肥胖是影响人类健康公认的严重问题，是心血管疾病的一个重要的危险因子，还是驱使心血管病发病率居高不下的主要原因。在众多肥胖相关性血管病变过程中，血管重构是共同的病理学基础，慢性炎症则在其发病学中发挥重要的作用。然而，血管重构中炎症反应网络调控的分子机制尚未完全阐明。我们的前期研究发现，巨噬细胞A类清道夫受体（SR-A）能够偶联MVP蛋白，并通过小凹蛋白-p38/JNK代谢途径促进炎症反应，影响细胞极性分化，并在心脑缺血性损伤等多种疾病中发挥重要作用。本项目拟在此基础上，进一步开展开展肥胖相关性血管重构的研究，通过深入探讨SR-A对血管壁和血管旁脂肪组织（PVAT）中的巨噬细胞以及血管内皮细胞活性的调控及其机制，阐明血管稳态及重构过程中巨噬细胞的炎性调控网络，揭示巨噬细胞、内皮细胞以及血管平滑肌细胞表型改变的规律，为深入认识和解决血管相关重大疾病提供理论依据，为发现新的疾病干预靶标奠定基础。

Obesity is a recognized serious problem affecting human health and also an important risk factor increasing the morbidity of cardiovascular diseases. Among the various obesity-related vascular diseases, vascular remodeling is a common pathologic basis, and chronic inflammation plays an important role in the pathogenesis. However, the molecular mechanism of inflammatory network regulation in vascular remodeling is not fully clarified. Our previous researches have found that macrophage SR-A coupled with MVP protein, promoted the inflammatory reaction by caveolin-p38/JNK pathway, influenced macropahge polarization and played an important role in ischemic injury of heart and brain and other diseases. This project plans to conduct researches on obesity-related vascular remodeling, detect the functions of SR-A in PVAT and vascular macrophages and endothelial cells, reveal the laws of phenotype change in macrophages, endothelial cells and vascular smooth muscle cells, and clarify the macrophage regulated inflammation network in vascular homeostasis and remodeling. It will provide theoretical basis for understanding and solving serious vascular diseases, and lay a foundation for finding novel targets of disease intervention.

肥胖是影响人类健康公认的严重问题，是心血管疾病的一个重要的危险因子，还是驱使心血管病发病率居高不下的主要原因。在众多肥胖相关性血管病变过程中，血管重构是共同的病理学基础，慢性炎症则在其发病学中发挥重要的作用。然而，血管重构中炎症反应网络调控的分子机制尚未完全阐明。针对这一关键的科学问题，本项目以SR-A1对巨噬细胞的活性调控为主线，深入探讨了SR-A1介导的巨噬细胞活性具有拮抗病理性血管重构、糖尿病视网膜病变以及肿瘤微环境中血管新生的作用，其分子机制与SR-A1能抑制重度糖基化终产物受体途径、激活STAT6和抑制NF-kB信号通路有关。因此，SR-A1代谢途径可能是防治炎症相关性疾病的重要新靶点。