Sex-biased and sex hormone-dependent regulation of apolipoprotein A1

Pronounced sex differences in the development and outcome (APOA1), the basic structural protein of high-density lipoprotein (HDL), is involved in key metabolic processes. However, its role in the pathogenesis of CVD is incompletely understood. The effects of biological sex on factors influencing the APOA1-lipid balance and the underlying mechanisms are also poorly understood. Here, we summarize evidence supporting sexbiased and sex hormone-dependent regulation of APOA1. In particular, we discuss sex-biased APOA1 genetic variation, sex differences in APOA1 regulation and cardiovascular physiology, and sex hormone-dependent regulation of APOA1 in cis- and transgender individuals. We put forward that studying the effects of biological sex will contribute to a better understanding of the role of APOA1 in cardiovascular physiology and its sex-biased association with CVD. Importantly, in situations of sex hormone therapy or inhibition, more sex-stratified data are required to inform clinical management of APOA1-related cardiovascular risk in a sexdependent manner.