RNA sequencing reveals perivascular adipose tissue plasticity in response to angiotensin II

Wang, Zhenguo; Lu, Haocheng; Garcia-Barrio, Minerva T.; Guo, Yanhong; Zhang, Jifeng; Chen, Y Eugene; Chang, Lin

doi:10.1016/j.phrs.2022.106183

Cited by 12 publications

(10 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Samples were then sent to the Advanced Genomics Core of U-M Biomedical Research Core Facilities for next-generation sequencing and quality control analysis. The data analysis follows a previously published paper [ 17 ].…”

Section: Methodsmentioning

confidence: 99%

Myeloid TM6SF2 Deficiency Inhibits Atherosclerosis

Zhu

Liang

et al. 2022

Cells

Self Cite

View full text Add to dashboard Cite

Genetic variants in transmembrane 6 superfamily member 2 (TM6SF2), such as E167K, are associated with atherosclerotic cardiovascular disease (ASCVD). Chronic inflammation and lipid-laden macrophage foam cell formation are the central pathogeneses in the development of atherosclerosis. This study was undertaken to illustrate the biological function of TM6SF2 in macrophages and its role during atherosclerosis development. We generated myeloid cell-specific Tm6sf2 knockout mice on ApoE-deficient background (LysM Cre+/Tm6sf2fl/fl/ApoE−/−, TM6 mKO) with littermate LysM Cre−/Tm6sf2fl/fl/ApoE−/− (Control) mice as controls. Mice were fed a Western diet for 12 weeks to induce atherosclerosis. Myeloid Tm6sf2 deficiency inhibited atherosclerosis and decreased foam cells in the plaques without changing the plasma lipid profile. RNA sequencing of bone marrow-derived macrophages (BMDMs) from TM6 mKO mice demonstrated the downregulation of genes associated with inflammation, cholesterol uptake, and endoplasmic reticulum (ER) stress. TM6SF2 was upregulated by oxidized low-density lipoprotein (oxLDL) in macrophages. Silencing TM6SF2 in THP-1-derived macrophages and Tm6sf2 deficiency in BMDMs reduced inflammatory responses and ER stress and attenuated cholesterol uptake and foam cell formation, while the overexpression of TM6SF2 showed opposite effects. In conclusion, myeloid TM6SF2 deficiency inhibits atherosclerosis development and is a potential therapeutic target for the treatment of atherogenesis.

show abstract

Section: Methodsmentioning

confidence: 99%

Myeloid TM6SF2 Deficiency Inhibits Atherosclerosis

Zhu

Liang

et al. 2022

Cells

Self Cite

View full text Add to dashboard Cite

show abstract

“…Furthermore, the blockade of both AT1R and AT2R restores the loss of PVAT anti-contractile effect in a rat model of heart failure caused by the overactivation of ACE1/angiotensin II/AT1R and AT2R pathway in PVAT [ 197 ]. Finally, angiotensin II has been linked to different pro-inflammatory phenotypes of PVAT that could be counteracted by PVAT browning [ 198 ]. Conversely, the contribution of angiotensin II to the loss of PVAT compensatory vasodilation during metabolic syndrome progression was ruled out as azilsartan, a potent AT1R antagonist, improves acetylcholine-induced vasodilation independently of the presence of PVAT [ 199 ].…”

Section: Pvat-derived Pro-contractile Factorsmentioning

confidence: 99%

Perivascular Adipose Tissue and Vascular Smooth Muscle Tone: Friends or Foes?

Ahmed

Bibi

Valoti

et al. 2023

Cells

View full text Add to dashboard Cite

Perivascular adipose tissue (PVAT) is a specialized type of adipose tissue that surrounds most mammalian blood vessels. PVAT is a metabolically active, endocrine organ capable of regulating blood vessel tone, endothelium function, vascular smooth muscle cell growth and proliferation, and contributing critically to cardiovascular disease onset and progression. In the context of vascular tone regulation, under physiological conditions, PVAT exerts a potent anticontractile effect by releasing a plethora of vasoactive substances, including NO, H2S, H2O2, prostacyclin, palmitic acid methyl ester, angiotensin 1-7, adiponectin, leptin, and omentin. However, under certain pathophysiological conditions, PVAT exerts pro-contractile effects by decreasing the production of anticontractile and increasing that of pro-contractile factors, including superoxide anion, angiotensin II, catecholamines, prostaglandins, chemerin, resistin, and visfatin. The present review discusses the regulatory effect of PVAT on vascular tone and the factors involved. In this scenario, dissecting the precise role of PVAT is a prerequisite to the development of PVAT-targeted therapies.

show abstract

“…However, in certain disease states, PVAT can promote atherosclerosis through the secretion of proinflammatory molecules [ 75 ]. Elevated angiotensin II is the main atherogenic component of the renin-angiotensin-aldosterone system [ 76 ]. Angiotensin II administration in mice elevated inflammation and reduced browning in PVAT [ 76 ].…”

Section: Metabolic Effects Of Mitoneet In Cardioprotectionmentioning

confidence: 99%

“…Elevated angiotensin II is the main atherogenic component of the renin-angiotensin-aldosterone system [ 76 ]. Angiotensin II administration in mice elevated inflammation and reduced browning in PVAT [ 76 ]. Conversely, PVAT from mitoNEET-Tg mice exhibits a more brown-like phenotype with some resistance to angiotensin II-induced inflammation [ 76 ].…”

Section: Metabolic Effects Of Mitoneet In Cardioprotectionmentioning

confidence: 99%

“…Angiotensin II administration in mice elevated inflammation and reduced browning in PVAT [ 76 ]. Conversely, PVAT from mitoNEET-Tg mice exhibits a more brown-like phenotype with some resistance to angiotensin II-induced inflammation [ 76 ]. Moreover, the brown adipose-specific overexpression of mitoNEET resulted in perivascular adipose tissue (PVAT) with increased thermogenesis, an anti-inflammatory response, and prevention of the development of atherosclerosis upon high-fat diet (HFD) feeding [ 77 ].…”

Section: Metabolic Effects Of Mitoneet In Cardioprotectionmentioning

confidence: 99%

See 1 more Smart Citation

MitoNEET Provides Cardioprotection via Reducing Oxidative Damage and Conserving Mitochondrial Function

Tam,

Sweeney

2023

IJMS

View full text Add to dashboard Cite

Cardiometabolic diseases exert a significant health impact, leading to a considerable economic burden globally. The metabolic syndrome, characterized by a well-defined cluster of clinical parameters, is closely linked to an elevated risk of cardiovascular disease. Current treatment strategies often focus on addressing individual aspects of metabolic syndrome. We propose that exploring novel therapeutic approaches that simultaneously target multiple facets may prove more effective in alleviating the burden of cardiometabolic disease. There is a growing body of evidence suggesting that mitochondria can serve as a pivotal target for the development of therapeutics aimed at resolving both metabolic and vascular dysfunction. MitoNEET was identified as a binding target for the thiazolidinedione (TZD) class of antidiabetic drugs and is now recognized for its role in regulating various crucial cellular processes. Indeed, mitoNEET has demonstrated promising potential as a therapeutic target in various chronic diseases, encompassing cardiovascular and metabolic diseases. In this review, we present a thorough overview of the molecular mechanisms of mitoNEET, with an emphasis on their implications for cardiometabolic diseases in more recent years. Furthermore, we explore the potential impact of these findings on the development of novel therapeutic strategies and discuss potential directions for future research.

show abstract

RNA sequencing reveals perivascular adipose tissue plasticity in response to angiotensin II

Cited by 12 publications

References 55 publications

Myeloid TM6SF2 Deficiency Inhibits Atherosclerosis

Myeloid TM6SF2 Deficiency Inhibits Atherosclerosis

Perivascular Adipose Tissue and Vascular Smooth Muscle Tone: Friends or Foes?

MitoNEET Provides Cardioprotection via Reducing Oxidative Damage and Conserving Mitochondrial Function

Contact Info

Product

Resources

About