title: Spontaneous hypertension occurs with adipose tissue dysfunction in perilipin-1 null mice.
abstract: Perilipin-1 (Plin1) coats lipid droplets exclusively in adipocytes and regulates two principle functions of adipose tissue, triglyceride storage and hydrolysis, which are disrupted upon Plin1 deficiency. In the present study, we investigated the alterations in systemic metabolites and hormones, vascular function and adipose function in spontaneous hypertensive mice lacking perilipin-1 (Plin1-/-). Plin1-/- mice developed spontaneous hypertension without obvious alterations in systemic metabolites and hormones. Plin1 expressed only in adipose cells but not in vascular cells, so its ablation would have no direct effect in situ on blood vessels. Instead, Plin1-/- mice showed dysfunctions of perivascular adipose tissue (PVAT), a fat depot that anatomically surrounds systemic arteries and has an anticontractile effect. In Plin1-/- mice, aortic and mesenteric PVAT were reduced in mass and adipocyte derived relaxing factor secretion, but increased in basal lipolysis, angiotensin II secretion, macrophage infiltration and oxidative stress. Such multiple culprits impaired the anticontractile effect of PVAT to promote vasoconstriction of aortic and mesenteric arteries of Plin1-/- mice. Furthermore, arterial vessels of Plin1-/- mice showed increasing angiotensin II receptor type 1, monocyte chemotactic protein-1 and interlukin-6 expression, structural damage of endothelial and smooth muscle cells, along with impaired endothelium-dependent relaxation. Hypertension in Plin1-/- mice might occur as a deleterious consequence of PVAT dysfunction. This finding provides the direct evidence that links dysfunctional PVAT to vascular dysfunction and hypertension, particularly in pathophysiological states. This hypertensive mouse model might mimic and explain the hypertension occurring in patients with adipose tissue dysfunction, particularly with Plin1 mutations.
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Beijing 100191, China.
authors.forename: Liangqiang
authors.initials: L
authors.lastname: Zou
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Beijing 100191, China.
authors.forename: Weiyi
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Beijing 100191, China.
authors.forename: Shangxin
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Beijing 100191, China.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Beijing 100191, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Lyv
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Beijing 100191, China.
authors.forename: Congkuo
authors.initials: C
authors.lastname: Du
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Beijing 100191, China.
authors.forename: Xueying
authors.initials: X
authors.lastname: Su
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Beijing 100191, China. Electronic address: bingeng@bjmu.edu.cn.
authors.forename: Bin
authors.initials: B
authors.lastname: Geng
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Beijing 100191, China. Electronic address: xug@bjmu.edu.cn.
authors.forename: Guoheng
authors.initials: G
authors.lastname: Xu
mesh_terms: D017667:Adipocytes / Q000378:metabolism / Q000473:pathology; D000273:Adipose Tissue / Q000098:blood supply / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D017353:Gene Deletion; D006973:Hypertension / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D007249:Inflammation / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D000070778:Perilipin-1 / Q000235:genetics*; D014661:Vasoconstriction; D014664:Vasodilation
chemical_list: D000070778:Perilipin-1
keywords: Hypertension; Inflammation; Oxidative stress; Perilipin; Perivascular adipose tissue