TRPM7 is down‐regulated in both left atria and left ventricle of ischaemic cardiomyopathy patients and highly related to changes in ventricular function

Abstract

AimsThe kinase ion channel transient receptor potential melastatin 7 (TRPM7) is considered a modulator of cardiac fibrosis progression; nevertheless, we lack of studies analysing its role in human ischaemic cardiomyopathy (ICM). Our objective was to analyse the expression of genes encoding cardiac ion channels in human ICM, focusing on the alterations in mRNA levels of TRPM7 and its relationship with changes in the ventricular function.Methods and resultsRNA‐sequencing was carried out in 13 left ventricular (LV) samples of patients with ICM compared with a control group (n = 10). The analysis revealed a total of 25 ion channel genes differentially expressed. We performed an RTqPCR analysis of the TRPM7 mRNA in LV and left atrial samples and found that it was down‐regulated in both cavities (−1.43‐fold and −1.52‐fold, respectively). Atrial TRPM7 mRNA levels showed an excellent and inverse relationships with the depressed ejection fraction (r = −0.724, P = 0.042) and with the mitral A wave (r = −0.938, P = 0.006).ConclusionsWe report the down‐regulation of TRPM7 in tissue samples from both left atria and left ventricle in patients with ICM. We found an inverse relationship between both cardiac chambers mRNA levels with LV dysfunction, suggesting an important role of TRPM7 in the left atrial and LV functional depression found in this cardiomyopathy.

Enhancer and promoter usage in the normal and failed human heart

“…40,54 In ischemic cardiomyopathy, TRPM7 was significantly down regulated in the left atria and ventricle. 39 However, in non-ischemic dilated cardiomyopathy, TRPM7 was shown to be upregulated in patients with ventricular tachycardia. 55 We found a larger magnitude reduction in enhancer eRNA levels compared to reduction in mRNA levels, and this may indicate that additional TRPM7 enhancer regions are active.…”

“…Figure 6D illustrates alternative enhancer use within the first intron of TRPM7, which encodes the transient receptor potential cation channel subfamily M member, a gene implicated in ischemic cardiomyopathy and cardiac rhythm. 39,40 This intronic enhancer showed significantly lower eRNA expression in heart failure ( Figure 6E), concomitant with a significantly lower expression of TRPM7 in failed hearts ( Figure 6F).…”

TRPM7 residue S1269 mediates cAMP dependence of Ca2+ influx

“…Up-and downregulation of mRNA levels in TRPM7-dependent malignancies is also typically very modest [44], implicating tight regulation of TRPM7 levels. Consequently, in our study most tetramers of mutant channels can be expected to contain one or more wt TRPM7 proteins which complicates phenotypic characterization.…”

Salvianolic acid B protects against acute lung injury by decreasing TRPM6 and TRPM7 expressions in a rat model of sepsis

“…These ion channels are unique divalent cation channels that are constitutively opened, as well as exhibiting permeability to Mg2+ and Ca2+ . In recent years, increasing displays of evidences have highlighted TRPM6 and TRPM7 channel kinase's as being vital regulators, capable of modulating a variety of physical developments in disease proceedings such as cytoskeleton organization, cell viability, cardiac fibrosis, and magnesium homeostasis . Liu et al reported that Sal B could inhibit mitogen‐activated protein kinase activity.…”

“…15 In recent years, increasing displays of evidences have highlighted TRPM6 and TRPM7 channel kinase's as being vital regulators, capable of modulating a variety of physical developments in disease proceedings such as cytoskeleton organization, cell viability, cardiac fibrosis, and magnesium homeostasis. 16,17 Liu et al 18 reported that Sal B could inhibit mitogen-activated protein kinase activity. Prior analysis into Sal B pretreatment has revealed that it largely contributes to the treatment of LPS exposure by improving pulmonary injury and pulmonary microcirculation disturbance.…”