scholarly journals 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

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

Abstract 16467: A Novel CT-derived Radiotranscriptomic Signature of Perivascular Adipose Tissue Stratifies COVID-19 Vascular Cytokine Burst and Predicts in Hospital Outcomes

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Christos P Kotanidis ◽  
Cheng Xie ◽  
Rafail Kotronias ◽  
Muhammad Siddique ◽  
Sheena Thomas ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Prognostic Value ◽  
Vascular Inflammation ◽  
Coronary Bypass ◽  
Composite Endpoint ◽  
Gradient Boosting ◽  
Hospital Death ◽  
Hospital Outcomes ◽  
Perivascular Adipose Tissue ◽  
Extreme Gradient Boosting

Introduction: COVID-19 is characterised by severe vascular inflammation. Perivascular adipose tissue (PVAT) has the ability to change its texture in response to vascular inflammation. Hypothesis: Computed Tomography Angiography (CTA)-based radiotranscriptomic phenotyping of PVAT may quantify COVID-19-induced vascular inflammation, predicting clinical outcomes. Methods: In Study 1, RNA sequencing of 60 internal mammary artery (IMA) biopsies from patients undergoing coronary bypass surgery was performed to build a transcriptomic fingerprint similar to that observed in COVID-19. This fingerprint was used to train an extreme gradient boosting algorithm, C19-RS, using CTA-derived radiomic features of PVAT around the IMA and descending thoracic aorta. In Study 2, C19-RS was validated in pulmonary artery CTAs from an independent cohort of 201 patients for COVID-19 detection and test its prognostic value in COVID-19. Results: Unsupervised hierarchical clustering of RNASeq data in Study 1 identified 2 clusters of vascular inflammation ( A ). Machine learning was used to train C19-RS to detect vascular inflammation based on 31 radiomic features. In study 2, 22 deaths and 32 ICU admissions were recorded. Patients with high C19-RS had an OR=3.11[95%CI:1.06-9.85] for COVID-19 adjusted for age, sex, risk factors, hsCRP, WBCC, COPD and CT tube voltage. C19-RS significantly improved the discrimination of a baseline model containing the above variables, for COVID-19 detection (delta[AUC]=0.03, p=0.008, B ). C19-RS was significantly associated with in-hospital death ( C ), and a composite endpoint of in-hospital death and ICU admission, with adjusted HR: 4.29 (95% CI: 1.48-13.52, p=0.009). Conclusion: COVID-19-induced vascular inflammation can be quantified by a radiotranscriptomic signature (C19-RS) derived from CT analysis of PVAT. C19-RS stratifies vascular inflammatory burden in COVID-19, and has striking prognostic value for in-hospital outcomes.

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 Perivascular Adipose Tissue Angiotensin II Type 1 Receptor Promotes Vascular Inflammation and Aneurysm Formation

Hypertension ◽  
2017 ◽  
Vol 70 (4) ◽  
pp. 780-789 ◽  
Author(s):  
Tomoki Sakaue ◽  
Jun Suzuki ◽  
Mika Hamaguchi ◽  
Chika Suehiro ◽  
Akiko Tanino ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Angiotensin Ii ◽  
Vascular Inflammation ◽  
Perivascular Adipose Tissue ◽  
Aneurysm Formation ◽  
Tissue Angiotensin

scholarly journals Wild blueberry consumption attenuates local inflammation in the perivascular adipose tissue of obese Zucker rats

2016 ◽  
Vol 41 (10) ◽  
pp. 1045-1051 ◽  
Author(s):  
Stefano Vendrame ◽  
Panagiotis Tsakiroglou ◽  
Aleksandra S. Kristo ◽  
Dale A. Schuschke ◽  
Dorothy Klimis-Zacas
Keyword(s):  
Adipose Tissue ◽  
Vascular Inflammation ◽  
Zucker Rats ◽  
Local Inflammation ◽  
Necrosis Factor Alpha ◽  
Perivascular Adipose Tissue ◽  
Factor Alpha ◽  
Obese Zucker Rats ◽  
The Impact ◽  
Wild Blueberry

Perivascular adipose tissue (PVAT) has been shown to play important roles in regulating vascular tone and linking local and systemic vascular inflammation. We examined the impact of PVAT on phenylephrine-mediated vasoconstriction in the aorta of obese Zucker rats (OZR) and their lean littermates (LZR) by comparing aortic rings with or without PVAT. Subsequently we placed OZR and LZR on a control (C) or an 8% wild blueberry (WB) diet and evaluated the effect of WB consumption on such response. PVAT-released adipokine concentrations were also measured as a function of WB diet. Maximal constrictor force (Fmax) in aortic rings without PVAT was significantly lower in OZR-C compared with LZR-C (0.41 ± 0.05 and 0.71 ± 0.06 g, respectively). Following WB diet, Fmax significantly increased in OZR (0.54 ± 0.06 g). In aortas with intact PVAT, Fmax was significantly lower in all groups (0.31 ± 0.06 OZR-C, 0.30 ± 0.05 OZR-WB, 0.29 ± 0.03 LZR-C, and 0.30 ± 0.04 g LZR-WB), but no difference was observed between treatments. PVAT concentrations of monocyte chemoactractant protein 1 (MCP-1), tumor necrosis factor alpha, and adiponectin were significantly higher in OZR compared with LZR (+102%, +108%, and +45%, respectively). Following WB diet, PVAT concentrations of interleukin-8 were significantly lower in both OZR (–37%) and LZR (–30%), while adiponectin concentrations significantly increased in both OZR (+11%) and LZR (+16%). MCP-1 concentrations significantly decreased (–31%) in the PVAT of OZR with the WB diet. WB consumption appears to attenuate local inflammation in PVAT, which may impact systemic vascular inflammation and endothelial function.

scholarly journals Perivascular Adipose Tissue Attenuation on Computed Tomography beyond the Coronary Arteries. A Systematic Review

Diagnostics ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1495
Author(s):  
Domenico Tuttolomondo ◽  
Chiara Martini ◽  
Francesco Nicolini ◽  
Francesco Formica ◽  
Alessandro Pini ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Systematic Review ◽  
Adipose Tissue ◽  
Coronary Arteries ◽  
Morphological Changes ◽  
Vascular Inflammation ◽  
Computed Tomography Imaging ◽  
Perivascular Adipose Tissue ◽  
Tomography Imaging ◽  
Vascular Beds

(1) Background: Perivascular adipose tissue attenuation, measured with computed tomography imaging, is a marker of mean local vascular inflammation since it reflects the morphological changes of the fat tissue in direct contact with the vessel. This method is thoroughly validated in coronary arteries, but few studies have been performed in other vascular beds. The aim of the present study is to provide insight into the potential application of perivascular adipose tissue attenuation through computed tomography imaging in extra-coronary arteries. (2) Methods: A comprehensive search of the scientific literature published in the last 30 years (1990–2020) has been performed on Medline. (3) Results: A Medline databases search for titles, abstracts, and keywords returned 3251 records. After the exclusion of repetitions and the application of inclusion and exclusion criteria and abstract screening, 37 studies were selected for full-text evaluation. Three papers were finally included in the systematic review. Perivascular adipose tissue attenuation assessment was studied in the internal carotid artery, ascending thoracic aorta, and abdominal aorta. (4) Conclusions: Perivascular adipose tissue attenuation seems to be an applicable parameter in all investigated vascular beds, generally with good inter-observer reproducibility.

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

Antioxidants ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 574 ◽  
Author(s):  
Andy W. C. Man ◽  
Yawen Zhou ◽  
Ning Xia ◽  
Huige Li
Keyword(s):  
Oxidative Stress ◽  
Adipose Tissue ◽  
Cardiovascular Diseases ◽  
Vascular Inflammation ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Cardiovascular Complications ◽  
Perivascular Adipose Tissue ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide ◽  
Vascular Oxidative Stress

Perivascular adipose tissue (PVAT) is the connective tissue surrounding most of the systemic blood vessels. PVAT is now recognized as an important endocrine tissue that maintains vascular homeostasis. Healthy PVAT has anticontractile, anti-inflammatory, and antioxidative roles. Vascular oxidative stress is an important pathophysiological event in cardiometabolic complications of obesity, type 2 diabetes, and hypertension. Accumulating data from both humans and experimental animal models suggests that PVAT dysfunction is potentially linked to cardiovascular diseases, and associated with augmented vascular inflammation, oxidative stress, and arterial remodeling. Reactive oxygen species produced from PVAT can be originated from mitochondria, nicotinamide adenine dinucleotide phosphate (NADPH) oxidases, and uncoupled endothelial nitric oxide synthase. PVAT can also sense vascular paracrine signals and response by secreting vasoactive adipokines. Therefore, PVAT may constitute a novel therapeutic target for the prevention and treatment of cardiovascular diseases. In this review, we summarize recent findings on PVAT functions, ROS production, and oxidative stress in different pathophysiological settings and discuss the potential antioxidant therapies for cardiovascular diseases by targeting PVAT.

scholarly journals Role of Inflammation in Vascular Disease-Related Perivascular Adipose Tissue Dysfunction

2021 ◽  
Vol 12 ◽  
Author(s):  
Yaozhi Chen ◽  
Zeyu Qin ◽  
Yaqiong Wang ◽  
Xin Li ◽  
Yang Zheng ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Blood Vessels ◽  
Vascular Inflammation ◽  
Vascular Diseases ◽  
The Body ◽  
Vascular Aging ◽  
Perivascular Adipose Tissue ◽  
Free Fatty Acid Metabolism ◽  
Anti Inflammatory

Perivascular adipose tissue (PVAT) is the connective tissue around most blood vessels throughout the body. It provides mechanical support and maintains vascular homeostasis in a paracrine/endocrine manner. Under physiological conditions, PVAT has anti-inflammatory effects, improves free fatty acid metabolism, and regulates vasodilation. In pathological conditions, PVAT is dysfunctional, secretes many anti-vasodilator factors, and participates in vascular inflammation through various cells and mediators; thus, it causes dysfunction involving vascular smooth muscle cells and endothelial cells. Inflammation is an important pathophysiological event in many vascular diseases, such as vascular aging, atherosclerosis, and hypertension. Therefore, the pro-inflammatory crosstalk between PVAT and blood vessels may comprise a novel therapeutic target for the prevention and treatment of vascular diseases. In this review, we summarize findings concerning PVAT function and inflammation in different pathophysiological backgrounds, focusing on the secretory functions of PVAT and the crosstalk between PVAT and vascular inflammation in terms of vascular aging, atherosclerosis, hypertension, diabetes mellitus, and other diseases. We also discuss anti-inflammatory treatment for potential vascular diseases involving PVAT.

Abstract 525: Transplanted LRP1-Deficient Periaortic Adipose Tissue Accelerates Atherosclerosis in Carotid Arteries of LDL Receptor Knockout Mice

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
David G Kuhel
Keyword(s):  
Adipose Tissue ◽  
Carotid Arteries ◽  
Vascular Inflammation ◽  
Ldl Receptor ◽  
Plasma Lipid ◽  
Fold Increase ◽  
Perivascular Adipose Tissue ◽  
Diet Induced Obesity ◽  
Atherosclerotic Lesions ◽  
Progression Of Atherosclerosis

Perivascular adipose tissue (PVAT) expands in obesity and is anatomically colocalized with atherosclerotic plaques in humans. Moreover, PVAT inflammation is upregulated in the setting of atherosclerosis. Local factors expressed in PVAT that influence adipose tissue inflammation and adipocyte expansion could modulate “outside-in” signals involved in the progression of atherosclerosis. Previous studies have shown that mice with adipose tissue deficient for the LDL receptor-related protein 1 ( ad-Lrp1 -/- ) display reduced adipocyte size and resistance to diet-induced obesity. To assess the contribution LRP1 in PVAT on the progression of atherosclerosis, we utilized an adipose allograft model. Briefly, PVAT taken from the aortic arch of ad-Lrp1 -/- and ad-Lrp1 +/+ mice were transplanted to the left common carotid arteries of LDL-receptor deficient (Ldlr -/- ) mice. Following a four week engraftment period mice were fed western diet for 12 weeks. Carotid arteries were then analyzed for lesion formation and the surrounding adipose tissue was analyzed for inflammatory markers. Carotid arteries of LDLR -/- mice receiving ad-LRP1 -/- transplanted adipose tissue exhibited >3 fold increase in plaque size compared to mice transplanted with ad-Lrp1 +/+ adipose tissues. Plasma lipid levels and atherosclerotic lesions in the contralateral carotid arteries, without PVAT transplant, were similar between the two recipient groups. When compared to wild-type, ad-Lrp1 -/- transplanted PVAT had a 1.9 fold increased number of CD68+ cells determined by both immunohistochemistry and mRNA. Pro-inflammatory cytokines, IL6 (2.7 fold), TNFα (4.7 fold), and MCP1 (2.1 fold) mRNA were also increased in ad-Lrp1 -/- transplanted PVAT. In addition, ad-Lrp1 -/- transplanted PVAT retained a decreased cell size as observed prior to and after transplantation indicating either increased triglyceride lipolysis or defective triglyceride storage. These findings suggest that deficiency of LRP1 in PVAT accelerates atherosclerosis via enhancing local vascular inflammation.

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