Intra-renal delivery of mesenchymal stem cells attenuates myocardial injury after reversal of hypertension in porcine renovascular disease.
Intra-renal delivery of mesenchymal stem cells attenuates myocardial injury after reversal of hypertension in porcine renovascular disease.
复制标题
DOI：
10.1186/scrt541
复制
发表时间：
2015-01-19
影响因子：
7.5
通讯作者：
Lerman LO
中科院分区：
文献类型：
--
作者：
Eirin A;Zhu XY;Ferguson CM;Riester SM;van Wijnen AJ;Lerman A;Lerman LO
经皮腔内肾血管成形术（PTRA）未能完全改善肾血管性高血压（RVH）患者的心脏损伤和功能障碍。间充质干细胞 (MSC) 可恢复肾功能，但其在逆转 RVH 后减轻心脏损伤的潜力尚未被探索。我们假设在 PTRA 期间补充 MSC 可以改善猪 RVH 的心脏功能和氧合，并减少心肌损伤。 RVH 16 周后对猪进行了研究，RVH 4 周前用 PTRA 治疗，有或没有辅助肾内递送 MSC（10^6 个细胞），以及对照。在体内评估心脏结构、功能（快速计算机断层扫描（CT））和心肌氧合（血氧水平依赖性磁共振成像）。离体评估心肌微血管密度（micro-CT）和心肌损伤。测量肾静脉和全身血液中炎症标志物的水平并计算其肾释放。 PTRA使血压正常化，但狭窄肾小球滤过率在RVH和RVH + PTRA中同样减弱，仅在PTRA + MSC治疗的猪中恢复正常。 PTRA 减弱了左心室重构，而 RVH + PTRA 中心肌氧合、心内膜下微血管密度和舒张功能仍然下降，但 RVH + PTRA-MSC 中则正常化。 RVH 和 RVH + PTRA 中循环异前列烷水平和肾脏炎症细胞因子释放增加，但在 RVH + PTRA-MSC 中正常化，心肌氧化应激、炎症、胶原沉积和纤维化也是如此。 PTRA 期间的肾内 MSC 递送保留了狭窄的肾功能，减少了全身氧化应激和炎症，从而在血运重建后 4 周改善了心脏功能、氧合和心肌损伤，表明辅助 MSC 递送在逆转实验性 RVH 后保留心脏功能和结构的治疗潜力。
Percutaneous transluminal renal angioplasty (PTRA) fails to fully improve cardiac injury and dysfunction in patients with renovascular hypertension (RVH). Mesenchymal stem cells (MSCs) restore renal function, but their potential for attenuating cardiac injury after reversal of RVH has not been explored. We hypothesized that replenishment of MSCs during PTRA would improve cardiac function and oxygenation, and decrease myocardial injury in porcine RVH. Pigs were studied after 16 weeks of RVH, RVH treated 4 weeks earlier with PTRA with or without adjunct intra-renal delivery of MSC (10^6 cells), and controls. Cardiac structure, function (fast-computed tomography (CT)), and myocardial oxygenation (Blood-Oxygen-Level-Dependent- magnetic resonance imaging) were assessed in-vivo. Myocardial microvascular density (micro-CT) and myocardial injury were evaluated ex-vivo. Kidney venous and systemic blood levels of inflammatory markers were measured and their renal release calculated. PTRA normalized blood pressure, yet stenotic-kidney glomerular filtration rate, similarly blunted in RVH and RVH + PTRA, normalized only in PTRA + MSC-treated pigs. PTRA attenuated left ventricular remodeling, whereas myocardial oxygenation, subendocardial microvascular density, and diastolic function remained decreased in RVH + PTRA, but normalized in RVH + PTRA-MSC. Circulating isoprostane levels and renal release of inflammatory cytokines increased in RVH and RVH + PTRA, but normalized in RVH + PTRA-MSC, as did myocardial oxidative stress, inflammation, collagen deposition, and fibrosis. Intra-renal MSC delivery during PTRA preserved stenotic-kidney function, reduced systemic oxidative stress and inflammation, and thereby improved cardiac function, oxygenation, and myocardial injury four weeks after revascularization, suggesting a therapeutic potential for adjunctive MSC delivery to preserve cardiac function and structure after reversal of experimental RVH.
登录
查看更多内容
影响因子：
4.9
作者：
Eirin A;Williams BJ;Ebrahimi B;Zhang X;Crane JA;Lerman A;Textor SC;Lerman LO
通讯作者：
Lerman LO
影响因子：
3.7
作者：
Ebrahimi B;Eirin A;Li Z;Zhu XY;Zhang X;Lerman A;Textor SC;Lerman LO
通讯作者：
Lerman LO
影响因子：
2.6
作者：
Gueant-Rodriguez, Rosa-Maria;Juilliere, Yves;Gueant, Jean-Louis
通讯作者：
Gueant, Jean-Louis
影响因子：
37.8
作者：
Chade, AR;Rodriguez-Porcel, M;Lerman, LO
通讯作者：
Lerman, LO
影响因子：
19.7
作者：
Daghini, Elena;Primak, Andrew N.;Lerman, Lilach O.
通讯作者：
Lerman, Lilach O.