Abstract
Perivascular adipose tissue (PVAT) homeostasis plays an important role in maintaining vascular function, and PVAT dysfunction may induce several pathophysiological situations. In this study, we investigated the effect and mechanism of the local angiotensin II (Ang II) on PVAT. High-throughput comparative proteomic analysis, based on TMT labeling combined with LC-MS/MS, were performed on an in vivo Ang II infusion mice model to obtain a comprehensive view of the protein ensembles associated with thoracic PVAT (tPVAT) dysfunction induced by Ang II. In total, 5037 proteins were confidently identified, of which 4984 proteins were quantified. Compared with the saline group, 145 proteins were upregulated and 146 proteins were downregulated during Ang II-induced tPVAT pathogenesis. Bioinformatics analyses revealed that the most enriched GO terms were annotated as gene silencing, monosaccharide binding, and extracellular matrix. In addition, some novel proteins, potentially associated with Ang II infusion, were identified, such as acyl-CoA carboxylase α, very long-chain acyl-CoA synthetase (ACSVL), uncoupling protein 1 (UCP1), perilipin, RAS protein-specific guanine nucleotide-releasing factor 2 (RasGRF2), and hypoxia inducible factor 1α (HIF-1α). Ang II could directly participate in the regulation of lipid metabolism, transportation, and adipocyte differentiation by affecting UCP1 and perilipin. Importantly, the key KEGG pathways were involved in fatty acid biosynthesis, FABP3-PPARα/γ, RasGRF2-ERK-HIF-1α, RasGRF2-PKC-HIF-1α, and STAT3-HIF-1α axis. The present study provided the most comprehensive proteome profile of mice tPVAT and some novel insights into Ang II-mediated tPVAT dysfunction and will be helpful for understanding the possible relationship between local RAS activation and PVAT dysfunction.
Highlights
The renin–angiotensin–aldosterone system (RAAS) is involved in systemic blood pressure regulation and renal electrolyte homeostasis
Compared with the saline group, the angiotensin II (Ang II)-infused mice showed a substantial decrease in adipocyte size in thoracic PVAT (tPVAT)
In the aorta of rodents, Perivascular adipose tissue (PVAT) is primarily composed of white adipose tissue (WAT) in the abdominal region, while PVAT is primarily composed of brown adipose tissue (BAT) in the thoracic region [30]
Summary
The renin–angiotensin–aldosterone system (RAAS) is involved in systemic blood pressure regulation and renal electrolyte homeostasis. It is well accepted that Ang II mediates vascular smooth muscle cell (VSMC) proliferation, migration, and vascular remodeling [1,2]. We previously reported that Ang II regulates VSMC proliferation and vascular remodeling by RhoGDI signaling [3]. There is no detailed report on the effect of Ang II on PVAT (perivascular adipose tissue) structure and function. PVAT is an adipose tissue with endocrine and paracrine functions surrounding the blood vessels, such as the small mesenteric and femoral arteries or the large abdominal aorta (AA), and plays wide-ranging physiological roles on vascular environment stability and influences vascular pathogenesis [4,5]. PVAT has strong anti-atherosclerosis properties, induces non-shivering thermogenesis (NST), and metabolizes fatty acids by secreting various bioactive factors [6]. Under pathological conditions (such as obesity), PVAT loses its thermogenic ability and secretes pro-inflammatory
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