A Clinical Perspective: Contribution of Dysfunctional Perivascular Adipose Tissue (PVAT) to Cardiovascular Risk

Aim. To determine the expression of adiponectin, leptin and I interleukin-6 (IL-6) in subcutaneous, epicardial and perivascular adipose tissue, depending on the presence of cardiovascular risk factors.Material and methods. The study included 90 patients with stable coronary artery disease (CAD) who underwent coronary artery bypass grafting. Samples of adipose tissue were obtained during surgery. The levels of matrix ribonucleic acid (mRNA) of the studied adipocytokines were determined in the presence/absence of the main cardiovascular risk factors.Results. Differences in the expression of genes of the studied adipocytokines in different sex and age groups of patients were revealed, depending on the tissue belonging of adipocytes. Expression of adiponectin in the epicardial and perivascular adipose tissue (EАT and PVAT, respectively), as well as of leptin in the PVAT was less pronounced in men. However, the level of IL-6 mRNA in the subcutaneous adipose tissue (SAT) of men was three times higher than in women, and in the PVAT it was lower. The maximum expression of leptin and IL-6 in the EAT and PVAT was found in persons aged 50-59 years. The presence of dyslipidemia is associated with a decrease in the expression of adiponectin in the EAT, PVAT, and IL-6 in the PVAT. In patients with hypertension (HTN), there was a low level of adiponectin mRNA in the EAT against the background of high leptin levels in the EAT and IL-6 in SAT and EAT. In hypertension with a duration of more than 20 years, there was a decrease in adiponectin expression and an increase in leptin in all types of AT. In smokers, an increase in the expression of adiponectin in the SAT, EAT, PVAT and leptin in the SAT, EAT was found.Conclusion. Associations of traditional cardiovascular risk factors with imbalance of adipocytokines of local fat depots in patients with CAD were revealed. The detected imbalance is manifested by a decrease in the expression of cardioprotective adiponectin in the EAT, PVAT, an increase in leptin and IL-6, which is an unfavorable sign. The presence of such risk factors as male sex, age of 50-59 years, dyslipidemia and hypertension in patients can enhance atherogenesis and contribute to the further progression of CAD.

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Perivascular Adipose Tissue (PVAT) in Health and Disease

10.3389/978-2-88945-603-1 ◽

2018 ◽

Keyword(s):

Adipose Tissue ◽

Perivascular Adipose Tissue ◽

Health And Disease

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Restoring Perivascular Adipose Tissue Function in Obesity Using Exercise

Cardiovascular Drugs and Therapy ◽

10.1007/s10557-020-07136-0 ◽

2021 ◽

Author(s):

Sophie N Saxton ◽

Lauren K Toms ◽

Robert G Aldous ◽

Sarah B Withers ◽

Jacqueline Ohanian ◽

...

Keyword(s):

Adipose Tissue ◽

Contractile Function ◽

Ex Vivo ◽

Vascular Complications ◽

Electrical Field Stimulation ◽

Organic Cation Transporter ◽

Nervous Stimulation ◽

Perivascular Adipose Tissue ◽

Contractile Effect ◽

Organic Cation Transporter 3

AbstractPurposePerivascular adipose tissue (PVAT) exerts an anti-contractile effect which is vital in regulating vascular tone. This effect is mediated via sympathetic nervous stimulation of PVAT by a mechanism which involves noradrenaline uptake through organic cation transporter 3 (OCT3) and β3-adrenoceptor-mediated adiponectin release. In obesity, autonomic dysfunction occurs, which may result in a loss of PVAT function and subsequent vascular disease. Accordingly, we have investigated abnormalities in obese PVAT, and the potential for exercise in restoring function.MethodsVascular contractility to electrical field stimulation (EFS) was assessed ex vivo in the presence of pharmacological tools in ±PVAT vessels from obese and exercised obese mice. Immunohistochemistry was used to detect changes in expression of β3-adrenoceptors, OCT3 and tumour necrosis factor-α (TNFα) in PVAT.ResultsHigh fat feeding induced hypertension, hyperglycaemia, and hyperinsulinaemia, which was reversed using exercise, independent of weight loss. Obesity induced a loss of the PVAT anti-contractile effect, which could not be restored via β3-adrenoceptor activation. Moreover, adiponectin no longer exerts vasodilation. Additionally, exercise reversed PVAT dysfunction in obesity by reducing inflammation of PVAT and increasing β3-adrenoceptor and OCT3 expression, which were downregulated in obesity. Furthermore, the vasodilator effects of adiponectin were restored.ConclusionLoss of neutrally mediated PVAT anti-contractile function in obesity will contribute to the development of hypertension and type II diabetes. Exercise training will restore function and treat the vascular complications of obesity.

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Transglutaminases Are Active in Perivascular Adipose Tissue

International Journal of Molecular Sciences ◽

10.3390/ijms22052649 ◽

2021 ◽

Vol 22 (5) ◽

pp. 2649

Author(s):

Alexis N. Orr ◽

Janice M. Thompson ◽

Janae M. Lyttle ◽

Stephanie W. Watts

Keyword(s):

Adipose Tissue ◽

Vascular Remodeling ◽

Coagulation Factor ◽

Sprague Dawley ◽

Rt Pcr ◽

Ideal Model ◽

Perivascular Adipose Tissue ◽

Tissue Sections ◽

Insight Into ◽

Immunohistochemical Analyses

Transglutaminases (TGs) are crosslinking enzymes best known for their vascular remodeling in hypertension. They require calcium to form an isopeptide bond, connecting a glutamine to a protein bound lysine residue or a free amine donor such as norepinephrine (NE) or serotonin (5-HT). We discovered that perivascular adipose tissue (PVAT) contains significant amounts of these amines, making PVAT an ideal model to test interactions of amines and TGs. We hypothesized that transglutaminases are active in PVAT. Real time RT-PCR determined that Sprague Dawley rat aortic, superior mesenteric artery (SMA), and mesenteric resistance vessel (MR) PVATs express TG2 and blood coagulation Factor-XIII (FXIII) mRNA. Consistent with this, immunohistochemical analyses support that these PVATs all express TG2 and FXIII protein. The activity of TG2 and FXIII was investigated in tissue sections using substrate peptides that label active TGs when in a catalyzing calcium solution. Both TG2 and FXIII were active in rat aortic PVAT, SMAPVAT, and MRPVAT. Western blot analysis determined that the known TG inhibitor cystamine reduced incorporation of experimentally added amine donor 5-(biotinamido)pentylamine (BAP) into MRPVAT. Finally, experimentally added NE competitively inhibited incorporation of BAP into MRPVAT adipocytes. Further studies to determine the identity of amidated proteins will give insight into how these enzymes contribute to functions of PVAT and, ultimately, blood pressure.

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Defining the lineage of thermogenic perivascular adipose tissue

Nature Metabolism ◽

10.1038/s42255-021-00380-0 ◽

2021 ◽

Author(s):

Anthony R. Angueira ◽

Alexander P. Sakers ◽

Corey D. Holman ◽

Lan Cheng ◽

Michelangella N. Arbocco ◽

...

Keyword(s):

Adipose Tissue ◽

Perivascular Adipose Tissue

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D Radiotranscriptomic analysis of perivascular adipose tissue quantifies vascular inflammation in covid-19 from routine CT angiograms: Stratification of “new UK variant” Infection and prediction of in-hospital outcomes

10.1136/heartjnl-2021-bcs.238 ◽

2021 ◽

Author(s):

Christos P Kotanidis ◽

Cheng Xie ◽

David Adlam ◽

Jonathan CL Rodrigues ◽

Muhammad Siddique ◽

...

Keyword(s):

Adipose Tissue ◽

Vascular Inflammation ◽

Hospital Outcomes ◽

Perivascular Adipose Tissue

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Role of Perivascular Adipose Tissue-Derived Adiponectin in Vascular Homeostasis

Cells ◽

10.3390/cells10061485 ◽

2021 ◽

Vol 10 (6) ◽

pp. 1485

Author(s):

Adrian Sowka ◽

Pawel Dobrzyn

Keyword(s):

Endothelial Cells ◽

Adipose Tissue ◽

Smooth Muscle ◽

Vascular Smooth Muscle ◽

Smooth Muscle Cells ◽

Vascular Smooth Muscle Cells ◽

Muscle Cells ◽

Vascular Wall ◽

Whole Body ◽

Perivascular Adipose Tissue

Studies of adipose tissue biology have demonstrated that adipose tissue should be considered as both passive, energy-storing tissue and an endocrine organ because of the secretion of adipose-specific factors, called adipokines. Adiponectin is a well-described homeostatic adipokine with metabolic properties. It regulates whole-body energy status through the induction of fatty acid oxidation and glucose uptake. Adiponectin also has anti-inflammatory and antidiabetic properties, making it an interesting subject of biomedical studies. Perivascular adipose tissue (PVAT) is a fat depot that is conterminous to the vascular wall and acts on it in a paracrine manner through adipokine secretion. PVAT-derived adiponectin can act on the vascular wall through endothelial cells and vascular smooth muscle cells. The present review describes adiponectin’s structure, receptors, and main signaling pathways. We further discuss recent studies of the extent and nature of crosstalk between PVAT-derived adiponectin and endothelial cells, vascular smooth muscle cells, and atherosclerotic plaques. Furthermore, we argue whether adiponectin and its receptors may be considered putative therapeutic targets.

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Epicardial adipose tissue: the genetics behind an emerging cardiovascular marker

European Heart Journal ◽

10.1093/ehjci/ehaa946.3583 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

J.A Sousa ◽

M.G Serrao ◽

M Temtem ◽

A Pereira ◽

M Santos ◽

...

Keyword(s):

Adipose Tissue ◽

Cardiovascular Risk ◽

Genetic Risk ◽

Epicardial Adipose Tissue ◽

Genetic Risk Score ◽

Renin Angiotensin System ◽

Epicardial Fat ◽

Angiotensin System ◽

Renin Angiotensin ◽

Genetic Burden

Abstract Background Increasing evidence points epicardial adipose tissue (EAT) as an emerging cardiovascular risk marker. Whether genetic polymorphisms are associated with a higher EAT burden is still unknow. Genetic risk score (GRS) is an emerging method that attempts to establish correlation between single nucleotide polymorphisms (SNPs) and clinical phenotypes. Aim Evaluate the role of genetic burden and its association to EAT. Methods 996 patients (mean age 59±8, 78% male) were prospectively enrolled in a single center. EAT was measured on cardiac CT using a modified simplified method. Patients were divided into 2 groups (above vs. below the median EAT volume). We studied different polymorphisms across the following gene-regulated pathways: oxidation, renin-angiotensin system, cellular, diabetes/obesity and dyslipidemia pathways. Genotyping was performed by TaqMan allelic discrimination assay. A multiplicative genetic risk score (mGRS) was constructed and represents the genetic burden of the different polymorphisms studied. To evaluate the relation between genetics and EAT volume, we compared both groups by: global mGRS, gene cluster/axis mGRS and individual SNPs. Results Patients with above-median EAT volume were older, had higher body mass index (BMI) and higher prevalence of hypertension, diabetes and dyslipidemia (p<0.05). Patients with higher EAT volumes presented a higher global mean GRS (p<0.001), with the latter remaining an independent predictor for higher EAT volumes (OR 1.3, 95% CI 1.2–1.5), alongside age and BMI. In the analysis by gene clusters, patients with more epicardial fat consistently presented a higher polymorphism burden (translated by a higher mGRS level) across numerous pathways: oxidation, renin-angiotensin system, cellular, diabetes/obesity and dyslipidemia. After adjusting for confounders and other univariate predictors of higher fat volume, the following have emerged as independently related to higher EAT volumes: mGRS comprising the genes of different clusters, age and BMI. Amongst the 33 genes analyzed, only MTHFR677 polymorphisms (a gene with a critical role in regulating plasma homocysteine levels) emerged as significantly related to higher EAT volumes in our population (OR 1.4, 95% CI: 1.100–1.684, p=0.005). Conclusion Patients with a higher polymorphism burden in genes involved in the oxidation, renin-angiotensin, cellular, diabetes/obesity and dyslipidemia pathways present higher levels of epicardial fat. This potential association seems to be independent from the expected association between epicardial fat and cardiovascular risk factors. To our knowledge, this is the first time such genetic profiling has been done, casting further insight into this complex matter. Funding Acknowledgement Type of funding source: None

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