Proinflammatory Phenotype of Perivascular Adipocytes

Chatterjee, Tapan K.; Stoll, Lynn L.; Denning, Gerene M.; Harrelson, Allan; Blomkalns, Andra L.; Idelman, Gila; Rothenberg, Florence; Neltner, Bonnie; Romig‐Martin, Sara A.; Dickson, Eric W.; Rudich, Steven M.; Weintraub, Neal L.

doi:10.1161/circresaha.108.182998

Cited by 456 publications

(500 citation statements)

References 39 publications

(37 reference statements)

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“…[30][31][32] In addition, hypertrophy of medial layer in mesenteric artery with an accumulation of extracellular matrix proteins also contributes to the vessel change in GK rats. 33 Thus, alterations in mesenteric artery function and contexture are a main cause of the pathogenesis of mesenteric lesions in diabetes.…”

Section: Effects Of Lmwf On Endothelial Dysfunction and Mesentery Dammentioning

confidence: 99%

Low-molecular-weight fucoidan protects endothelial function and ameliorates basal hypertension in diabetic Goto-Kakizaki rats

Cui

Zheng

Zhang

et al. 2014

Laboratory Investigation

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Endothelial dysfunction, characterized by impairment of endothelial nitric oxide synthase (eNOS) and nitric oxide (NO) bioavailability, has been implicated in diabetic cardiovascular pathogenesis. In this study, low-molecular-weight fucoidan (LMWF), which has multiple biological activities including anti-inflammatory and anti-oxidative properties, was investigated for its protective effect against endothelial dysfunction in Goto-Kakizaki type 2 diabetic rats. LMWF (50, 100, or 200 mg/kg/day) or probucol (100 mg/kg/day) were given to diabetic rats for 12 weeks. Basal blood pressure, acetylcholine-or flow-mediated relaxation of mesenteric and paw arteries, endothelium-dependent dilation of aorta, eNOS phosphorylation, and NO production were measured using laser Doppler flowmetry, force myograph, hematoxylin and eosin staining, western blot analysis, and an NO assay. We found that LMWF robustly ameliorated the basal hypertension and impairment of endothelium-dependent relaxation in the aorta, as well as mesenteric and paw arteries in diabetic rats. In addition, the reduction in eNOS phosphorylation at Ser1177, eNOS expression, and NO production because of diabetes were partially reversed by LMWF treatment. However, probucol, a lipid-modifying drug with antioxidant properties, displayed only mild effects. Moreover, LMWF induced, in a dose-dependent manner, endotheliumdependent vasodilation and eNOS phosphorylation at Ser1177 in normal aorta, and also promoted Ser1177 phosphorylation and NO synthesis in primary cultured vasoendothelial cells. Thus, these data demonstrate for the first time that fucoidan protects vasoendothelial function and reduces basal blood pressure in type 2 diabetes rats via, at least in part, preservation of eNOS function. Fucoidan is therefore a potential candidate drug for protection of endothelium in diabetic cardiovascular complications. KEYWORDS: diabetes; endothelium-dependent vasodilation; endothelial nitric oxide synthase; low-molecular-weight fucoidan; nitric oxide Diabetic patients are at high risk of endothelial dysfunction and vascular lesions, because of multiple harmful stimuli, such as hyperglycemia, hyperlipidemia, and oxidative stress. These patients are susceptible to atherosclerosis, hypertension, and peripheral vascular disease. 1,2 It is well established that endothelium-derived nitric oxide (NO) maintains vascular homeostasis and health through vasodilation and protection of vasculature from various damaging agents. [3][4][5] Loss of NO induces increased activity of proinflammatory transcription factors, such as nuclear factor kappa B, resulting in expression of leukocyte adhesion molecules and production of chemokines and cytokines, which further promote endothelial inflammation and atherosclerosis. 5,6 Therefore, the endothelial dysfunction caused by imbalance of NO bioavailability in early-stage diabetes has been implicated as a sign or a predictor of a future cardiovascular event. [6][7][8] Mechanistically, a disturbance in endothelial NO synthase (eNOS) activity, refe...

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Section: Effects Of Lmwf On Endothelial Dysfunction and Mesentery Dammentioning

confidence: 99%

Low-molecular-weight fucoidan protects endothelial function and ameliorates basal hypertension in diabetic Goto-Kakizaki rats

Cui

Zheng

Zhang

et al. 2014

Laboratory Investigation

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“…In contrast to subcutaneous preadipocytes, which secreting significant amounts of anti-inflammatory adiponectin and very little interleukin-8 or monocyte chemoattractant protein-1 (MCP-1) during adipocytic differentiation, perivascular adipocytes (EAT, PAT, and TAT) release substantial amounts of proinflammatory interleukin-6, interleukin-8, and MCP-1 and very little adiponectin while exhibiting reduced adipocytic differentiation (20). These suggest that perivascular adipocytes modulate insulin sensitivity and cellular function in an autocrine or paracrine manner while attracting macrophages to the depot, further exacerbating inflammation and adipocyte dysfunction (20,21).…”

Section: Pathophysiologymentioning

confidence: 99%

“…These suggest that perivascular adipocytes modulate insulin sensitivity and cellular function in an autocrine or paracrine manner while attracting macrophages to the depot, further exacerbating inflammation and adipocyte dysfunction (20,21).…”

Section: Pathophysiologymentioning

confidence: 99%

Increased Epicardial, Pericardial, and Subcutaneous Adipose Tissue Is Associated with the Presence and Severity of Coronary Artery Calcium

Ahmadi¹,

Nabavi²,

Yang³

et al. 2010

Academic Radiology

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“…PVAT is known to release a wide range of adipokines believed to affect vascular function (13). The PVAT contains many receptor types, binds fluorescent ligands and can be easily visualized.…”

Section: Select a ʻRangeʼ Look-up-table (Lut)mentioning

confidence: 99%

Visualization and Analysis of Vascular Receptors Using Confocal Laser Scanning Microscopy and Fluorescent Ligands

Daly

Parmryd

McGrath

2012

Methods in Molecular Biology

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The use of fluorescent ligands to analyse receptor distribution is increasing in popularity. This is due to the ever growing number of fluorescent ligands and the increased sensitivity of microscope-based technologies. Image-analysis methods have advanced to a stage where quantification of fluorescent signals is relatively simple (if used appropriately). In this chapter we describe a method of analysing the 2D and 3D distribution of fluorescent ligands in segments of blood vessels. In addition, we introduce the issues surrounding the accurate analysis of colocalization of two different fluorescent ligands.

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Proinflammatory Phenotype of Perivascular Adipocytes

Cited by 456 publications

References 39 publications

Low-molecular-weight fucoidan protects endothelial function and ameliorates basal hypertension in diabetic Goto-Kakizaki rats

Low-molecular-weight fucoidan protects endothelial function and ameliorates basal hypertension in diabetic Goto-Kakizaki rats

Increased Epicardial, Pericardial, and Subcutaneous Adipose Tissue Is Associated with the Presence and Severity of Coronary Artery Calcium

Visualization and Analysis of Vascular Receptors Using Confocal Laser Scanning Microscopy and Fluorescent Ligands

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