The effects of telmisartan on the nuclear factor of activated T lymphocytes signalling pathway in hypertensive patients

Abstract

Hypothesis:Previous studies provide links between the nuclear factor of activated T lymphocytes (NFAT) signalling pathway and the development of hypertension. Our preliminary studies indicate that telmisartan can block Kv1.3 potassium channels and effectively inhibit potassium current densities, along with Kv1.3 mRNA and protein expression levels. This paper aims to investigate whether telmisartan has an inhibitory effect on the NFAT signalling pathway after activation and proliferation of peripheral blood T lymphocytes in Kazakh patients with essential hypertension (EH) from Xinjiang, China.Materials and methods:T lymphocytes were isolated using the immunomagnetic cell sorting method (MACS). The mRNA expression of NFATc1, IL-6 and TNF-α was measured by quantitative polymerase chain reaction (qRT-PCR) and relative protein levels were evaluated by Western blot. T cell samples from 50 hypertensive Kazakh patients from Xinjiang were randomly divided into control, telmisartan, cyclosporin A (CsA), VIVIT, and 4-aminopytidine (4-AP) groups. Peripheral blood T lymphocytes were first activated and proliferated in vitro, then incubated for 48 h under different treatment conditions before determination of protein and mRNA expression of NFATc1, IL-6, and TNF-α by Western blot and qRT-PCR analyses, respectively.Results:There were no significant differences in cardiovascular risk factors among the patients with samples assigned to the five groups (p > 0.05). Expression of NFATc1, IL-6, and TNF-α mRNA and protein was significantly reduced in T lymphocytes in all treatment groups (telmisartan, CsA, VIVIT, and 4-AP) compared with controls.Conclusions:Antihypertensive function and inhibitory effects of telmisartan on the T lymphocyte NFAT signalling pathway are unlikely to affect the normal immune function of hypertensive patients. Telmisartan may exert anti-inflammatory effects by inhibition of the NFAT signalling pathway in the T lymphocytes of hypertensive patients.

Omega-3 mechanism of action in inflammation and endoplasmic reticulum stress in mononuclear cells from overweight non-alcoholic fatty liver disease participants: study protocol for the “Brazilian Omega Study” (BROS)—a randomized controlled trial

“…The sample size calculation was carried out using the G * Power 3.1.9.2 software, and the following values and information were considered: [ 1 ] two groups (control and treatment) and [ 2 ] effect size d = 1.15 considering the variation of TNFα/βactin protein observed in the study by Huang et al (2016) [ 39 ]. In this study, the control group showed 0.45±0.04 (average of arbitrary units ± standard deviation) for TNFα while the telmisartan treated group showed 0.36±0.04 [ 39 ].…”

Vascular Health Triad in Humans With Hypertension—Not the Usual Suspects

“…A growing body of literature suggests that the family of Ca 2+ /calcineurin-sensitive transcriptional factors of nuclear factor from activated T-cells (NFAT) may play an essential role as a molecular switch that initiates dysfunction in both the endothelium (Cockerill et al, 1995;Boss et al, 1998;Armesilla et al, 1999;Bochkov et al, 2002;Gonzalez Bosc et al, 2004;Zetterqvist et al, 2015;Huang et al, 2016) and vascular smooth muscle (Suzuki et al, 2002;Lipskaia et al, 2003;Amberg et al, 2004;Nilsson et al, 2006;Nieves-Cintrón et al, 2007;Orr et al, 2009;Pang and Sun, 2009;Nilsson-Berglund et al, 2010;Berglund et al, 2012;Shiny et al, 2016;Soudani et al, 2016;Govatati et al, 2019). NFATs regulate multiple downstream mechanisms that initiate vascular dysfunction.…”

“…Specifically, NFATs (I) impair endothelial function through NO-dependent mechanisms (Armesilla et al, 1999;Bochkov et al, 2002;Johnson et al, 2003;Norata et al, 2007;Garcia-Vaz et al, 2020;Wang et al, 2020), (II) increase the expression of inflammatory mediators in the arterial wall promoting atherosclerosis (Pierce et al, 1996;Pang and Sun, 2009;Nilsson-Berglund et al, 2010;Berglund et al, 2012;Zetterqvist et al, 2014;Weng et al, 2017), and (III) initiate pathogenic VSM proliferation (Suzuki et al, 2002;Lipskaia et al, 2003;Nilsson et al, 2006;Nieves-Cintrón et al, 2007;Donato et al, 2009;Orr et al, 2009;Pang and Sun, 2009;Nilsson-Berglund et al, 2010;Yan et al, 2015;Shiny et al, 2016;Soudani et al, 2016;Govatati et al, 2019). In preclinical models, inhibition of NFAT has prevented the activation of inflammatory cytokines (Kiani et al, 2000;Zetterqvist et al, 2014;Bretz et al, 2015;Huang et al, 2016), enhanced eNOS expression (Smith et al, 2011), increased NO bioavailability (Friedman et al, 2014;Zetterqvist et al, 2014Zetterqvist et al, , 2015Garcia-Vaz et al, 2020), prevented VSM proliferation (Lipskaia et al, 2003;Berglund et al, 2012;Shiny et al, 2016…”

“…Currently, these investigations/findings are limited to cellular and animal models. There are promising approaches, including examining NFATs in the skin microcirculation and in peripheral blood mononuclear cells, for investigating the role of NFATs in humans (Huang et al, 2016). Elucidation of the role of NFATs and their putative upstream contributions to the vascular health triad in humans is still needed.…”

DNA Methylation in NFATC1 Gene Promoter is Related to Longevity in Chinese Population

“…It was reported that NFATC1 was highly expressed in hypertension, carcinomas, osteoporosis, and other age-associated diseases [15][16][17][18]. It has been shown in an animal study that the hair follicle stem cells of aged mice could maintain cell activity, generate hair and make the hair stay in youth when NFATC1 was inhibited [19].…”