NO, ROS, RAS, and PVAT: More Than a Soup of Letters

Abstract

Perivascular adipose tissue (PVAT) has recently entered in the realm of cardiovascular diseases as a putative target for intervention. Notwithstanding its relevance, there is still a long way before the role of PVAT in physiology and pathology is fully understood. The general idea that PVAT anti-contractile effect is beneficial and its pro-contractile effect is harmful is being questioned by several reports. The role of some PVAT important products or systems such as nitric oxide (NO), reactive oxygen species (ROS), and RAS may vary depending on the context, disease, place of production, etc., which adds doubts on how mediators of PVAT anti- and pro-contractile effects are called to action and their final result. This short review will address some points regarding NO, ROS, and RAS in the beneficial and harmful roles of PVAT.

Keywords: angiotensin; nitric oxide; perivascular adipose tissue; sepsis; superoxide; vascular dysfunction.

FIGURE 1

Some of the main actors present in endothelial cells (EC) and perivascular adipose tissue (PVAT) that influence smooth muscle cells (SMC) in the context of the present review. PVAT can also modulate endothelial function and influence the vascular tone. These actors are involved in the dual role of PVAT, namely, its anti-contractile (upper curves) and pro-contractile (lower curves) effects on vessel response, both relevant in health and disease. Enzymes are in red letters, mediators in blue, and receptors/effectors in purple. PVAT contains adipocytes, innervation (neurons) and immune cells (lymphocytes, macrophages, and eosinophils), and vessels (not shown). NOS-3, NOS endothelial isoform; NOS-1, NOS neuronal isoform; (NOS-2), NOS inducible isoform; NOX, NADPH oxidases; sGC, soluble guanylate cyclase; ACE, angiotensin-converting enzyme; ACE2, ACE isoform 2; NO, nitric oxide; O2^-, superoxide anion; H₂O₂, hydrogen peroxide; ROS/RNS, reactive oxygen and nitrogen species, respectively; RSNO, low-molecular weight and protein S-nitrosothiols; ANG-(1–7), angiotensin 1–7; ANG II, angiotensin II; cGMP, cyclic GMP; AT1, angiotensin AT1 receptor; AT2, angiotensin AT2 receptor; Mas, Mas receptor; ß3AR, beta-3 adrenergic receptor; PKG, protein kinase G.