Fondazione Toscana Gabriele Monasterio.
Department of Pharmacy, University of Parma.
J Atheroscler Thromb. 2017 Aug 1;24(8):853-862. doi: 10.5551/jat.37101. Epub 2016 Dec 15.
Circulating levels of high-density lipoprotein cholesterol (HDL-C) are decreased in patients with heart failure (HF). We tested whether HDL-C serum levels are associated with cardiac contractile dysfunction in a minipig HF model.
Blood samples were collected from 13 adult male minipigs: 1) before pacemaker implantation, 2) 10 days after surgery, and 3) 3 weeks after high-rate LV pacing. Serum cholesterol efflux capacity (CEC), an index of HDL functionality, was assessed through four mechanisms: ATP Binding Cassette transporter A1 (ABCA1), ATP Binding Cassette transporter G1 (ABCG1), Scavenger Receptor-Class B Type I (SR-BI) and Passive Diffusion (PD).
HDL-C serum levels significantly decrease in minipigs with HF compared with baseline (p＜0.0001). Serum CEC mediated by PD and SR-BI, but not ABCA1 or ABCG1, significantly decrease in animals with HF (p＜0.05 and p＜0.005, respectively).
HDL-C serum levels and partial serum CEC reduction may play a pathophysiological role in the cardiac function decay sustained by high-rate LV pacing, opening new avenues to understand of the pathogenesis of nonischemic myocardial remodeling.
高密度脂蛋白胆固醇（HDL-C）在心力衰竭（HF）患者中的循环水平降低。我们测试了 HDL-C 血清水平是否与小型猪 HF 模型中心脏收缩功能障碍有关。
从 13 只成年雄性小型猪中采集血液样本：1）在起搏器植入前，2）手术后 10 天，和 3）左心室高起搏 3 周后。通过四种机制评估血清胆固醇外排能力（CEC），即 HDL 功能的指标：ATP 结合盒转运蛋白 A1（ABCA1）、ATP 结合盒转运蛋白 G1（ABCG1）、清道夫受体-B 型 I（SR-BI）和被动扩散（PD）。
与基线相比，HF 小型猪的 HDL-C 血清水平显著降低（p＜0.0001）。HF 动物中 PD 和 SR-BI 介导的血清 CEC 显著降低，但 ABCA1 或 ABCG1 则没有（分别为 p＜0.05 和 p＜0.005）。
HDL-C 血清水平和部分血清 CEC 减少可能在左心室高起搏持续的心脏功能衰减中发挥病理生理作用，为理解非缺血性心肌重构的发病机制开辟了新途径。
