Gao Pan, Qian De-Hui, Li Wei, Huang Lan
Department of Cardiology, XinQiao Hospital, The Third Medical Military University, Chongqing, 400037, China.
Mol Cell Biochem. 2009 Apr;324(1-2):165-72. doi: 10.1007/s11010-008-9995-y. Epub 2008 Dec 23.
Excessive proliferation of vascular smooth cells (VSMCs) plays a critical role in the pathogenesis of diverse vascular disorders, and inhibition of VSMCs proliferation has been proved to be beneficial to these diseases. In this study, we investigated the antiproliferative effect of B-type natriuretic peptide (BNP), a natriuretic peptide with potent antioxidant capacity, on rat aortic VSMCs, and the possible mechanisms involved. The results indicate that BNP potently inhibited AngiotensinII (AngII)-induced VSMCs proliferation, as evaluated by [(3)H]-thymidine incorporation assay. Consistently, BNP significantly decreased AngII-induced intracellular reactive oxygen species (ROS) and NAD(P)H oxidase activity. 8-Br-cGMP, a cGMP analog, mimicked these effects. To confirm its mechanism, siRNA of natriuretic peptide receptor-A(NRPA) strategy technology was used to block cGMP production in VSMCs, and siNPRA attenuated the inhibitory effects of BNP in VSMCs. Taken together, these results indicate that BNP was capable of inhibiting VSMCs proliferation by NPRA/cGMP pathway, which might be associated with the suppression of ROS production. These results might be related, at least partly, to the anti-oxidant property of BNP.
血管平滑肌细胞（VSMC）的过度增殖在多种血管疾病的发病机制中起关键作用，并且已证明抑制VSMC增殖对这些疾病有益。在本研究中，我们研究了具有强大抗氧化能力的利钠肽B型利钠肽（BNP）对大鼠主动脉VSMC的抗增殖作用及其可能的机制。结果表明，通过[³H] - 胸腺嘧啶核苷掺入试验评估，BNP能有效抑制血管紧张素II（AngII）诱导的VSMC增殖。同样，BNP显著降低了AngII诱导的细胞内活性氧（ROS）和NAD（P）H氧化酶活性。一种环磷酸鸟苷（cGMP）类似物8 - Br - cGMP模拟了这些作用。为了证实其机制，采用利钠肽受体 - A（NRPA）策略技术的小干扰RNA（siRNA）来阻断VSMC中的cGMP产生，并且siNPRA减弱了BNP对VSMC的抑制作用。综上所述，这些结果表明BNP能够通过NPRA/cGMP途径抑制VSMC增殖，这可能与抑制ROS产生有关。这些结果可能至少部分与BNP的抗氧化特性有关。
