ISSN 2149-2263 | E-ISSN 2149-2271
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Renal Denervation Ameliorates Cardiomyocyte Apoptosis in Myocardial Ischemia–Reperfusion Injury Through Regulating Mitochondria–Endoplasmic Reticulum Contact [Anatol J Cardiol]
Anatol J Cardiol. 2024; 28(7): 353-362 | DOI: 10.14744/AnatolJCardiol.2024.3579

Renal Denervation Ameliorates Cardiomyocyte Apoptosis in Myocardial Ischemia–Reperfusion Injury Through Regulating Mitochondria–Endoplasmic Reticulum Contact

Zheng Zhao1, Faquan Li2, Yiyao Jiang3, Chengzhi Lu2
1The First Central Clinical School, Tianjin Medical University, Tianjin, China; Department of Cardiology, Cangzhou Central Hospital, Hebei, China
2The First Central Clinical School, Tianjin Medical University, Tianjin, China
3Department of Cardiovascular Surgery, the First Affiliated Hospital of Bengbu Medical College, Anhui, China

Background: Myocardial ischemia–reperfusion injury (I/R) has been improved with drugs and effective reperfusion, but it still cannot be prevented.

Methods: To investigate whether renal denervation (RDN) reduces cardiomyocyte apoptosis by ameliorating endoplasmic reticulum stress, 60 male specific pathogen-free (SPF) Wistar rats were randomly divided into 6 groups (n = 6). We established the I/R rat model by ligating the left anterior descending artery. The I/R+ angiotensin receptor neprilysin inhibitors (ARNI) group received ARNIs for 2 weeks until euthanasia.

Results: The I/R+RDN and I/R+ARNI groups have significantly ameliorated left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) and reversed expansion of the left ventricular end-systolic diameter (LVSD) and left ventricular end diastolic diameter (LVDD) compared to the I/R group. The levels of norepinephrine (NE), angiotensin II, and aldosterone (ALD) increased significantly in the I/R group, but decreased significantly after RDN and ARNI intervention. In the I/R+RDN and I/R+ARNI groups, the myocardial tissue edema was alleviated. The infarct size was smaller in the I/R+RDN and I/R+ARNI groups compared to the I/R group. Apoptosis of cardiomyocytes and fibroblasts in myocardial tissue increased significantly in the I/R group, which was greatly diminished by RDN and ARNI. The expression of Bax, caspase-3, CHOP, PERK, and ATF4 protein was significantly increased in the I/R group, which compared to other groups, and the level of CHOP, PERK, and ATF4 gene expression increased. After RDN intervention, these expression levels recovered to varying degrees.

Conclusion: The effect of RDN may be associated with regulating the endoplasmic reticulum stress PERK/ATF4 signaling pathway.

Keywords: Myocardial ischemia–reperfusion injury, renal denervation, ARNI, endoplas-mic reticulum stress, cardiomyocyte apoptosis

Zheng Zhao, Faquan Li, Yiyao Jiang, Chengzhi Lu. Renal Denervation Ameliorates Cardiomyocyte Apoptosis in Myocardial Ischemia–Reperfusion Injury Through Regulating Mitochondria–Endoplasmic Reticulum Contact. Anatol J Cardiol. 2024; 28(7): 353-362

Corresponding Author: Zheng Zhao
Manuscript Language: English


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