Schoch Leonie, Badimon Lina, Vilahur Gemma
Cardiovascular Program, Institut de Recerca, Hospital Santa Creu i Sant Pau, 08025 Barcelona, Spain.
Faculty of Medicine, University of Barcelona (UB), 08036 Barcelona, Spain.
Biomedicines. 2021 Jul 12;9(7):805. doi: 10.3390/biomedicines9070805.
Increasing evidence has cast doubt over the HDL-cholesterol hypothesis. The complexity of the HDL particle and its proven susceptibility to remodel has paved the way for intense molecular investigation. This state-of-the-art review discusses the molecular changes in HDL particles that help to explain the failure of large clinical trials intending to interfere with HDL metabolism, and details the chemical modifications and compositional changes in HDL-forming components, as well as miRNA cargo, that render HDL particles ineffective. Finally, the paper discusses the challenges that need to be overcome to shed a light of hope on HDL-targeted approaches.
越来越多的证据对高密度脂蛋白胆固醇假说提出了质疑。高密度脂蛋白颗粒的复杂性及其已被证实的易重塑性为深入的分子研究铺平了道路。这篇前沿综述讨论了高密度脂蛋白颗粒的分子变化，这些变化有助于解释旨在干扰高密度脂蛋白代谢的大型临床试验为何失败，并详细阐述了形成高密度脂蛋白的成分以及微小RNA载体内的化学修饰和组成变化，正是这些变化使得高密度脂蛋白颗粒失效。最后，本文讨论了为给以高密度脂蛋白为靶点的方法带来希望之光而需要克服的挑战。
