doi.org/10.1007/s12192-019-01027-6
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DOI: https://doi.org/10.1007/s12192-019-01027-6