Endothelial Nitric Oxide Synthase in the Perivascular Adipose Tissue

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  Figure 1. The crosstalk between PVAT and the vessel wall modulates vascular functions. PVAT releases vasoactive molecules, hormones, adipokines, and microvesicles. PVAT-derived relaxing factors (PVRFs) include leptin and adiponectin, hydrogen sulphide (H2S), hydrogen peroxide (H2O2), prostaglandins, NO, and angiotensin (Ang) 1–7. PVAT-derived contracting factors (PVCFs) include chemerin, calpastatin, 5-hydroxytryptamine (5-HT), norepinephrine (NE), AngII, and ROS. These factors from PVAT may reach the endothelial layer of blood vessels by either direct diffusion or via vasa vasorum or small media conduit networks connecting the medial layer with the underlying adventitia and modulate vasodilation and vasocontraction. PVAT plays a critical role in vascular homeostasis via secreting adipokine, hormones, and growth factors to modulate the proliferation of VSMCs. Adipocytes from PVAT also secrete different types of extracellular vesicles, including exosomes and microvesicles, which have also been shown to trigger early vascular remodeling in vascular inflammation. Under pathological conditions, PVAT becomes dysfunctional, and the secretion of the PVAT-derived factor becomes imbalanced which…

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  Figure 2. PVAT eNOS is an important modulator of vascular functions. Under HFD-induced obesity, the activity and expression of PVAT eNOS is significantly downregulated. PVAT eNOS may be even more important than endothelium eNOS in obesity-induced vascular dysfunction. Under normal condition, PVAT eNOS has multiple roles in regulating PVAT and vascular functions. PVAT eNOS can generate NO and regulate vasodilation via endothelium-dependent and endothelium-independent mechanisms. NO generated from PVAT eNOS can diffuse to the endothelium and activate EC, or directly activate sGC in the VSMC to evoke vasodilation. NO generated from PVAT eNOS can prevent vascular remodeling and stiffening via inhibiting VSMC proliferation and differentiation. PVAT eNOS is also responsible for modulating mitochondria biogenesis and browning of adipocytes in PVAT. In addition, NO generated from PVAT eNOS may regulate protein activities via SNO modification. Moreover, eNOS may, via protein–protein interactions and NO production, modulate miRNA-encapsulated microvesicles trafficking across PVAT. PVAT eNOS have a bidirectional regulation with adiponectin. Adiponectin is an important adipokine that modulates…