Endothelial Nitric Oxide Synthase in the Perivascular Adipose Tissue

Abstract

Perivascular adipose tissue (PVAT) is a special type of ectopic fat depot that adheres to most vasculatures. PVAT has been shown to exert anticontractile effects on the blood vessels and confers protective effects against metabolic and cardiovascular diseases. PVAT plays a critical role in vascular homeostasis via secreting adipokine, hormones, and growth factors. Endothelial nitric oxide synthase (eNOS; also known as NOS3 or NOSIII) is well-known for its role in the generation of vasoprotective nitric oxide (NO). eNOS is primarily expressed, but not exclusively, in endothelial cells, while recent studies have identified its expression in both adipocytes and endothelial cells of PVAT. PVAT eNOS is an important player in the protective role of PVAT. Different studies have demonstrated that, under obesity-linked metabolic diseases, PVAT eNOS may be even more important than endothelium eNOS in obesity-induced vascular dysfunction, which may be attributed to certain PVAT eNOS-specific functions. In this review, we summarized the current understanding of eNOS expression in PVAT, its function under both physiological and pathological conditions and listed out a few pharmacological interventions of interest that target eNOS in PVAT.

Endothelium-Derived Relaxing Factors and Endothelial Function: A Systematic Review

“…Introduced as unexpected evidence in adult humans in 2007 [ 61 ], the vasoprotective action of perivascular adipose tissue (PVAT) has been rediscovered as crucial in controlling vascular function in the presence and absence of a pathological condition [ 62 , 63 , 64 , 65 ]. Studies investigating the protective or damaging effect of perivascular adipose tissue are shown in Table 2 [ 53 , 54 , 55 , 56 , 57 ].…”

“…Therefore, PVAT eNOS has been shown to exert an important function that is included in the protective role of PVAT. Recently, Man et al demonstrated that, in the presence of obesity-related metabolic diseases, PVAT eNOS may be even more important than the share of endothelial eNOS in promoting obesity-induced vascular dysfunction, which can ultimately be attributed to certain specific functions of PVAT eNOS [ 65 ]. Finally, in a third report, it was suggested that obesity-induced loss of the anti-contractile effect of PVAT was reversed after calorie restriction in a mouse model [ 60 ].…”

Perivascular adipose tissue: Fine-tuner of vascular redox status and inflammation

“…eNOS expression has been identified in thoracic PVAT. Of note, any cardiovascular risk factors that lower availability of l -arginine and BH 4 promote eNOS uncoupling and therefore superoxide production [ 7 ]. Consequently, the overproduced ROS by PVAT during pathological conditions cause oxidative damage to adjacent vascular cells.…”

“…Ucp-1 ), presence of numerous lipid droplets, and high mitochondrial content [ 6 ]. Besides, certain PVAT, predominantly mesenteric PVAT, is more-white adipose tissue (WAT)-like, due to lower expression of thermogenic genes like UCP-1, presence of larger lipid droplets, and low mitochondrial number [ 7 ]. Meanwhile, certain PVAT, like coronary PVAT, is more beige adipose tissue (BeAT)-like because some brown adipocyte-associated genes, such as UCP-1 and carnitine palmitoyltransferase 1B, are differentially expressed when compared to those of BAT [ 8 ].…”

Reactive Oxygen Species in the Aorta and Perivascular Adipose Tissue Precedes Endothelial Dysfunction in the Aorta of Mice with a High-Fat High-Sucrose Diet and Additional Factors

“…However, Huige’s group and our group found that an HFHSD with insulin resistance induced minimal endothelial dysfunction in mouse aortas [ 5 ]. Huige revealed that an HFHSD impaired endothelial dysfunction in the aortas with perivascular adipose tissue (PVAT) due to eNOS uncoupling in PVAT [ 11 , 12 ]. We hypothesized that in an HFHSD, the perivascular component alone is impaired, and the additional factors impair not only PVAT but also the vessels themselves.…”