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World J Diabetes. May 15, 2022; 13(5): 387-407
Published online May 15, 2022. doi: 10.4239/wjd.v13.i5.387
Role of cannabinoids and the endocannabinoid system in modulation of diabetic cardiomyopathy
Mona F El-Azab, Ahmed E Wakiel, Yossef K Nafea, Mahmoud E Youssef
Mona F El-Azab, Ahmed E Wakiel, Department of Pharmacology and Toxicology, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt
Yossef K Nafea, Program of Biochemistry, McMaster University, Hamilton L8S 4L8, Ontario, Canada
Mahmoud E Youssef, Department of Pharmacology and Biochemistry, Delta University for Science and Technology, Mansoura 35511, New Cairo, Egypt
Author contributions: El-Azab MF was responsible for conceptualization and supervision; El-Azab MF and Wakiel AE were responsible for original draft preparation; El-Azab MF, Nafea YK and Youssef ME were responsible for review of the literature and visualization; all authors contributed to the final draft of the manuscript, have read and agreed to the published version of the manuscript.
Conflict-of-interest statement: Authors declare no conflict of interests for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Mona F El-Azab, PhD, Professor, Department of Pharmacology and Toxicology, Faculty of Pharmacy, Suez Canal University, Kilo 4.5 Ring Road, Ismailia 41522, Egypt. mona_elazab@pharm.suez.edu.eg
Received: May 31, 2021
Peer-review started: May 31, 2021
First decision: July 3, 2021
Revised: July 18, 2021
Accepted: April 28, 2022
Article in press: April 28, 2022
Published online: May 15, 2022
Abstract

Diabetic complications, chiefly seen in long-term situations, are persistently deleterious to a large extent, requiring multi-factorial risk reduction strategies beyond glycemic control. Diabetic cardiomyopathy is one of the most common deleterious diabetic complications, being the leading cause of mortality among diabetic patients. The mechanisms of diabetic cardiomyopathy are multi-factorial, involving increased oxidative stress, accumulation of advanced glycation end products (AGEs), activation of various pro-inflammatory and cell death signaling pathways, and changes in the composition of extracellular matrix with enhanced cardiac fibrosis. The novel lipid signaling system, the endocannabinoid system, has been implicated in the pathogenesis of diabetes and its complications through its two main receptors: Cannabinoid receptor type 1 and cannabinoid receptor type 2, alongside other components. However, the role of the endocannabinoid system in diabetic cardiomyopathy has not been fully investigated. This review aims to elucidate the possible mechanisms through which cannabinoids and the endocannabinoid system could interact with the pathogenesis and the development of diabetic cardiomyopathy. These mechanisms include oxidative/ nitrative stress, inflammation, accumulation of AGEs, cardiac remodeling, and autophagy. A better understanding of the role of cannabinoids and the endocannabinoid system in diabetic cardiomyopathy may provide novel strategies to manipulate such a serious diabetic complication.

Keywords: Δ9-tetrahydrocannabinol, Autophagy, Cannabinoid receptors, Diabetic cardiomyopathy, Endocannabinoid system, Inflammation

Core Tip: Diabetic cardiomyopathy is considered to be one of the most common deleterious diabetic complications being the leading cause of mortality among diabetic patients. The endocannabinoid system has been implicated in the pathogenesis of diabetes and its complications. However, the role of the endocannabinoid system in diabetic cardiomyopathy has not been fully investigated. This review aims to elucidate the possible mechanisms through which cannabinoids and the endocannabinoid system could interact with the pathogenesis of diabetic cardiomyopathy. Better understanding of the role of cannabinoids and the endocannabinoid system in diabetic cardiomyopathy may provide novel strategies to manipulate this serious diabetic complication.