scholarly journals The Role of DPO-1 and XE991-Sensitive Potassium Channels in Perivascular Adipose Tissue-Mediated Regulation of Vascular Tone

2016 ◽  
Vol 7 ◽  
Author(s):  
Dmitry Tsvetkov ◽  
Jean-Yves Tano ◽  
Mario Kassmann ◽  
Ning Wang ◽  
Rudolf Schubert ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Potassium Channels ◽  
Vascular Tone ◽  
Perivascular Adipose Tissue ◽  
Regulation Of Vascular Tone

scholarly journals Role of Perivascular Adipose Tissue–Derived Methyl Palmitate in Vascular Tone Regulation and Pathogenesis of Hypertension

Circulation ◽  
2011 ◽  
Vol 124 (10) ◽  
pp. 1160-1171 ◽  
Author(s):  
Yuan-Chieh Lee ◽  
Hsi-Hsien Chang ◽  
Chih-Lung Chiang ◽  
Chin-Hung Liu ◽  
Jih-I Yeh ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Methyl Palmitate ◽  
Vascular Tone ◽  
Perivascular Adipose Tissue

Role of nitric oxide and hydrogen sulfide from perivascular adipose tissue in vascular tone of resistant mesenteric arteries from endotoxemic rats

Nitric Oxide ◽  
2012 ◽  
Vol 27 ◽  
pp. S39-S40
Author(s):  
Cheng-Ming Tsao ◽  
Ming-Shin Lee ◽  
Mei-Hui Liao ◽  
Chih-Chin Shih ◽  
Shiu-Jen Chen ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Adipose Tissue ◽  
Hydrogen Sulfide ◽  
Vascular Tone ◽  
Mesenteric Arteries ◽  
Perivascular Adipose Tissue

Abstract 3672: Loss of Perivascular Adipocyte Paracrine Function Leads to Increased Vascular Tone and Glucose Intolerance in Hypertension

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Kaivan Khavandi ◽  
Adam Greenstein ◽  
Sarah Withers ◽  
Kazuhiko Sonoyama ◽  
Sarah Lewis ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Metabolic Syndrome ◽  
Adipose Tissue ◽  
Vascular Tone ◽  
Tnf Alpha ◽  
Perivascular Adipose Tissue ◽  
The Metabolic Syndrome ◽  
Adipocyte Cell ◽  
Therapeutic Opportunity

In order to investigate the contribution of perivascular adipose tissue (PVAT) to arterial function, a total of 55 small arteries harvested from 35 skin biopsies of patients with Metabolic Syndrome and matched controls were mounted as ring preparations in a wire myograph. Contractility to cumulative doses of Norepinephrine in the presence or absence of PVAT showed an anticontractile effect in arteries from healthy volunteers (p=0.009), which was lost in patients with Metabolic Syndrome. Bioassay studies confirmed that PVAT releases a hydrophilic anticontractile factor in health, which is absent in obesity. Using a soluble fragment of the human Type 1 receptor, we identified that the anticontractile factor was adiponectin, which is the sole mediator of vasodilation, acting by increasing endothelial bioavailability of nitric oxide. Significant endothelial dysfunction was observed in patients with Metabolic Syndrome (p<0.001). Quantitative image analysis of adipose tissue revealed significantly increased adipocyte cell size in patients with Metabolic Syndrome, compared with healthy controls (p<0.006). There was immunohistochemical evidence of inflammation with upregulation of TNF-alpha receptor 1 in these patients (p<0.001). Application of exogenous TNF-alpha abolished the anticontractile effect of PVAT by reducing adiponectin bioavailability. Oxidative stress also induced by cytokines TNF-alpha and IL-6 but not IL-1, reduced adiponectin production from PVAT and increased basal tone. When the obese microenvironment was replicated in vitro by inflicting hypoxia on PVAT, adiponectin activity was lost but then rescued by incubation with cytokine antagonists. Further application of the adiponectin receptor fragment abolished PVAT relaxation. We conclude that in healthy arteries, PVAT releases adiponectin which reduces vascular tone. In obesity, this is lost by a cascade of adipocyte hypertrophy, hypoxia, inflammation and oxidative stress. The resulting vasoconstriction contributes to hypertension, hypertriglyceridaemia and insulin resistance. Direct targeting of adiponectin release from PVAT therefore provides a novel therapeutic opportunity in the Metabolic Syndrome.

scholarly journals SIRT3 (Sirtuin-3) Prevents Ang II (Angiotensin II)–Induced Macrophage Metabolic Switch Improving Perivascular Adipose Tissue Function

2020 ◽  
Author(s):  
Tong Wei ◽  
Jing Gao ◽  
Chenglin Huang ◽  
Bei Song ◽  
Mengwei Sun ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Angiotensin Ii ◽  
Metabolic Phenotype ◽  
Inflammasome Activation ◽  
Ang Ii ◽  
Sirtuin 3 ◽  
Metabolic Switch ◽  
Brown Adipocytes ◽  
Perivascular Adipose Tissue

Objective: Infiltrated macrophages actively promote perivascular adipose tissue remodeling and represent a dominant population in the perivascular adipose tissue microenvironment of hypertensive mice. However, the role of macrophages in initiating metabolic inflammation remains uncertain. SIRT3 (sirtuin-3), a NAD-dependent deacetylase, is sensitive to metabolic status and mediates adaptation responses. In this study, we investigated the role of SIRT3-mediated metabolic shift in regulating NLRP3 (Nod-like receptor family pyrin domain-containing 3) inflammasome activation. Approach and Results: Here, we report that Ang II (angiotensin II) accelerates perivascular adipose tissue inflammation and fibrosis, accompanied by NLRP3 inflammasome activation and IL (interleukin)-1β secretion in myeloid SIRT3 knockout (SIRT3 − / − ) mice. This effect is associated with adipose tissue mitochondrial dysfunction. In vitro studies indicate that the deletion of SIRT3 in bone marrow–derived macrophages induces IL-1β production by shifting the metabolic phenotype from oxidative phosphorylation to glycolysis. Mechanistically, SIRT3 deacetylates and activates PDHA1 (pyruvate dehydrogenase E1 alpha) at lysine 83, and the loss of SIRT3 leads to PDH activity decrease and lactate accumulation. Knocking down LDHA (lactate dehydrogenase A) or using carnosine, a buffer against lactic acid, attenuates IL-1β secretion. Furthermore, the blockade of IL-1β from macrophages into brown adipocytes restores thermogenic markers and mitochondrial oxygen consumption. Moreover, NLRP3 knockout (NLRP3 −/− ) mice exhibited reduced IL-1β production while rescuing the mitochondrial function of brown adipocytes and alleviating perivascular adipose tissue fibrosis. Conclusions: SIRT3 represents a potential therapeutic target to attenuate NLRP3-related inflammation. Pharmacological targeting of glycolytic metabolism may represent an effective therapeutic approach.

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