Rowe Gabrielle, Kelm Natia Q, Beare Jason E, Tracy Evan, Yuan Fangping, LeBlanc Amanda J
Cardiovascular Innovation Institute, University of Louisville, Louisville, KY 40292, USA.
Department of Physiology, University of Louisville, Louisville, KY 40292, USA.
Aging (Albany NY). 2019 Jul 11;11(13):4561-4578. doi: 10.18632/aging.102069.
Our past study showed that a single tail vein injection of adipose-derived stromal vascular fraction (SVF) into old rats was associated with improved dobutamine-mediated coronary flow reserve. We hypothesize that i.v. injection of SVF improves coronary microvascular function in aged rats via alterations in beta adrenergic microvascular signaling. Female Fischer-344 rats aged young (3 months, n=32) and old (24 months, n=30) were utilized, along with two cell therapies intravenously injected in old rats four weeks prior to sacrifice: 1x10 green fluorescent protein (GFP+) SVF cells (O+SVF, n=21), and 5x10 GFP+ bone-marrow mesenchymal stromal cells (O+BM, n=6), both harvested from young donors. Cardiac ultrasound and pressure-volume measurements were obtained, and coronary arterioles were isolated from each group for microvessel reactivity studies and immunofluorescence staining. Coronary flow reserve decreased with advancing age, but this effect was rescued by the SVF treatment in the O+SVF group. Echocardiography showed an age-related diastolic dysfunction that was improved with SVF to a greater extent than with BM treatment. Coronary arterioles isolated from SVF-treated rats showed amelioration of the age-related decrease in vasodilation to a non-selective β-AR agonist. I.v. injected SVF cells improved β-adrenergic receptor-dependent coronary flow and microvascular function in a model of advanced age.
我们过去的研究表明，向老年大鼠单次尾静脉注射脂肪来源的基质血管成分（SVF）与多巴酚丁胺介导的冠状动脉血流储备改善有关。我们假设静脉注射SVF可通过改变β肾上腺素能微血管信号来改善老年大鼠的冠状动脉微血管功能。使用了年轻（3个月，n = 32）和老年（24个月，n = 30）的雌性Fischer-344大鼠，并且在处死前四周对老年大鼠静脉注射两种细胞疗法：1×10绿色荧光蛋白（GFP +）SVF细胞（O + SVF，n = 21）和5×10 GFP +骨髓间充质基质细胞（O + BM，n = 6），两者均从年轻供体中收获。进行了心脏超声和压力-容积测量，并从每组中分离出冠状动脉小动脉用于微血管反应性研究和免疫荧光染色。冠状动脉血流储备随年龄增长而降低，但O + SVF组中的SVF治疗挽救了这种效应。超声心动图显示与年龄相关的舒张功能障碍，SVF对其改善程度大于BM治疗。从接受SVF治疗的大鼠中分离出的冠状动脉小动脉显示，对非选择性β-AR激动剂的血管舒张的年龄相关下降有所改善。在老年模型中，静脉注射SVF细胞改善了β肾上腺素能受体依赖性冠状动脉血流和微血管功能。
