Department of Cardiology, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030, China.
Acta Biochim Biophys Sin (Shanghai). 2010 May 15;42(5):325-31. doi: 10.1093/abbs/gmq025.
Leptin is a peptide hormone primarily involved in the regulation of food intake and energy expenditure. Recent studies have suggested that leptin is one of the risk factors for cardiovascular diseases including atherosclerosis and hypertension. Vascular smooth muscle cells (VSMCs) play a vital role in arterial intimal thickening and vascular remodeling. In this study, we investigated the effect of leptin on VSMC cell-cycle regulation and the possible pathway. We found that leptin stimulated VSMC proliferation and increased cell progression to S and G2/M phases. The expression of cyclinD1, phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2), and nuclear factor (NF)-kappaBp65 was increased. Treatment of the cells with leptin antagonist triple mutant attenuated the leptininduced ERK1/2 and NF-kappaB activation. These results suggested that leptin stimulated VSMC proliferation by promoting transition from G1 to S phase and ERK1/2 and NF-kappaB pathway might contribute to this procession.
瘦素是一种主要参与调节食物摄入和能量消耗的肽类激素。最近的研究表明，瘦素是包括动脉粥样硬化和高血压在内的心血管疾病的危险因素之一。血管平滑肌细胞（VSMCs）在动脉内膜增厚和血管重塑中起着至关重要的作用。在这项研究中，我们研究了瘦素对 VSMC 细胞周期调控的影响及其可能的途径。我们发现瘦素刺激 VSMC 增殖，并增加细胞向 S 和 G2/M 期的进展。细胞周期蛋白 D1、磷酸化细胞外信号调节激酶 1/2（ERK1/2）和核因子（NF）-kappaBp65 的表达增加。用瘦素拮抗剂三突变体处理细胞可减弱瘦素诱导的 ERK1/2 和 NF-kappaB 激活。这些结果表明，瘦素通过促进从 G1 期向 S 期的过渡来刺激 VSMC 增殖，ERK1/2 和 NF-kappaB 途径可能有助于这一过程。
