scholarly journals Site-specific impairment of perivascular adipose tissue on advanced atherosclerotic plaques using multimodal nonlinear optical imaging

2019 ◽  
Vol 116 (36) ◽  
pp. 17765-17774 ◽  
Author(s):  
Suho Kim ◽  
Eun-Soo Lee ◽  
Sang-Won Lee ◽  
Yong-Hoon Kim ◽  
Chul-Ho Lee ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Nonlinear Optical ◽  
Brown Fat ◽  
Atherosclerotic Plaques ◽  
Label Free ◽  
Perivascular Adipose Tissue ◽  
Site Specific ◽  
Knockout Mouse Model ◽  
Initial Stage ◽  
Vascular Physiology

Perivascular adipose tissue (PVAT), as a mechanical support, has been reported to systemically regulate vascular physiology by secreting adipokines and cytokines. How PVAT spatially and locally changes as atherosclerosis progresses is not known, however. We aimed to reveal the molecular changes in PVAT in advanced atherosclerosis based on multimodal nonlinear optical (MNLO) imaging. First, using an atherogenic apolipoprotein E knockout mouse model, we precisely assessed the browning level of thoracic PVAT via a correlative analysis between the size and number of lipid droplets (LDs) of label-free MNLO images. We also biochemically demonstrated the increased level of brown fat markers in the PVAT of atherosclerosis. In the initial stage of atherosclerosis, the PVAT showed a highly activated brown fat feature due to the increased energy expenditure; however, in the advanced stage, only the PVAT in the regions of the atherosclerotic plaques, not that in the nonplaque regions, showed site-specific changes. We found that p-smad2/3 and TGF-β signaling enhanced the increase in collagen to penetrate the PVAT and the agglomeration of LDs only at the sites of atherosclerotic plaques. Moreover, atherosclerotic thoracic PVAT (tPVAT) was an increased inflammatory response. Taken together, our findings show that PVAT changes differentially from the initial stages to advanced stages of atherosclerosis and undergoes spatial impairment focused on atherosclerotic plaques. Our study may provide insight into the local control of PVAT as a therapeutic target.

scholarly journals Role of Perivascular Adipose Tissue in Vascular Physiology and Pathology

Hypertension ◽  
2017 ◽  
Vol 69 (5) ◽  
pp. 770-777 ◽  
Author(s):  
Zhen Fang Huang Cao ◽  
Elina Stoffel ◽  
Paul Cohen
Keyword(s):  
Adipose Tissue ◽  
Perivascular Adipose Tissue ◽  
Vascular Physiology

scholarly journals Severe Brown Fat Lipoatrophy Aggravates Atherosclerotic Process in Male Mice

Endocrinology ◽  
2016 ◽  
Vol 157 (9) ◽  
pp. 3517-3528 ◽  
Author(s):  
Almudena Gómez-Hernández ◽  
Nuria Beneit ◽  
Óscar Escribano ◽  
Sabela Díaz-Castroverde ◽  
Gema García-Gómez ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Vascular Inflammation ◽  
Brown Fat ◽  
Visceral Adiposity ◽  
Perivascular Adipose Tissue ◽  
Metabolic Alterations ◽  
Brown Adipose ◽  
Apo E ◽  
Atherosclerotic Process ◽  
Adipose Organ

Obesity is one of the major risk factors for the development of cardiovascular diseases and is characterized by abnormal accumulation of adipose tissue, including perivascular adipose tissue (PVAT). However, brown adipose tissue (BAT) activation reduces visceral adiposity. To demonstrate that severe brown fat lipoatrophy might accelerate atherosclerotic process, we generated a new mouse model without insulin receptor (IR) in BAT and without apolipoprotein (Apo)E (BAT-specific IR knockout [BATIRKO];ApoE−/− mice) and assessed vascular and metabolic alterations associated to obesity. In addition, we analyzed the contribution of the adipose organ to vascular inflammation. Brown fat lipoatrophy induces visceral adiposity, mainly in gonadal depot (gonadal white adipose tissue [gWAT]), severe glucose intolerance, high postprandial glucose levels, and a severe defect in acute insulin secretion. BATIRKO;ApoE−/− mice showed greater hypertriglyceridemia than the obtained in ApoE−/− and hypercholesterolemia similar to ApoE−/− mice. BATIRKO;ApoE−/− mice, in addition to primary insulin resistance in BAT, also showed a significant decrease in insulin signaling in liver, gWAT, heart, aorta artery, and thoracic PVAT. More importantly, our results suggest that severe brown fat lipoatrophy aggravates the atherosclerotic process, characterized by a significant increase of lipid depots, atherosclerotic coverage, lesion size and complexity, increased macrophage infiltration, and proinflammatory markers expression. Finally, an increase of TNF-α and leptin as well as a decrease of adiponectin by BAT, gWAT, and thoracic PVAT might also be responsible of vascular damage. Our results suggest that severe brown lipoatrophy aggravates atherosclerotic process. Thus, BAT activation might protect against obesity and its associated metabolic alterations.

scholarly journals Defining the lineage of thermogenic perivascular adipose tissue

2020 ◽  
Author(s):  
Anthony R. Angueira ◽  
Alexander P. Sakers ◽  
Lan Cheng ◽  
Rojesh Shrestha ◽  
Chihiro Okada ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Smooth Muscle ◽  
Progenitor Cells ◽  
Ex Vivo ◽  
Brown Fat ◽  
Perivascular Adipose Tissue ◽  
Brown Adipose ◽  
Promising Therapeutic Approach

SummaryBrown adipose tissue can expend large amounts of energy and thus increasing its amount or activity is a promising therapeutic approach to combat metabolic disease. In humans, major deposits of brown fat cells are found intimately associated with large blood vessels, corresponding to perivascular adipose tissue (PVAT). However, the cellular origins of PVAT are poorly understood. Here, we applied single cell transcriptomic analyses, ex vivo adipogenesis assays, and genetic fate mapping in vivo to determine the identity of perivascular adipocyte progenitors. We found that thoracic PVAT initially develops from a fibroblastic lineage, comprising progenitor cells (Pdgfra+;Ly6a+;Pparg−) and preadipocytes (Pdgfra+;Ly6a−;Pparg+). Progenitors and preadipocytes in PVAT shared transcriptional similarity with analogous cell types in white adipose tissue, pointing towards a conserved adipose cell lineage hierarchy. Interestingly, the aortic adventitia of adult animals contained a novel population of adipogenic smooth muscle cells (Myh11+; Pdgfra−; Pparg+) possessing the capacity to generate adipocytes in vitro and in vivo. Taken together, these studies define distinct populations of fibroblastic and smooth muscle progenitor cells for thermogenic PVAT, providing a crucial foundation for developing strategies to augment brown fat activity.

scholarly journals Perivascular Adipose Tissue: Quantitative analysis by morphometry and stereology in rodents

2019 ◽  
Author(s):  
Felipe Demani Carneiro ◽  
Stephanie Christinne Sinder Mello ◽  
Emiliana Barbosa Marques ◽  
Rogerio Barbosa Magalhaes Barros ◽  
Christianne Bretas Vieira Scaramello ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Droplet Diameter ◽  
Volume Density ◽  
Brown Adipocytes ◽  
Perivascular Adipose Tissue ◽  
Know How ◽  
Morphological Aspects ◽  
White Adipocytes ◽  
Male Wistar Rats ◽  
Vascular Physiology

ABSTRACTThe perivascular adipose tissue (PVAT) provides mechanical support to blood vessels and modulates vascular physiology in obesity. Our goal is to provide a reproductive protocol using morphometric and stereological tools to assess PVAT morphology. The thoracic aorta from male Wistar rats (n=6) and C57BL/6 mice (n=7) underwent routine histological procedures, and two independent observers analyzed the same set of digital images. Agreement and reproducibility were assessed. Both observers showed that the diameter of rat brown adipocytes is larger than mice (P<0.002) as expected, and that the number density (QA) of brown adipocytes is smaller in rats compared to mice (P<0.01). Considering lipid droplets, observer #1 reported that in rats they were larger (P<0.005) and had a higher volume density (VV) than mice (P=0.035), but observer #2 found the opposite for lipid droplet diameter (P=0.001). White adipocytes were not found in the PVAT. Bland-Altman plots demonstrated agreement and reproducibility between observers since the means are close to the main difference (bias) and within the 95% limits of agreement. In conclusion, the methodology proposed can quantify morphological aspects of the aorta PVAT in rodents. It is reproducible and can be performed by both expert and inexperienced researchers, once they know how to recognize the structures of interest to be measured.

scholarly journals Restoring Perivascular Adipose Tissue Function in Obesity Using Exercise

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.

scholarly journals Transglutaminases Are Active in Perivascular Adipose Tissue

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.

scholarly journals Defining the lineage of thermogenic perivascular adipose tissue

2021 ◽  
Author(s):  
Anthony R. Angueira ◽  
Alexander P. Sakers ◽  
Corey D. Holman ◽  
Lan Cheng ◽  
Michelangella N. Arbocco ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Perivascular Adipose Tissue
Sign in / Sign up

Export Citation Format

Share Document