Perivascular adipose tissue-derived stromal cells contribute to vascular remodeling during aging
Perivascular adipose tissue-derived stromal cells contribute to vascular remodeling during aging
复制标题
血管周围脂肪组织来源的基质细胞有助于衰老过程中的血管重塑
DOI：
10.1111/acel.12969
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发表时间：
2019-08-01
期刊：
影响因子：
7.8
通讯作者：
Gao, Ping-Jin
中科院分区：
文献类型：
--
作者：
Pan, Xiao-Xi;Ruan, Cheng-Chao;Gao, Ping-Jin
衰老是血管疾病的独立危险因素。血管周围脂肪组织(PVAT)是血管系统的活性成分，在衰老过程中会导致血管功能障碍。识别潜在的细胞类型及其在衰老过程中的变化可能为与衰老相关的血管疾病的临床相关性提供有意义的见解。在这里，我们利用单细胞RNA序列来描述PVAT中驻留的基质细胞(PVASCs)，并在年轻和老年PVASCs之间鉴定不同的簇状细胞。生物信息学分析显示，随着年龄的增长，PVASCs的内皮和棕色成脂分化能力降低，这是血管周围输送到结扎的颈动脉后导致新生内膜增生的原因之一。从机制上讲，体外和体内研究都表明，衰老诱导的过氧化体增殖物激活受体-γ共激活因子-1α(PGC1α)的缺失是衰老PVASCs棕色成脂分化减少的关键调节因素。我们进一步证明了人PVASCs(HPVASCs)的存在和PGC1α的过表达改善了hPVASC传递诱导的血管重构。我们的研究结果强调，PVASCs的分化能力随着年龄的增长而改变，在衰老的PVASCs中，PGC1α的缺失通过减少棕色成脂分化而参与血管重建。
Aging is an independent risk factor for vascular diseases. Perivascular adipose tissue (PVAT), an active component of the vasculature, contributes to vascular dysfunction during aging. Identification of underlying cell types and their changes during aging may provide meaningful insights regarding the clinical relevance of aging-related vascular diseases. Here, we take advantage of single-cell RNA sequence to characterize the resident stromal cells in the PVAT (PVASCs) and identified different clusters between young and aged PVASCs. Bioinformatics analysis revealed decreased endothelial and brown adipogenic differentiation capacities of PVASCs during aging, which contributed to neointimal hyperplasia after perivascular delivery to ligated carotid arteries. Mechanistically, in vitro and in vivo studies both suggested that aging-induced loss of peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC1 alpha) was a key regulator of decreased brown adipogenic differentiation in senescent PVASCs. We further demonstrated the existence of human PVASCs (hPVASCs) and overexpression of PGC1 alpha improved hPVASC delivery-induced vascular remodeling. Our finding emphasizes that differentiation capacities of PVASCs alter during aging and loss of PGC1 alpha in aged PVASCs contributes to vascular remodeling via decreased brown adipogenic differentiation.