School of Medicine, University of Crete, Heraklion, Greece.
Department of Medicine, Division of Cardiology, Montefiore Medical Center, Bronx, New York, USA.
Curr Opin Lipidol. 2019 Aug;30(4):307-313. doi: 10.1097/MOL.0000000000000610.
The inverse association between plasma high-density lipoprotein cholesterol (HDL-C) concentration and the incidence of cardiovascular disease (CVD) has been unequivocally proven by many epidemiological studies. There are several genetic disorders affecting HDL-C plasma levels, either providing atheroprotection or predisposing to premature atherosclerosis. However, up to date, there has not been any pharmacological intervention modulating HDL-C levels, which has been clearly shown to prevent the progression of CVD. Thus, clarifying the exact underlying mechanisms of inheritance of these genetic disorders that affect HDL is a current goal of the research, as key roles of molecular components of HDL metabolism and function can be revealed and become targets for the discovery of novel medications for the prevention and treatment of CVD.
Primary genetic disorders of HDL can be either associated with longevity or, in contrast, may lead to premature CVD, causing high morbidity and mortality to their carriers. A large body of recent research has closely examined the genetic disorders of HDL and new promising therapeutic strategies have been developed, which may be proven beneficial in patients predisposed to CVD in the near future.
We have reviewed recent findings on the inheritance of genetic disorders associated with high and low HDL-C plasma levels and we have discussed their clinical features, as well as information about new promising HDL-C-targeted therapies that are under clinical trials.
大量流行病学研究明确证实了血浆高密度脂蛋白胆固醇(HDL-C)浓度与心血管疾病(CVD)发生率之间的负相关关系。有几种遗传疾病会影响 HDL-C 的血浆水平,这些疾病要么提供动脉粥样硬化保护作用,要么导致早发性动脉粥样硬化。然而,迄今为止,尚无任何药物干预能调节 HDL-C 水平,而明确显示这种调节可预防 CVD 的进展。因此,阐明影响 HDL 的这些遗传疾病的确切遗传机制是目前研究的目标,因为可以揭示 HDL 代谢和功能的分子成分的关键作用,并成为发现用于预防和治疗 CVD 的新型药物的靶点。
HDL 的原发性遗传疾病可能与长寿相关,或者相反,可能导致早发性 CVD,使携带者的发病率和死亡率很高。大量最近的研究对与 HDL-C 血浆水平升高和降低相关的遗传疾病进行了详细检查,并开发了新的有前途的治疗策略,这些策略在不久的将来可能对易患 CVD 的患者有益。
我们回顾了与高和低 HDL-C 血浆水平相关的遗传疾病的遗传情况,并讨论了它们的临床特征,以及正在临床试验中的新的有前途的靶向 HDL-C 的治疗方法的信息。