Role of Perivascular Adipose Tissue for Sex Differences in Coronary Artery Disease and Spontaneous Coronary Artery Dissection (SCAD)

Premenopausal women are largely protected from vascular dysfunction and atherosclerosis, while the progression of coronary artery disease increases after menopause to become the leading cause of death overall with similar prevalence as seen in men. Menopause has emerged as a particularly vulnerable phase for vascular health that is accompanied by profound metabolic changes characterized by a rapid clustering of cardiovascular risk factors and a shift from subcutaneous towards visceral, paracardial, and perivascular fat accumulation. While investigations studying sex differences of cardiovascular disease have mostly focused on the interaction between the endothelium and the vascular wall, there is little information about the role of perivascular adipose tissue (PVAT). Recently, the concept that PVAT may also be functionally relevant has led to the discovery of multiple adipose-derived relaxing and contracting factors, as well as adipokines and cytokines that regulate vascular inflammation and arterial stiffening through paracrine mechanisms. Here, we review the role of sex in PVAT-dependent effects on vascular health and disease, including the potential role of sex hormones and sex chromosomes. We propose adverse functional changes in PVAT as a novel source of mediators contributing to the sex differences in the pathophysiology of atherosclerotic coronary artery disease, coronary vasospasm, and spontaneous coronary artery dissection (SCAD).