Department of Cardiology, University Leipzig - Heart Center Leipzig, Leipzig, Germany.
Department of Cardiology, University Leipzig - Heart Center Leipzig, Leipzig, Germany
Eur J Prev Cardiol. 2015 Jul;22(7):899-903. doi: 10.1177/2047487314541036. Epub 2014 Jun 23.
The functional properties of endothelial cells (ECs) for regulating nitric oxide (NO) bioavailability are important for normal endothelial function. Micro-RNAs (miRs) and especially angiomiRs regulate vascular integrity and angiogenesis. Besides regulation of reverse cholesterol transport, high-density lipoprotein (HDL) also stimulates NO generation by ECs. This function is impaired in patients with chronic heart failure (CHF) and can be attenuated by exercise training. The aim of the present study was to evaluate if HDL-induced miR expression is altered in CHF and if exercise training has an impact.
HDL was isolated from CHF patients in NYHA-IIIb (HDLNYHA) and healthy subjects (HDLHealthy) before and after exercise training. Subsequently ECs were incubated for 24 h with the isolated HDL and miR expression was quantified by RT-PCR.
HDL-induced expression of miR-126, miR-21 and miR-222 was significantly reduced in ECs incubated with HDLNYHA when compared to HDLHealthy. Exercise training attenuated this HDL-induced reduction of miR-126 and miR-21. HDL-induced expression of miR-221 and miR-214 was not altered in CHF compared to controls and no impact of exercise training was noted.
In conclusion, the present study shows that HDL isolated from CHF patients (NYHA-III) reduces the expression of pro-angiogenic miRs (i.e. miR-126 and miR-21), which may contribute to atherogenesis and endothelial dysfunction. However, exercise training was able to attenuate the HDL-induced reduction in pro-angiogenic miRs expression.
内皮细胞(ECs)调节一氧化氮(NO)生物利用度的功能特性对于正常的内皮功能至关重要。微小 RNA(miRs),尤其是血管生成 miR,调节血管完整性和血管生成。除了调节胆固醇逆转运外,高密度脂蛋白(HDL)还刺激 ECs 产生 NO。这种功能在慢性心力衰竭(CHF)患者中受损,运动训练可减弱这种功能。本研究旨在评估 CHF 患者中 HDL 诱导的 miR 表达是否发生改变,以及运动训练是否具有影响。
在运动训练前后,从 NYHA-IIIb 期(HDLNYHA)的 CHF 患者和健康受试者(HDLHealthy)中分离 HDL。随后,将分离的 HDL 孵育 ECs 24 h,并通过 RT-PCR 定量 miR 表达。
与 HDLHealthy 相比,用 HDLNYHA 孵育的 ECs 中,HDL 诱导的 miR-126、miR-21 和 miR-222 表达明显降低。运动训练减弱了这种由 HDL 诱导的 miR-126 和 miR-21 的减少。与对照组相比,CHF 中 HDL 诱导的 miR-221 和 miR-214 表达没有改变,且运动训练没有影响。
总之,本研究表明,从 CHF 患者(NYHA-III)中分离的 HDL 降低了促血管生成 miR(即 miR-126 和 miR-21)的表达,这可能导致动脉粥样硬化和内皮功能障碍。然而,运动训练能够减弱 HDL 诱导的促血管生成 miR 表达减少。