The pleiotropic effects of high-density lipoproteins and apolipoprotein A-I

The high density lipoprotein (HDL) fraction of human plasma consists of multiple subpopulations of spherical particles that are structurally uniform, but heterogeneous in terms of size, compo-sition and function. Numerous epidemiological studies have established that an elevated high density lipoprotein cholesterol (HDL-C) level is associated with decreased cardiovascular risk. However, with several recent randomised clinical trials of HDL-C raising agents failing to reduce cardiovascular events, contempo-rary research is transitioning towards clinical development of the cardioprotective functions of HDLs and the identification of func-tions that can be exploited for treatment of other diseases. This review describes the origins of HDLs and the causes of their compositional and functional heterogeneity. It then summarises current knowledge of how cardioprotective and other functions of HDLs are regulated. The final section of the review summarises recent advances in the clinical development of HDL-targeted therapies.(c) 2022 Elsevier Ltd. All rights reserved.