Thoracic perivascular adipose tissue inhibits VSMC apoptosis and aortic aneurysm formation in mice via the secretome of browning adipocytes  

作　　者：Chun-ling Huang Yu-na Huang Lei Yao Jun-ping Li Zeng-hui Zhang Zhao-qi Huang Si-xu Chen Yu-ling Zhang Jing-feng Wang Yang-xin Chen Zhao-yu Liu 

机构地区：[1]Medical Research Center,Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation,Sun Yat-Sen Memorial Hospital,Sun Yat-Sen University,Guangzhou 510120,China [2]Department of Cardiology,Guangdong Provincial Key Laboratory of Arrhythmia and Electrophysiology,Sun Yat-Sen Memorial Hospital,Sun Yat-Sen University,Guangzhou 510120,China

出　　处：《Acta Pharmacologica Sinica》2023年第2期345-355,共11页中国药理学报（英文版）

基　　金：supported by grants from the National Natural Sclence Foundation of China(82170492,81900387);Guangdong Basic and Applied Basic Research Found(2019A15150118061);Science and Technology Program of Guangzhou City of China(202102010302).

摘　　要：Abdominal aortic aneurysm(AAA)is a dangerous vascular disease without any effective drug therapies so far.Emerging evidence suggests the phenotypic differences in perivascular adipose tissue(PVAT)between regions of the aorta are implicated in the development of atherosclerosis evidenced by the abdominal aorta more vulnerable to atherosclerosis than the thoracic aorta in large animals and humans.The prevalence of thoracic aortic aneurysms(TAA)is much less than that of abdominal aortic aneurysms(AAA).In this study we investigated the effect of thoracic PVAT(T-PVAT)transplantation on aortic aneurysm formation and the impact of T-PVAT on vascular smooth muscle cells.Calcium phosphate-induced mouse AAA model was established.T-PVAT(20 mg)was implanted around the abdominal aorta of recipient mice after removal of endogenous abdominal PVAT(A-PVAT)and calcium phosphate treatment.Mice were sacrificed two weeks after the surgery and the maximum external diameter of infrarenal aorta was measured.We found that T-PVAT displayed a more BAT-like phenotype than A-PVAT;transplantation of T-PVAT significantly attenuated calcium phosphate-induced abdominal aortic dilation and elastic degradation as compared to sham control or A-PVAT transplantation.In addition,T-PVAT transplantation largely preserved smooth muscle cell content in the abdominal aortic wall.Co-culture of T-PVAT with vascular smooth muscle cells(VSMCs)significantly inhibited H_(2)O_(2)−or TNFαplus cycloheximide-induced VSMC apoptosis.RNA sequencing analysis showed that T-PVAT was enriched by browning adipocytes and anti-apoptotic secretory proteins.We further verified that the secretome of mature adipocytes isolated from T-PVAT significantly inhibited H_(2)O_(2)−or TNFαplus cycloheximide-induced VSMC apoptosis.Using proteomic and bioinformatic analyses we identified cartilage oligomeric matrix protein(COMP)as a secreted protein significantly increased in T-PVAT.Recombinant COMP protein significantly inhibited VSMC apoptosis.We conclude that T-PVAT exerts anti-apo

关 键 词：abdominal aortic aneurysm perivascular adipose tissue BROWNING vascular smooth muscle cells APOPTOSIS SECRETOME 

分 类 号：X70[环境科学与工程—环境工程]