2. Academic Validation
  3. Cannabidiol represses miR-143 to promote cardiomyocyte proliferation and heart regeneration after myocardial infarction

Cannabidiol represses miR-143 to promote cardiomyocyte proliferation and heart regeneration after myocardial infarction

  • Eur J Pharmacol. 2023 Dec 3:176245. doi: 10.1016/j.ejphar.2023.176245.
Zhongyu Ren 1,  Yining Liu 2,  Ao Cai 1,  Yang Yu 2,  Xiuxiu Wang 2,  Lan Lan 1,  Xiaofei Guo 2,  Hong Yan 1,  Xinlu Gao 1,  Hanjing Li 1,  Yanan Tian 1,  Haoyu Ji 1,  Hongyang Chen 1,  FengZhi Ding 3,  Wenya Ma 2,  Ning Wang 4,  Benzhi Cai 5,  Baofeng Yang 6
Affiliations

Affiliations

  • 1 Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, 150081, China.
  • 2 Department of Pharmacy, The Second Affiliated Hospital of Harbin Medical University (Institute of Clinical Pharmacy, The University Key Laboratory of Drug Research, Heilongjiang Higher Education Institutions), Harbin, 150001, China.
  • 3 Department of Physiology, Wannan Medical College, Wuhu, 241000, China.
  • 4 Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, 150081, China. Electronic address: [email protected].
  • 5 Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, 150081, China; Department of Pharmacy, The Second Affiliated Hospital of Harbin Medical University (Institute of Clinical Pharmacy, The University Key Laboratory of Drug Research, Heilongjiang Higher Education Institutions), Harbin, 150001, China. Electronic address: [email protected].
  • 6 Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, 150081, China. Electronic address: [email protected].
PMID: 38052413 DOI: 10.1016/j.ejphar.2023.176245
Abstract

Mammalian heart is capable to regenerate almost completely early after birth through endogenous cardiomyocyte proliferation. However, this regenerative capacity diminishes gradually with growth and is nearly lost in adulthood. Cannabidiol (CBD) is a major component of cannabis and has various biological activities to regulate oxidative stress, fibrosis, inflammation, and cell death. The present study was conducted to investigate the pharmacological effects of CBD on heart regeneration in post-MI mice. MI models in adult mice were constructed via coronary artery ligation, which were administrated with or without CBD. Our results demonstrate that systemic administration (10 mg/kg) of CBD markedly increased cardiac regenerative ability, reduced infarct size, and restored cardiac function in MI mice. Consistently, in vitro study also showed that CBD was able to promote the proliferation of neonatal cardiomyocytes. Mechanistically, the expression of miR-143-3p related to cardiomyocyte proliferation was significantly down-regulated in CBD-treated cardiomyocytes, while the overexpression of miR-143-3p inhibited cardiomyocyte mitosis and eliminated CBD-induced cardiomyocyte proliferation. Moreover, CBD enhanced the expression of YAP and Ctnnd1, which were demonstrated as the target genes of miR-143-3p. Silencing of YAP and Ctnnd1 hindered the proliferative effects of CBD. We further revealed that inhibition of the Cannabinoid Receptor 2 impeded the regulatory effect of CBD on miR-143-3p and its downstream target YAP/Ctnnd1, which ultimately eliminated the pro-proliferative effect of CBD on neonatal and adult cardiomyocytes. Taken together, CBD promotes cardiomyocyte proliferation and heart regeneration after MI via miR-143-3p/YAP/Ctnnd1 signaling pathway, which provides a new strategy for cardiac repair in adult myocardium.

Keywords

Cannabidiol; Cannabinoid receptor 2; Cardiomyocyte proliferation; Heart regeneration; Myocardial infarction; miR-143–3p.

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