Adipose tissue plays pivotal roles in the development of hypertension,including white and brown adipocytes.Immunity and inflammation provide a bridge between adipose dysfunction and hypertensive target organ damage.We...Adipose tissue plays pivotal roles in the development of hypertension,including white and brown adipocytes.Immunity and inflammation provide a bridge between adipose dysfunction and hypertensive target organ damage.We firstly found that perivascular adipose tissue(PVAT)expressed abundant C3,which stimulated adventitial fibroblast migration and phenotype trans-differentiation.Subsequently,we showed that C5a regulated M1/M2 macrophage polarization and inhibited adiponectin production in the PVAT,which contributed to vascular inflammation in hypertension.展开更多
Perivascular adipose tissue (PVAT) surrounds the exterior of blood vessels and releases numerous substances such as adiponectin which positively modulate blood vessel tone. In some cardiovascular diseases such as diab...Perivascular adipose tissue (PVAT) surrounds the exterior of blood vessels and releases numerous substances such as adiponectin which positively modulate blood vessel tone. In some cardiovascular diseases such as diabetes and high blood pressure, the function of PVAT changes and we speculate that oxidant stress may play a role in this change. PVAT has the ability to generate both superoxide and nitric oxide and these can combine rapidly under physiological conditions to form peroxynitrite (ONOO-). In disease states, the production of ONOO- may be increased and so its effect on the function of PVAT is of great interest. Consequently, we studied the effects of acute addition of the oxidant species ONOO- on vascular tone and production of adiponectin by mouse thoracic aortic PVAT. Murine PVAT was immunostained for nitrotyrosine, indicating that ONOO- is formed in the PVAT. Exogenous ONOO- significantly increased the anticontractile effect of PVAT via increased adiponectin content but had no effect on eNOS expression or phosphorylation. These results suggest that generation of ONOO- within PVAT may be an important regulatory mechanism which influences the activity of PVAT. The effect of chronic exposure to raised levels of ONOO- on PVAT function remains to be determined.展开更多
Abdominal aortic aneurysm(AAA)is strongly correlated with obesity,partially due to the abnormal expansion of abdominal perivascular adipose tissue(PVAT).Cell death-inducing DNA fragmentation factor-like effector C(CID...Abdominal aortic aneurysm(AAA)is strongly correlated with obesity,partially due to the abnormal expansion of abdominal perivascular adipose tissue(PVAT).Cell death-inducing DNA fragmentation factor-like effector C(CIDEC),also known as fat-specific protein 27(FSP27)in rodents,is specifically expressed in adipose tissue where it mediates lipid droplet fusion and adipose tissue expansion.Whether and how CIDEC/FSP27 plays a role in AAA pathology remains elusive.Here,we show that FSP27 exacerbates obesity and angiotensinⅡ(AngⅡ)-induced AAA progression.FSP27 deficiency in mice inhibited high-fat diet-induced PVAT expansion and inflammation.Both global and adipose tissue-specific FSP27 ablation significantly decreased obesity-related AAA incidence.Deficiency of FSP27 in adipocytes abrogated matrix metalloproteinase-12(MMP12)expression in aortic tissues.Infiltrated macrophages,which partially colocalize with MMP12,were significantly decreased in the FSP27-deficient aorta.Mechanistically,knockdown of Fsp27 in 3T3-L1 adipocytes inhibited C-C motif chemokine ligand 2(CCL2)expression and secretion through a c-Jun N-terminal kinase(JNK)-dependent pathway,thereby leading to reduced induction of macrophage migration,while Cidec overexpression rescued this effect.Overall,our study demonstrates that CIDEC/FSP27 in adipose tissue contributes to obesity-related AAA formation,at least in part,by enhancing PVAT inflammation and macrophage infiltration,thus shedding light on its significance as a key regulator in the context of obesity-related AAA.展开更多
文摘Adipose tissue plays pivotal roles in the development of hypertension,including white and brown adipocytes.Immunity and inflammation provide a bridge between adipose dysfunction and hypertensive target organ damage.We firstly found that perivascular adipose tissue(PVAT)expressed abundant C3,which stimulated adventitial fibroblast migration and phenotype trans-differentiation.Subsequently,we showed that C5a regulated M1/M2 macrophage polarization and inhibited adiponectin production in the PVAT,which contributed to vascular inflammation in hypertension.
文摘Perivascular adipose tissue (PVAT) surrounds the exterior of blood vessels and releases numerous substances such as adiponectin which positively modulate blood vessel tone. In some cardiovascular diseases such as diabetes and high blood pressure, the function of PVAT changes and we speculate that oxidant stress may play a role in this change. PVAT has the ability to generate both superoxide and nitric oxide and these can combine rapidly under physiological conditions to form peroxynitrite (ONOO-). In disease states, the production of ONOO- may be increased and so its effect on the function of PVAT is of great interest. Consequently, we studied the effects of acute addition of the oxidant species ONOO- on vascular tone and production of adiponectin by mouse thoracic aortic PVAT. Murine PVAT was immunostained for nitrotyrosine, indicating that ONOO- is formed in the PVAT. Exogenous ONOO- significantly increased the anticontractile effect of PVAT via increased adiponectin content but had no effect on eNOS expression or phosphorylation. These results suggest that generation of ONOO- within PVAT may be an important regulatory mechanism which influences the activity of PVAT. The effect of chronic exposure to raised levels of ONOO- on PVAT function remains to be determined.
基金supported by the National Natural Science Foundation of China(32271334,32100945,and 81871228)the National Key R&D Program of China(2018YFA0506900 and 2018YFA0800301)+3 种基金Shanghai Basic Research Field Project“Science and Technology Innovation Action Plan”(21JC1400400)the Lingang Laboratory(LG-QS-202204-06)the High-Level Medicine Foundation of Shanghai Government(to P.L.)Shanghai Municipal Science and Technology Major Project(2017SHZDZX01).
文摘Abdominal aortic aneurysm(AAA)is strongly correlated with obesity,partially due to the abnormal expansion of abdominal perivascular adipose tissue(PVAT).Cell death-inducing DNA fragmentation factor-like effector C(CIDEC),also known as fat-specific protein 27(FSP27)in rodents,is specifically expressed in adipose tissue where it mediates lipid droplet fusion and adipose tissue expansion.Whether and how CIDEC/FSP27 plays a role in AAA pathology remains elusive.Here,we show that FSP27 exacerbates obesity and angiotensinⅡ(AngⅡ)-induced AAA progression.FSP27 deficiency in mice inhibited high-fat diet-induced PVAT expansion and inflammation.Both global and adipose tissue-specific FSP27 ablation significantly decreased obesity-related AAA incidence.Deficiency of FSP27 in adipocytes abrogated matrix metalloproteinase-12(MMP12)expression in aortic tissues.Infiltrated macrophages,which partially colocalize with MMP12,were significantly decreased in the FSP27-deficient aorta.Mechanistically,knockdown of Fsp27 in 3T3-L1 adipocytes inhibited C-C motif chemokine ligand 2(CCL2)expression and secretion through a c-Jun N-terminal kinase(JNK)-dependent pathway,thereby leading to reduced induction of macrophage migration,while Cidec overexpression rescued this effect.Overall,our study demonstrates that CIDEC/FSP27 in adipose tissue contributes to obesity-related AAA formation,at least in part,by enhancing PVAT inflammation and macrophage infiltration,thus shedding light on its significance as a key regulator in the context of obesity-related AAA.
