管周脂肪紧密包裹于几乎所有的动脉血管的外膜周围，为血管提供机械支持固定和营养，近来发现其有抗血管收缩作用。Perilipin-1(Plin1)特异表达于脂肪细胞的脂滴表面，调节脂肪生成与分解；它的缺失导致类似脂肪营养不良症的脂肪组织减少表型，和类似肥胖症的脂肪分解与脂肪酸释放增加等脂肪功能紊乱。我们意外发现Plin1缺失小鼠发生高血压，但全身性调节因素如水盐代谢和激素正常。Plin1在血管组织不表达,因而无血管原位调节作用。我们推测Plin1缺失导致管周脂肪功能紊乱，局部脂肪因子和血管活性物质分泌失调、脂肪酸氧化过度产生氧化应激损伤，可损害毗邻血管平滑肌或/和内皮细胞，导致血管稳态失衡与张力调节异常，进而导致高血压发生。探讨病理条件下管周脂肪对血管稳态和血压调节的影响，有助于从新的视角解释脂肪功能紊乱性疾病如肥胖、脂肪营养不良症、特别是Plin1基因突变病人伴发高血压的病理生理机制。

All arteries are surrounded by a significant amount of perivascular adipose tissue, which has long been considered to serve primarily a supportive purpose. The studies in recent ten years show that the presence of perivascular adipose tissue decreases contractile responses to various vasoconstrictive agents, because perivascular fat can produce unidentified adipocyte derived relaxing factor as a critical regulator of vascular function. Perilipin-1 is the most abundant protein at the surface of the lipid droplets only in adipocyte, and regulates optimal lipid storage and triglyceride hydrolysis and release of free fatty acids from adipocytes to the circulation. Disruption of perilipin-1 gene in human and mice primarily disrupt adipose tissue function and cause low adiposity histologically like in lipodystrophy, but high basal lipolysis and fatty acid release from the adipocytes like in obesity. We identified that Perilipin-1 null mice occur hypertension, accompanied with the dysfunctions of adipose tissue. Because Perilipin-1 does not exist in vascular tissue and cell but expresses specifically in adipocytes, its deficiency may not affect blood vessels in situ. We hypotheses that perivascular adipose tissue dysfunction confers dysregulated local productions of inflammatory adipokines and vasoconstrictive hormones and thereby no long antagonizes vasoconstriction but in turn, confers a tonic vascular contractile response, which may be the basis for the hypertension occurred in Perilipin-1 null mice. Therefore, the aims of this proposal focus on how perivascular adipose tissue dysfunction affects vascular remodeling and vasoconstriction, and hence, early onset of hypertension, in Perilipin-1 null mice. Adipose-tissue dysfunction and vascular dysfunction and hypertension in Perilipin-1 null mice may mimic and mechanistically explain that occurring in obesity and lipodystrophy, two typical diseases of adipose tissue dysfunction.