Decreased Expression of Transient Receptor Potential Vanilloid 1 Impaires the Postischemic Recovery of Diabetic Mouse Hearts

Abstract

iabetes mellitus (DM) is one of the most important risk factors of cardiovascular diseases, and numerous patients who are afflicted with diabetes usually suffer the diffused stenosis of coronary arteries, leading to dreadful consequences such as myocardial infarction and cardiomyopathy. Non-invasive evaluation tools such as Doppler echocardiography demonstrate the impairment of cardiac function in diabetic animal models as well as in diabetic patients, 1,2 whereas the mechanism is still not well elucidated.Neuropathy is one of the common complications of diabetes, which could result in the degeneration of the nerve fibers both in diabetic animals and patients. 3-5 Transient Receptor Potential Vanilloid 1 (TRPV1) is a non-selective cation channel and is diversely distributed in terminals of sensory nerve fibers, dorsal root ganglia (DRG), spinal cord, and many other various regions in the brain. 6 It could lead to the release of neurotransmitters such as calcitonin generelated peptide (CGRP) from peripheral nerve terminals when activated by capsaicin, protons, noxious heat, etc. 7,8 It has been found that in diabetes-prone NOD mice, the protein expression and function of TRPV1 was significantly depressed in DRG. 9 Using immunohistochemical staining, TRPV1 was also found to be reduced in epineurial arterioles in long-term diabetic rats. 10 These investigations suggest that the expression of TRPV1 is susceptible to diabetes. In addition, recent studies disclose that TRPV1 is expressed in the myocardium and perivascular region, which are close to the epicardial surface of ventricles. 11 We revealed that the expression of TRPV1 in diabetic hearts was significantly suppressed in our previous study. 12 However, the impact of the decreased TRPV1 on the diabetic heart has not been investigated yet.A few studies have revealed that TRPV1 can serve as a molecular integrator of various noxious stimuli, especially the myocardial ischemia, in order to protect the hearts against ischemic injury. 11,13 For example, exogenous agonists of TRPV1 exert a cardioprotective effect on ischemia/reperfusion injury, whereas TRPV1 gene knockout eliminates the protection. 14,15 Therefore, it is reasonable to hypothesize that the alteration of TRPV1 secondary to diabetes can be related to the severe postischemic injury of the heart.In the present study, we measure the expression of TRPV1 and CGRP in diabetic hearts and investigate the effect of TRPV1 on the cardiac function after ischemia injury. The results might help explain the vulnerability of diabetic hearts to ischemic injury.

Calcium signaling in diabetic cardiomyocytes

“…In the case of TRPV1, which is mainly expressed at cardiac sensory neurons and activates nociceptors to detect tissue ischemia [39], its expression has been found diminished in diabetes [40]. In this sense, alteration of TRPV1 may impair post-ischemic recovery of diabetic mouse hearts [46]. Finally, very recent data argue in favor of TRPM2 participation in the protection of hearts against I/R injury via reducing ROS generation and increasing ROS scavenging capability in adult cardiomyocytes, by maintaining normal mitochondrial function [43].…”

Hyperosmolar Dextrose Injection for Recalcitrant Osgood-Schlatter Disease

“…45 Studies on glucose effects on neuropeptides are limited thus far, but there are indications that either dextrose elevations or a related reduction in insulin levels downregulate the activity of the transient receptor potential vanilloid type 1 (TRPV1) receptor which reduces production of pain producing (substance P) and degenerative (calcitonin gene-related peptide [CGRP]) neuropeptides. [46][47][48] …”

Role of the Acid-Sensing Ion Channel 3 in Blood Volume Control

“…7 The other candidate might be TRPV1, which plays a role in neurosensory mechanotransduction involved in cardiovascular homeostasis. 2,28, 29 Although our data support a role for ASIC3 in blood volume control, obtaining direct evidence of the involvement of ASIC3 in sensing the volume receptor stretch is still a challenge. Previous studies have demonstrated that loss of Asic3 in mice alters mechanotransduction in the gastrointestinal tract, skin, and auditory system.…”