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10.3727/096368914X685582

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suck abstract from ncbi


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pmid25420012      Cell+Transplant 2015 ; 24 (10): 2041-53
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  • Intra-renal delivery of mesenchymal stem cells and endothelial progenitor cells attenuates hypertensive cardiomyopathy in experimental renovascular hypertension #MMPMID25420012
  • Eirin A; Zhu XY; Ebrahimi B; Krier JD; Riester SM; van Wijnen AJ; Lerman A; Lerman LO
  • Cell Transplant 2015[]; 24 (10): 2041-53 PMID25420012show ga
  • Background: 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. Methods: 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. Results: 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. Conclusions: 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.
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