Higher levels of adiponectin in vascular endothelial cells are associated with greater brachial artery flow-mediated dilation in older adults

Abstract

Adiponectin, an adipocyte-derived protein, exerts anti-atherosclerotic effects on the vascular endothelium. Recently adiponectin protein has been reported in murine vascular endothelial cells, however, whether adiponectin is present in human vascular endothelial cells remains unexplored. We sought to examine 1) adiponectin protein in vascular endothelial cells collected from older adults free of overt cardiovascular disease; 2) the relation between endothelial cell adiponectin and in vivo vascular endothelial function; and 3) the relation between endothelial cell adiponectin, circulating (plasma) adiponectin and related factors. We measured vascular endothelial function (brachial artery flow-mediated dilation using ultrasonography), vascular endothelial cell adiponectin (biopsy coupled with quantitative immunofluorescence) and circulating adiponectin (Mercodia, ELISA) in older, sedentary, non-smoking, men and women (55 – 79 years). We found that higher endothelial cell adiponectin was related with greater flow-mediated dilation (r=0.43, P<0.05) and greater flow-mediated dilation normalized for shear stress (r=0.56, P<0.01), but was not related with vascular smooth muscle responsiveness to nitric oxide (r=0.04, P=0.9). Vascular endothelial cell adiponectin was not related with circulating adiponectin (r=−0.14, P=0.6). Endothelial cell and circulating adiponectin were differentially associated with adiposity, metabolic and other factors, but both were inversely associated with renal function (r=0.44 to 0.62, P ≤ 0.04). In conclusion, higher endothelial cell adiponectin levels are associated with higher vascular endothelial function, independent of circulating adiponectin levels in older adults.

Sirtuin-1 and Its Relevance in Vascular Calcification

“…Sirt1 in PVAT is also proven to regulate adiponectin secretion through the interaction with FoxO1 protein [89]. Adiponectin is an adipocyte-derived protein that is important in regulating carbohydrate metabolism, and it also possesses anti-atherosclerotic characteristics on the vascular endothelium [90]. To sum up, Sirt1 protects against oxidative stress and inflammatory insult by preventing adipocytokine release through the adenosine monophosphate-activated protein kinase (AMPK) pathway or normalizing adiponectin secretion in PVAT [91].…”

“…In PVAT, resveratrol can ameliorate adipokine release from dysregulated PVAT in response to inflammatory insult by AMPK/Sirt1 in an interdependent manner [89]. Resveratrol can also alleviate oxidative stress-induced cytokine release from PVAT and, subsequently, can improve arterial wall hypertrophy and adventitial collagen I accumulation, which results in arterial stiffness in aged mice [90]. In hyperphosphatemia-induced VC in CKD, resveratrol can significantly alleviate VSMC senescence and VC by activation of Sirt1.…”

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

“…SIRT1 also regulates the secretion of adiponectin in PVAT through the interaction with forkhead box protein O1 (FOXO1) [139]. The SIRT1 activator resveratrol can also normalize oxidative stress-induced cytokine release from PVAT and prevent arterial remodeling in aged mice [140].…”

Acute effect of mineralocorticoid receptor antagonism on vascular function in healthy older adults

“…Plasma F 2 -isoprostanes, another marker of oxidative stress, were measured by the Vanderbilt University Eicosanoid Core Laboratory using gas chromatography-mass spectrometry, as previously described (Hwang et al 2013b; Milne et al 2007). Plasma adiponectin (hexameric and high-molecular-weight forms) was measured using a commercially-available ELISA kit (Mercodia, Sweden) (Yoo et al 2015). …”