Blockade of sarcolemmal TRPV2 accumulation inhibits progression of dilated cardiomyopathy

Abstract

Sarcolemmal TRPV2 accumulation appears to have considerable pathological impact on DCM progression, and blockade of this channel may be a promising therapeutic strategy for treating advanced heart failure.

Transient Receptor Potential Channels as Drug Targets: From the Science of Basic Research to the Art of Medicine

“…As a cautionary note, postischemic cardiac recovery was impaired in the TRPV1-null mice . Finally, TRPV2 was found to be increased in the sarcolemma of patients with dilated cardiomyopathy (Iwata et al, 2013). The TRPV2 inhibitor tranilast slowed down the progression of dilated cardiomyopathy in both hamster (d-sarcoglycandeficient animals) and mouse (transgenic animals overexpressing sialyltransferase) models of the human disease.…”

“…TRPM4 (Guinamard et al, 2006), TRPV1 (Thilo et al, 2010), and TRPV2 (Iwata et al, 2013) may also be involved in the development of cardiac hypertrophy. In spontaneously hypertensive rats, increased levels of TRPM4 were reported (Guinamard et al, 2006).…”

Tranilast: A review of its therapeutic applications

“…The blockade of TRPV2 might explain some of the destructive effects of tranilast on the endocrine pancreas, at least in part, since TRPV2 is required for insulin secretion. Tranilast therapy may also be important in the muscular dystrophy and/or cardiomyopathy, and these conditions have been linked to TRPV2 expression and calcium entry [188,189]. Nevertheless, the association between TRPV2 and the effects of tranilast are still not well understood, therfore further investigations in this area could yield respectable results.…”

Axial stretch-dependent cation entry in dystrophic cardiomyopathy: Involvement of several TRPs channels

“…Indeed, TRPV2 channels seem to be involved in the formation and the maintenance of integrity of the intercalated disks and have a key role in the mechanotransduction in these specific areas of cardiomyocytes [20]. In DMD, TRPV2 channels have been suggested to be involved in the progression of the pathology in both skeletal and cardiac muscle with an abnormal sarcolemmal localization [40,41]. TRPV2 channels were also shown to be enriched at the sarcolemma of DMD human skeletal myotubes and to support an exagerated divalent cation entry in response to THC [44].…”

“…In a pathological context, they have been demonstrated to be involved in the pathogenesis of myocyte degeneration in dystrophic muscle [43] and to support elevated divalent cation entry in human DMD myotubes [44]. Their sarcolemmal accumulation has been shown in dystrophic ventricular cardiomyocytes in several studies [40,41] suggesting a role in Ca 2+ dysregulation that can lead to cardiomyocytes death.…”