Perivascular adipose tissue in autoimmune rheumatic diseases

Shi, Hong; Wu, Hanping; Winkler, Michael; Chantemèle, Eric J. Belin de; Lee, Richard; Kim, Ha Won; Weintraub, Neal L

doi:10.1016/j.phrs.2022.106354

Cited by 11 publications

(10 citation statements)

References 178 publications

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“…Like adipose depots in other anatomic locations, PVAT contains both preadipocytes and mature adipocytes with distinct gene expression and functional profiles ( 19 , 35 ). The PVAT surrounding thoracic aorta in healthy rodents and humans was reported to be enriched in beige adipocytes ( 36 ).…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, Wueest et al reported that Fas expression was increased in adipocytes isolated from insulinresistant mice and in adipose tissues of obese and diabetic patients, and that deletion of Fas in adipocytes decreased adipose tissue inflammation, hepatic steatosis, and insulin resistance induced by a high-fat diet (34). In order to exclude an effect of Fas-FasL signaling associated with the MRL/lpr background, we evaluated endothelial Like adipose depots in other anatomic locations, PVAT contains both preadipocytes and mature adipocytes with distinct gene expression and functional profiles (19,35). The PVAT surrounding thoracic aorta in healthy rodents and humans was reported to be enriched in beige adipocytes (36).…”

Section: Discussionmentioning

confidence: 99%

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Perivascular adipose tissue promotes vascular dysfunction in murine lupus

et al. 2023

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IntroductionPatients with systemic lupus erythematosus (SLE) are at elevated risk for Q10 cardiovascular disease (CVD) due to accelerated atherosclerosis. Compared to heathy control subjects, lupus patients have higher volumes and densities of thoracic aortic perivascular adipose tissue (PVAT), which independently associates with vascular calcification, a marker of subclinical atherosclerosis. However, the biological and functional role of PVAT in SLE has not been directly investigated.MethodsUsing mouse models of lupus, we studied the phenotype and function of PVAT, and the mechanisms linking PVAT and vascular dysfunction in lupus disease. Results and discussionLupus mice were hypermetabolic and exhibited partial lipodystrophy, with sparing of thoracic aortic PVAT. Using wire myography, we found that mice with active lupus exhibited impaired endothelium-dependent relaxation of thoracic aorta, which was further exacerbated in the presence of thoracic aortic PVAT. Interestingly, PVAT from lupus mice exhibited phenotypic switching, as evidenced by “whitening” and hypertrophy of perivascular adipocytes along with immune cell infiltration, in association with adventitial hyperplasia. In addition, expression of UCP1, a brown/beige adipose marker, was dramatically decreased, while CD45-positive leukocyte infiltration was increased, in PVAT from lupus mice. Furthermore, PVAT from lupus mice exhibited a marked decrease in adipogenic gene expression, concomitant with increased pro-inflammatory adipocytokine and leukocyte marker expression. Taken together, these results suggest that dysfunctional, inflamed PVAT may contribute to vascular disease in lupus.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Perivascular adipose tissue promotes vascular dysfunction in murine lupus

et al. 2023

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“…Coronary artery aneurysms and inflammatory cell infiltration have been observed in KD, and adipokines have been suggested to play a central role in its pathogenesis. A meta-analysis showed that resistin and adiponectin levels were significantly elevated in KD patients with coronary artery lesions compared to those without coronary involvement [97][98][99].…”

Section: Correlation Between Pcat and Coronary Arteritismentioning

confidence: 99%

Epicardial and Pericoronary Adipose Tissue, Coronary Inflammation, and Acute Coronary Syndromes

Napoli,

Pergola,

Basile

et al. 2023

JCM

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Vascular inflammation is recognized as the primary trigger of acute coronary syndrome (ACS). However, current noninvasive methods are not capable of accurately detecting coronary inflammation. Epicardial adipose tissue (EAT) and pericoronary adipose tissue (PCAT), in addition to their role as an energy reserve system, have been found to contribute to the development and progression of coronary artery calcification, inflammation, and plaque vulnerability. They also participate in the vascular response during ischemia, sympathetic stimuli, and arrhythmia. As a result, the evaluation of EAT and PCAT using imaging techniques such as computed tomography (CT), cardiac magnetic resonance (CMR), and nuclear imaging has gained significant attention. PCAT-CT attenuation, which measures the average CT attenuation in Hounsfield units (HU) of the adipose tissue, reflects adipocyte differentiation/size and leukocyte infiltration. It is emerging as a marker of tissue inflammation and has shown prognostic value in coronary artery disease (CAD), being associated with plaque development, vulnerability, and rupture. In patients with acute myocardial infarction (AMI), an inflammatory pericoronary microenvironment promoted by dysfunctional EAT/PCAT has been demonstrated, and more recently, it has been associated with plaque rupture in non-ST-segment elevation myocardial infarction (NSTEMI). Endothelial dysfunction, known for its detrimental effects on coronary vessels and its association with plaque progression, is bidirectionally linked to PCAT. PCAT modulates the secretory profile of endothelial cells in response to inflammation and also plays a crucial role in regulating vascular tone in the coronary district. Consequently, dysregulated PCAT has been hypothesized to contribute to type 2 myocardial infarction with non-obstructive coronary arteries (MINOCA) and coronary vasculitis. Recently, quantitative measures of EAT derived from coronary CT angiography (CCTA) have been included in artificial intelligence (AI) models for cardiovascular risk stratification. These models have shown incremental utility in predicting major adverse cardiovascular events (MACEs) compared to plaque characteristics alone. Therefore, the analysis of PCAT and EAT, particularly through PCAT-CT attenuation, appears to be a safe, valuable, and sufficiently specific noninvasive method for accurately identifying coronary inflammation and subsequent high-risk plaque. These findings are supported by biopsy and in vivo evidence. Although speculative, these pieces of evidence open the door for a fascinating new strategy in cardiovascular risk stratification. The incorporation of PCAT and EAT analysis, mainly through PCAT-CT attenuation, could potentially lead to improved risk stratification and guide early targeted primary prevention and intensive secondary prevention in patients at higher risk of cardiac events.

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“…Furthermore, obesity and adipose tissue deposition are important factors determining long-term disease prognosis and comorbidity development. For example, patients with SLE werereported to exhibit greater extent of visceral adipose tissue deposition than controls (Li et al 2019 ), which—together with the greater perivascular adipose depots reported in rheumatic diseases including SLE (Shi et al 2022 )—predisposes them for cardiovascular complications. As reported for other rheumatic diseases such as RA (Baker et al 2018 ), intermuscular adipose tissue deposition is also reported in SLE (Gamboa et al 2022 ) and contributes significantly to poorer long-term strength of patients.…”

Section: Cellular Pathology In Lupus Nephritis: the Bmp-7 Linkmentioning

confidence: 99%

Potential of bone morphogenetic protein-7 in treatment of lupus nephritis: addressing the hurdles to implementation

Smith,

du Toit,

Ollewagen

2023

Inflammopharmacol

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Up to 50% of systemic lupus erythematosus (SLE) patients world-wide develop lupus nephritis (LN). In low to middle income countries and in particular in sub-Saharan Africa, where SLE is prevalent with a more aggressive course, LN and end stage renal disease is a major cause of mortality. While developed countries have the funding to invest in SLE and LN research, patients of African descent are often underrepresented in clinical trials. Thus, the complex influence of ethnicity and genetic background on outcome of LN and SLE as a whole, is not fully understood. Several pathophysiological mechanisms including major role players driving LN have been identified. A large body of literature suggest that prevention of fibrosis—which contributes to chronicity of LN—may significantly improve long-term prognosis. Bone morphogenetic protein-7 (BMP-7) was first identified as a therapeutic option in this context decades ago and evidence of its benefit in various conditions, including LN, is ever-increasing. Despite these facts, BMP-7 is not being implemented as therapy in the context of renal disease. With this review, we briefly summarise current understanding of LN pathology and discuss the evidence in support of therapeutic potential of BMP-7 in this context. Lastly, we address the obstacles that need to be overcome, before BMP-7 may become available as LN treatment.

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Perivascular adipose tissue in autoimmune rheumatic diseases

Cited by 11 publications

References 178 publications

Perivascular adipose tissue promotes vascular dysfunction in murine lupus

Perivascular adipose tissue promotes vascular dysfunction in murine lupus

Epicardial and Pericoronary Adipose Tissue, Coronary Inflammation, and Acute Coronary Syndromes

Potential of bone morphogenetic protein-7 in treatment of lupus nephritis: addressing the hurdles to implementation

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