Transient receptor potential vanilloid type 1: cardioprotective effects in diabetic models

Abstract

Cardiovascular disease, especially heart failure (HF) is the leading cause of death in patients with diabetes. Individuals with diabetes are prone to a special type of cardiomyopathy called diabetic cardiomyopathy (DCM), which cannot be explained by heart diseases such as hypertension or coronary artery disease, and can contribute to HF. Unfortunately, the current treatment strategy for diabetes-related cardiovascular complications is mainly to control blood glucose levels; nonetheless, the improvement of cardiac structure and function is not ideal. The transient receptor potential cation channel subfamily V member 1 (TRPV1), a nonselective cation channel, has been shown to be universally expressed in the cardiovascular system. Increasing evidence has shown that the activation of TRPV1 channel has a potential protective influence on the cardiovascular system. Numerous studies show that activating TRPV1 channels can improve the occurrence and progression of diabetes-related complications, including cardiomyopathy; however, the specific mechanisms and effects are unclear. In this review, we summarize that TRPV1 channel activation plays a protective role in the heart of diabetic models from oxidation/nitrification stress, mitochondrial function, endothelial function, inflammation, and cardiac energy metabolism to inhibit the occurrence and progression of DCM. Therefore, TRPV1 may become a latent target for the prevention and treatment of diabetes-induced cardiovascular complications.

Keywords: Transient receptor potential vanilloid type 1; cardiovascular complication; diabetes; endothelial function; inflammation; oxidative stress.

Figure 1.

Basic mechanism of diabetes cardiomyopathy. Systemic hyperglycemia, insulin resistance, and deposition of advanced glycation end products (AGEs) caused by diabetes can induce cardiac metabolic changes, promote myocyte inflammation, endothelial cell damage, and mitochondrial dysfunction. These pathways interact with each other, directly or indirectly leading to cardiac hypertrophy, fibrosis, and ischemia, ultimately leading to dysfunction of cardiac relaxation and contraction.

Figure 2.

Schematic diagram of CGRP and SP release caused by TRPV1 activation. Substance P and CGRP-positive dorsal root ganglia (DRG) neurons often co-express transient receptor potential vanilloid (TRPV1) channel. When TRPV1 is activated, the conformation of TRPV1 changes, the channel opens, the permeability to cations (mainly Ca2+) increases, 1) the influx of cations such as Ca2+ produces depolarizing action potential;2) CGRP is packaged and co-released with substance P in a calcium dependent manner due to depolarization or increased intracellular calcium.