Int J Biol Sci 2020; 16(2):298-308. doi:10.7150/ijbs.35075 This issue Cite

Research Paper

25-Hydroxycholesterol protects against myocardial ischemia-reperfusion injury via inhibiting PARP activity

Suying Lv1,2,*, Chenhui Ju1,2,*, Jiangtong Peng1,2,*, Minglu Liang1,2, Feng Zhu1,2, Cheng Wang1,3, Kai Huang1,2, Min Cheng1,2✉, Fengxiao Zhang1,2✉

1. Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
2. Clinic Center of Human Gene Research, Union Hospital, Tongji Medical College, Huazhong, University of Science and Technology, Wuhan, China
3. Department of Rheumatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
*Suying Lv, Chenhui Ju and Jiangtong Peng contributed equally as co-first authors

Citation:
Lv S, Ju C, Peng J, Liang M, Zhu F, Wang C, Huang K, Cheng M, Zhang F. 25-Hydroxycholesterol protects against myocardial ischemia-reperfusion injury via inhibiting PARP activity. Int J Biol Sci 2020; 16(2):298-308. doi:10.7150/ijbs.35075. https://www.ijbs.com/v16p0298.htm
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Abstract

Graphic abstract

Myocardial ischemia-reperfusion (IR) injury occurs when occlusive coronary artery restores blood supply after events such as myocardial infarction, stroke, cardiac arrest and resuscitation, and organ transplantation. However, the mechanisms involved are poorly understood, and effective pharmacological interventions are still lacking. A previous study demonstrated that 25-hydroxycholesterol (25-HC) contributed to lipid metabolism and cholesterol metabolism as an oxysterol molecule. We herein explored whether 25-hydroxycholesterol (25-HC) has cardioprotective properties against IR injury and explored its underlying mechanisms. 25-HC was administered before reperfusion procedure in IR injury model mice. We found that 25-HC significantly reduced the IR-induced infarct size and improved cardiac function, and this protective effect was associated with reduced phosphorylation of p38-MAPK and JNK1/2. Besides, 25-HC also inhibited the Bax/Bcl-2 ratio and the relative expression of cleaved caspase-3. Furthermore, 25-HC decreased the PARP activity, indicating that 25-HC ameliorates IR injury via the PARP pathway. The 25-HC group abolished cardioprotection in the presence of little PARP activity, suggesting that the PARP activity is essential for 25-HC to exert its effect during IR injury. Our primary study indicates that 25-HC ameliorated IR injury by inhibiting the PARP activity and decreasing myocardial apoptosis, which makes it a potential therapeutic drug in IR injury of the heart.

Keywords: myocardial ischemia-reperfusion, myocardial apoptosis, 25-hydroxycholesterol, PARP


Citation styles

APA
Lv, S., Ju, C., Peng, J., Liang, M., Zhu, F., Wang, C., Huang, K., Cheng, M., Zhang, F. (2020). 25-Hydroxycholesterol protects against myocardial ischemia-reperfusion injury via inhibiting PARP activity. International Journal of Biological Sciences, 16(2), 298-308. https://doi.org/10.7150/ijbs.35075.

ACS
Lv, S.; Ju, C.; Peng, J.; Liang, M.; Zhu, F.; Wang, C.; Huang, K.; Cheng, M.; Zhang, F. 25-Hydroxycholesterol protects against myocardial ischemia-reperfusion injury via inhibiting PARP activity. Int. J. Biol. Sci. 2020, 16 (2), 298-308. DOI: 10.7150/ijbs.35075.

NLM
Lv S, Ju C, Peng J, Liang M, Zhu F, Wang C, Huang K, Cheng M, Zhang F. 25-Hydroxycholesterol protects against myocardial ischemia-reperfusion injury via inhibiting PARP activity. Int J Biol Sci 2020; 16(2):298-308. doi:10.7150/ijbs.35075. https://www.ijbs.com/v16p0298.htm

CSE
Lv S, Ju C, Peng J, Liang M, Zhu F, Wang C, Huang K, Cheng M, Zhang F. 2020. 25-Hydroxycholesterol protects against myocardial ischemia-reperfusion injury via inhibiting PARP activity. Int J Biol Sci. 16(2):298-308.

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