衰老诱导的管周脂肪干/祖细胞分化异常加剧血管损伤的机制研究

血管壁特别是血管外膜存在大量原位干/祖细胞，可以定向分化并参与血管重塑过程。近期研究发现与外膜紧密相邻的血管外周脂肪组织（PVAT）作为一新的管壁成分在血管功能中起重要作用，然而是否存在干细胞尚未见报道，我们前期研究发现PVAT表达Sca1等干细胞标志，提示PVAT存在原位干细胞（PVASCs），且其分化受衰老影响。因此我们假设：管周PVASCs通过定向分化为不同的血管细胞参与血管损伤过程，衰老是影响PVASCs分化并加剧血管损伤后重塑的重要因素。基于此本项目将研究：1）鉴定管周PVASCs的分子表型及分化多潜能；2）研究衰老对PVASCs增殖、迁移及分化多潜能的影响3）阐明衰老参与PVASCs分化调控的分子机制；4）证实转录因子PPARγ在分化调控中的作用机制，阐明其对血管重塑过程的调控作用。本研究将首次证实PVASCs的存在及生物学功能，并为防治衰老相关血管疾病提供理论依据。

Mesenchymal stem cells or progentior cells resided in the vascular wall contribute to vascular injury. Perivascular adipose tissue (PVAT) regulates blood vessel structure and function in health and disease. However, the resident stem cells in the PVAT (PVASCs) are poorly understood in the vascular disease. This project aim to characterize the resistant PVAT-derived MSCs (PVASCs) and investigate their fate in the vascular remodeling process during aging. our prelimary study have showed a population of Sca1 positive cells in the PVAT and the differentiational potential was altered during aging. Based on these, we will furhter explored: 1) Characterizes the resistant stem cells in the PVAT; 2) The effects of aging on the PVASCs differentiation capacity; 3) The molecular mechanism of aging-induced alteration of PVASCs differentiation; 4) Demonstrate the role of transcription factor PPARγ in the differentiation of PVASCs. Our finding for the first time characterizes the resistant stem cells in the PVAT, and provides potential therapic target for aging-related vascular diseases.