Abstract

Transient receptor potential (TRP) superfamily consists of a diverse group of non-selective cation channels that has a wide tissue distribution and is involved in many physiological processes including sensory perception, secretion of hormones, vasoconstriction/vasorelaxation, and cell cycle modulation. In the blood vessels, TRP channels are present in endothelial cells, vascular smooth muscle cells, perivascular adipose tissue (PVAT) and perivascular sensory nerves, and these channels have been implicated in the regulation of vascular tone, vascular cell proliferation, vascular wall permeability and angiogenesis. Additionally, dysfunction of TRP channels is associated with cardiometabolic diseases, such as diabetes and obesity. Unfortunately, the prevalence of diabetes and obesity is rising worldwide, becoming an important public health problems. These conditions have been associated, highlighting that obesity is a risk factor for type 2 diabetes. As well, both cardiometabolic diseases have been linked to a common disorder, vascular dysfunction. In this review, we briefly consider general aspects of TRP channels, and we focus the attention on TRPC (canonical or classical), TRPV (vanilloid), TRPM (melastatin), and TRPML (mucolipin), which were shown to be involved in vascular alterations of diabetes and obesity or are potentially linked to vascular dysfunction. Therefore, elucidation of the functional and molecular mechanisms underlying the role of TRP channels in vascular dysfunction in diabetes and obesity is important for the prevention of vascular complications and end-organ damage, providing a further therapeutic target in the treatment of these metabolic diseases.

Highlights

  • Diabetes mellitus and obesity are characterized by systemic biochemical and biological abnormalities, including metabolic disturbances, increased oxidative stress (Pandey et al, 2010; Fülöp et al, 2014; D’souza et al, 2016), and elevated circulating levels of inflammatory markers (Panagiotakos et al, 2005; Taha et al, 2019)

  • transient receptor potential (TRP) superfamily consists of a diverse group of non-selective cation channels that is divided into six subfamilies in mammals, which are classified as: canonical or classical (TRPC), vanilloid (TRPV), melastatin (TRPM), ankyrin (TRPA), mucolipin (TRPML), and polycystin (TRPP) (Montell, 2005; Ramsey et al, 2006)

  • A recent report demonstrated that diet-induced obesity is associated with impaired Ca2+ influx through TRPV4 channels and vasodilation induced by muscarinic stimulation and GSK1016970A (TRPV4 agonist) in resistance mesenteric arteries from mice

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Summary

Introduction

Diabetes mellitus and obesity are characterized by systemic biochemical and biological abnormalities, including metabolic disturbances, increased oxidative stress (Pandey et al, 2010; Fülöp et al, 2014; D’souza et al, 2016), and elevated circulating levels of inflammatory markers (Panagiotakos et al, 2005; Taha et al, 2019). The authors demonstrated a reduction in the capsaicin-evoked release of CGRP and decrease in the density of perivascular and stromal TRPV1-immunoreactive nerve fibers of the dura mater from diabetic rats, suggesting that insufficient vasodilator function of meningeal sensory nerves may contribute to the higher incidence of headaches in diabetics due to perturbation of tissue homeostasis that could induce additional activation and/or sensitization of meningeal nociceptors (Dux et al, 2007).

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