Comparative Proteomic Analysis of tPVAT during Ang II Infusion

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.

Angiotensin II Inhibits Adipogenic Differentiation and Promotes Mature Adipocyte Browning through the Corepressor CtBP1

“…It has been reported to be involved in oncogenic processes and effective recycling of synaptic vesicles [ 19 , 20 , 21 , 22 , 23 ]. We have recently reported that CtBP1 is one of the top 10 up-regulated proteins during Ang II-induced PVAT pathogenesis [ 6 ]. In addition, some reports show that CtBP1/2 is involved in controlling the switch from WAT to BAT [ 15 , 16 ].…”

“…There are many studies showing that PVAT dysfunction may induce several pathophysiological states such as obesity, atherosclerosis, or hypertension [ 3 , 4 , 5 ]. We previously reported that Ang II significantly changed thoracic PVAT (tPVAT) phenotype, making it irregular, and hypertrophy, which suggests that excessive activation of local RAS can lead to adipose tissue dysfunction [ 6 ]. Since adipocytes are the main cellular component of adipose tissue, we speculated that Ang II may affect the differentiation and function of adipocytes.…”

New Axially Chiral Molecular Scaffolds with Antibacterial Activities against Xanthomonas oryzae pv. oryzae for Protection of Rice

“…The in vitro and in vivo experiments against Xoo , SEM analysis, and label-free quantitative proteomics analysis were carried out, − and more details could be seen in the Supporting Information.…”