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《工程(英文)》 >> 2023年 第20卷 第1期 doi: 10.1016/j.eng.2022.06.013

糖尿病发作后心脏脂蛋白脂肪酶的变化

Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, V6T 1Z3, Canada

收稿日期: 2022-01-14 修回日期: 2022-06-23 录用日期: 2022-06-30 发布日期: 2022-07-26

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摘要

由于心脏持续地收缩和舒张,需要大量的能量,其中脂肪酸(FA)是其三磷酸腺苷(ATP)的主要来源。但是,心脏无法制造这种底物,而是从多种来源获得脂肪酸,包括通过脂蛋白脂肪酶(LPL)的作用。脂蛋白脂肪酶在心肌细胞中产生,随后分泌到质膜上的硫酸乙酰肝素蛋白聚糖(HSPG)结合位点。然后为了将脂蛋白脂肪酶转移到内皮细胞管腔,糖基磷脂酰肌醇锚定的高密度脂蛋白结合蛋白1(GPIHBP1)与间质性脂蛋白脂肪酶结合,并将其转移到血管管腔,在那里脂蛋白脂肪酶可将循环中的甘油三酯分解为脂肪酸。内源性-β-葡萄糖醛酸酶乙酰肝素酶(Hpa)的独特之处在于,它是唯一已知的哺乳动物酶,可以裂解硫酸乙酰肝素,从而促进上述脂蛋白脂肪酶从心肌细胞HSPG中释放。在糖尿病中,一直认为心脏产生能量方式的改变是导致糖尿病性心肌病(DCM)的原因。糖尿病发展到中度后,随着葡萄糖利用率的降低,由于Hpa 作用的增强,心脏血管腔内的脂蛋白脂肪酶活性得到增强。虽然这种适应可能有助于补偿心脏对葡萄糖的利用不足,但从长期来看,它是具有毒性的,因为有害的脂质代谢物积聚,以及脂肪酸氧化增强和因此造成的氧化应激,最终导致细胞死亡。这与一种心脏保护生长因子——血管内皮生长因子B(VEGFB)的丧失同时发生。本文探讨了乙酰肝素酶、脂蛋白脂肪酶和血管内皮生长因子B之间的相互联系及其在糖尿病性心肌病中的潜在影响。鉴于缺乏基于机制的DCM治疗,了解这种心肌病的病理,以及脂蛋白脂肪酶的作用,将有助于我们推进其临床治疗。

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