高血压是最常见的慢性疾病之一, 血管重构是高血压的主要病理基础。Seipin作为一个新发现的调节脂肪新生和脂滴生长的基因，其功能突变导致先天性脂肪营养不良，患者几乎没有脂肪组织，出现严重的胰岛素抵抗，极度高甘油三酯血症和严重脂肪肝，此外，患者还易发生肥厚型心肌病和高血压。我们的预实验研究发现Seipin基因敲除小鼠的血管周围脂肪组织的炎症明显增强，血管平滑肌细胞超微结构改变，出现血管重构和高血压，但其机制尚不清楚。本项目利用全身性Seipin基因敲除小鼠及血管平滑肌细胞特异性Seipin基因敲除小鼠模型，研究Seipin基因在血压调节中的作用，并探索平滑肌细胞Seipin基因及血管周围脂肪组织参与血压调节的分子机制，研究结果将为高血压的防治提供新的靶点。

Hypertension is one of most common chronic diseases, and vascular remodeling is pathological basis of hypertension. Seipin relgulates lipid storage at both adipogenesis and LD expansion levels. Mutations in Seipin are associated with the most severe form of human lipodystrophy, which characterized by nearly complete loss of adipose tissue, severe dyslipidemia, insulin resistance, and steatohepatitis. Another phenotypic features have been noted in Seipin-deficient patients are caridiomyopathy and hypertension. Our preliminary study demonstrated that Seipin knockout mice showed significantly increased inflammation in the perivascular adipose tissue, ultrastructural changes in smooth muscle cells, and increased blood pressure, but the underlying mechanism is not clear. Here, we use Seipin knockout mice and vascular smooth muscle cell specific Seipin knockout mice to investigate the role of Seipin in blood pressure regulation. We aim to dissect the molecular function of Seipin in vascular remodeling and hypertension. Our results will provide novel therapeutic strategies in combating hypertension.