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。