NLRP3 Inflammasomes Show High Expression In Xinjiang Kazakh Patients With Hypertension And The Intervention Of Telmisartan

Objective:To study the expression of NLRP3 inflammasome signaling pathway molecules in peripheral blood T lymphocytes of Kazakh patients with essential hypertension (EH), and also explore the possible molecular mechanisms of which this pathway was involved in hypertension pathogenesis.Methods:30 untreated Kazakh hypertensive patients (mean age 54.7 ±5.6 years) and 30 Kazakh healthy subjects (mean age 54.6 ±4.7 years) were randomly collected from June 2013 to February 2014 in Heart Center of the First Affiliated Hospital in Xinjiang. The male to female ratio was 1:1 in each group. The plasma and peripheral blood T lymphocytes were separated. Enzyme linked immunosorbent assay (ELISA) was performed to measure the plasma level of interleukin (IL)-1β. The real time quantitative RT-PCR (qRT-PCR) and western blot analysis were used to detect the mRNA and protein expression levels of NLRP3 inflammasome and its downstream signaling pathway-related molecules, respectively. T lymphocytes of hypertension group were then cultured and proliferated in vitro for 48 hours. Samples of all hypertensive patients were randomly divided into three sections (10 cases in each section) with different treatments, named control group (with PBS treatment), telmisartan group (with telmisartan treatment) and positive control group (with treatment of potassium channel blocker 4-AP). The drug intervention was continued for another 48 hours. Cell cultural supernatants and T lymphocytes of each section were collected before and after drug intervention, respectively. IL-1β level in cell cultural supernatants was detected by ELISA assay, and qRT-PCR and western blot were again used to measure the mRNA and protein relative expression of NLRP3, Caspase-1 and IL-1β in the T lymphocytes.Results:No significance of general condition between the hypertensive group and healthy group was observed. Compared to the healthy controls, an elevated plasma level of IL-ip in patients with EH in Xinjiang Kazakh was shown as evidenced by ELISA assay. Meanwhile, both the mRNA and protein expressions of NLRP3, Caspase-1 and IL-ip were also found to be increased in hypertensive patients. However, after intervention of either potassium channel blocker 4-AP or telmisartan, the IL-1β level in cell cultural supernatant were significantly reduced, the mRNA and protein expressions of NLRP3, Caspase-1 and IL-1β in T lymphocytes were decreased, whereas the treatment with PBS led to no significantly change of IL-1β or NLRP3 inflammasome signaling pathway-related molecules.Conclusions:NLRP3 inflammasome signaling pathway in peripheral blood T lymphocytes of Kazakh patients with EH was inflammatory activated, and the activation of this pathway may be involved in T lymphocytes Kv1.3 potassium channel-triggered hypertension pathogenesis.