Perivascular Adipose Tissue as a Target for Antioxidant Therapy for Cardiovascular Complications

Abstract

<jats:p>Perivascular adipose tissue (PVAT) is the connective tissue surrounding most of the systemic blood vessels. PVAT is now recognized as an important endocrine tissue that maintains vascular homeostasis. Healthy PVAT has anticontractile, anti-inflammatory, and antioxidative roles. Vascular oxidative stress is an important pathophysiological event in cardiometabolic complications of obesity, type 2 diabetes, and hypertension. Accumulating data from both humans and experimental animal models suggests that PVAT dysfunction is potentially linked to cardiovascular diseases, and associated with augmented vascular inflammation, oxidative stress, and arterial remodeling. Reactive oxygen species produced from PVAT can be originated from mitochondria, nicotinamide adenine dinucleotide phosphate (NADPH) oxidases, and uncoupled endothelial nitric oxide synthase. PVAT can also sense vascular paracrine signals and response by secreting vasoactive adipokines. Therefore, PVAT may constitute a novel therapeutic target for the prevention and treatment of cardiovascular diseases. In this review, we summarize recent findings on PVAT functions, ROS production, and oxidative stress in different pathophysiological settings and discuss the potential antioxidant therapies for cardiovascular diseases by targeting PVAT.</jats:p>

Melatonin reverses the loss of the anticontractile effect of perivascular adipose tissue in obese rats

“…Overproduction of ROS in PVAT is a pathologic hallmark of obesity. For this reason, treatment with antioxidant compounds may be promising for restoring PVAT function in obesity 23 . In fact, PVAT has emerged as a potential pharmacological target in obesity.…”

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

“…NOS enzymes and in particular PVAT NOS-3 produce superoxide anion when uncoupled ( Vasquez-Vivar et al, 2003 ; Margaritis et al, 2013 ; Nobrega et al, 2019 ). Although several conditions are known to reduce NOS-3 activity in PVAT (lack of L-arginine, reduction in serine 1177 phosphorylation and acetylation; Man et al, 2020 ), BH4 oxidation and its reduced availability probably are the main cause for NOS-3 uncoupling in endothelial cells and most likely in PVAT as well ( Vasquez-Vivar et al, 2003 ; Marchesi et al, 2009 ). Since not all NOS molecules are uncoupled at the same time, some of them produce NO while some produce superoxide anion.…”

Circadian Rhythm in Adipose Tissue: Novel Antioxidant Target for Metabolic and Cardiovascular Diseases

“…Apart from the three types of adipose tissue mentioned above, perivascular adipose tissue (PVAT) is also a critical modulator of cardiovascular health [ 51 , 52 ]. PVAT is the ectopic fat depot surrounding most vasculature including large arteries and veins, small and resistance vessels, and skeletal muscle microvessels [ 52 ].…”

“…PVAT controls vascular tone on vessels through releasing various PVAT-derived relaxing factors (PVRFs) [ 53 ] and PVAT-derived contracting factors (PVCFs) [ 54 , 55 ]. Moreover, these PVAT-derived factors closely and directly affect vascular homeostatic processes, including vascular inflammation and oxidative stress, vascular tone, smooth muscle proliferation and migration and vascular remodeling [ 51 , 56 , 57 ].…”

“…Therefore, obesity engenders nutrient stress that alters mitochondrial function, while the elevated mitochondrial substrate load augments electron transport chain activity and ROS production [ 134 ]. The increased oxidative stress in adipose tissue alters the secretion of adipokines and leads to metabolic and cardiovascular complications [ 51 , 134 ]. As mentioned, secretion of adipokines is in circadian rhythm [ 135 ].…”