Effect of profilin‐1 on the asymmetric dimethylarginine‐induced vascular lesion‐associated hypertension

Abstract

Previous studies have demonstrated that the levels of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide (NO) synthesis, are strongly associated with hypertension, diabetes, and cardiovascular diseases. Profilin‐1, an actin‐binding protein, has been documented to be involved in endothelial injury and in the proliferation of vascular smooth muscle cells resulting from hypertension. However, the role of profilin‐1 in ADMA‐induced vascular injury in hypertension remains largely unknown. Forty healthy subjects and forty‐two matched patients with essential hypertension were enrolled, and the related indexes of vascular injury in plasma were detected. Rat aortic smooth muscle cells (RASMCs) were treated with different concentrations of ADMA for different periods of time and transfected with profilin‐1 small hairpin RNA to interrupt the expression of profilin‐1. To determine the role of the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway, RASMCs were pretreated with AG490 or rapamycin. The expression of profilin‐1 was tested using real‐time polymerase chain reaction (PCR) and western blot analysis. Cell proliferation was measured by flow cytometry and 3‐(4,5‐dimethylthiazol‐2yl)‐2,5‐diphenyltetrazoliumbromide assays. Compared with healthy subjects, the levels of ADMA and profilin‐1 were markedly elevated in hypertensive individuals, while the levels of NO were significantly decreased (p < 0.05). In vitro, studies showed ADMA‐induced profilin‐1 expression in a concentration‐ and time‐dependent manner in RASMCs (p < 0.05), concomitantly with promoting the proliferation of RASMCs. Furthermore, ADMA‐mediated proliferation of RASMCs and upregulation expression of profilin‐1 were inhibited by blockade of the JAK2/STAT3 pathway or knockdown of profilin‐1. Profilin‐1 implicated in the ADMA‐mediated vascular lesions in hypertension.

The relationship of asymmetric dimethylarginine levels with uncontrolled arterial hypertension and hypertension disease stage

“…Предыдущие исследования показали, что уровни асимметричного диметиларгинина (ADMA) тесно связаны с гипертонией, диабетом и сердечнососудистыми заболеваниями [16]. Резистентная АГ статистически значимо увеличивает риск развития ишемической болезни сердца, сердечной недостаточности, инсульта и хронической болезни почек, а также обусловливает более высокий риск серьезных неблагоприятных сердечно-сосудистых событий и повышенную смертность от всех причин.…”