Intrarenal Delivery of Mesenchymal Stem Cells and Endothelial Progenitor Cells Attenuates Hypertensive Cardiomyopathy in Experimental Renovascular Hypertension.
Intrarenal Delivery of Mesenchymal Stem Cells and Endothelial Progenitor Cells Attenuates Hypertensive Cardiomyopathy in Experimental Renovascular Hypertension.
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DOI：
10.3727/096368914x685582
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发表时间：
2015
影响因子：
3.3
通讯作者：
Lerman LO
中科院分区：
文献类型：
--
作者：
Eirin A;Zhu XY;Ebrahimi B;Krier JD;Riester SM;van Wijnen AJ;Lerman A;Lerman LO
肾血管性高血压(RVH)会导致左心室(LV)肥厚和舒张期功能障碍，并增加心血管死亡率。肾内注射内皮祖细胞和间充质干细胞可改善猪RVH的肾功能，而MSCs强大的抗炎特性可能有助于钝化心肾轴上的炎症介质。然而，它们在减轻心脏损伤和功能障碍方面的相对有效性仍不清楚。本研究验证了内皮祖细胞和骨髓间充质干细胞移植到实验性RVH狭窄肾内的心脏保护作用具有可比性的假设。猪(每组7只)在RVH后10周进行研究，对照组在4周前未经处理或仅经一次肾内输注自体内皮祖细胞或MSCs。在体内评估心肾功能(FAST-CT)和狭窄-肾脏炎症介质释放(ELISA)，并在体外评估心肌炎症、重塑和纤维化。RVH治疗10周后，治疗组血压无明显变化，但狭窄肾小球滤过率(GFR)在RVH组减弱，RVH+EPC组改善，RVH+MSC组恢复正常。RVH+EPC组肾狭窄处单核细胞趋化蛋白1(MCP)-1的释放及其心肌表达增加，但仅在RVH+MSC组恢复正常。EPC组和MSC组RVH诱导的LV肥厚均恢复正常，而RVH+MSC组的舒张期功能(E/A值)仅恢复到正常水平。RVH+EPC组心肌纤维化和胶原沉积减少，但RVH+MSC组进一步减少。肾内注射内皮祖细胞或间充质干细胞可减轻RVH引起的心肌损伤，但骨髓间充质干细胞比内皮祖细胞更有效地恢复舒张期功能，这可能是通过更大程度地改善肾功能或减少MCP-1从狭窄的肾脏释放而实现的。这些观察提示内皮祖细胞和间充质干细胞在保护慢性实验性RVH的心肌方面具有治疗潜力。
Renovascular hypertension (RVH) leads to left ventricular (LV) hypertrophy and diastolic dysfunction, associated with increased cardiovascular mortality. Intra-renal delivery of endothelial progenitor cells (EPCs) and mesenchymal stem cells (MSCs) improves kidney function in porcine RVH, and the potent anti-inflammatory properties of MSCs may serve to blunt inflammatory mediators in the cardio-renal axis. However, their relative efficacy in attenuating cardiac injury and dysfunction remains unknown. This study tested the hypothesis that the cardio-protective effect of EPCs and MSCs delivered into the stenotic-kidney in experimental RVH are comparable. Pigs (n=7 per group) were studied after 10 weeks of RVH or control untreated or treated with a single intra-renal infusion of autologous EPCs or MSCs 4 weeks earlier. Cardiac and renal function (fast-CT) and stenotic-kidney release of inflammatory mediators (ELISA) were assessed in-vivo, and myocardial inflammation, remodeling, and fibrosis ex-vivo. After 10 weeks of RVH, blood pressure was not altered in cell-treated groups, yet stenotic-kidney glomerular filtration rate (GFR), blunted in RVH, improved in RVH+EPC and normalized in RVH+MSC. Stenotic-kidney release of monocyte chemoattractant protein (MCP)-1 and its myocardial expression were elevated in RVH+EPC, but normalized only in RVH+MSC pigs. RVH-induced LV hypertrophy was normalized in both EPC and MSC-treated pigs, while diastolic function (E/A ratio) was restored to normal levels exclusively in RVH+MSC. RVH-induced myocardial fibrosis and collagen deposition decreased in RVH+EPC, but further decreased in RVH+MSC-treated pigs. Intra-renal delivery of EPCs or MSCs attenuates RVH-induced myocardial injury, yet MSCs restore diastolic function more effectively than EPCs, possibly by greater improvement in renal function or reduction of MCP-1 release from the stenotic-kidney. These observations suggest a therapeutic potential for EPCs and MSCs in preserving the myocardium in chronic experimental RVH.