Division of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI.
Division of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI
J Am Heart Assoc. 2018 Jun 12;7(12):e008344. doi: 10.1161/JAHA.117.008344.
Mesenchymal stem cell-derived extracellular vesicles (EVs) are believed to be cardioprotective in myocardial infarct. The objective of this study was to examine the effects of human mesenchymal cell-derived EV injection on cardiac function, myocardial blood flow, and vessel density in the setting of chronic myocardial ischemia.
Twenty-three Yorkshire swine underwent placement of an ameroid constrictor on their left circumflex artery. Two weeks later, the animals were split into 2 groups: the control group (CON; n=7) and the EV myocardial injection group (MVM; n=10). The MVM group underwent myocardial injection of 50 μg of EVs in 2 mL 0.9% saline into the ischemic myocardium. Five weeks later, the pigs underwent a harvest procedure, and the left ventricular myocardium was analyzed. Absolute blood flow and the ischemic/nonischemic myocardial perfusion ratio were increased in the ischemic myocardium in the MVM group compared with the CON group. Pigs in the MVM group had increased capillary and arteriolar density in the ischemic myocardial tissue compared with CON pigs. There was an increase in expression of the phospho-mitogen-activated protein kinase/mitogen-activated protein kinase ratio, the phospho-endothelial nitric oxide synthase/endothelial nitric oxide synthase ratio, and total protein kinase B in the MVM group compared with CON. There was an increase in cardiac output and stroke volume in the MVM group compared with CON.
In the setting of chronic myocardial ischemia, myocardial injection of human mesenchymal cell-derived EVs increases blood flow to ischemic myocardial tissue by induction of capillary and arteriolar growth via activation of the protein kinase B/endothelial nitric oxide synthase and mitogen-activated protein kinase signaling pathways resulting in increased cardiac output and stroke volume.
间充质干细胞衍生的细胞外囊泡（EVs）被认为在心肌梗死中有心脏保护作用。本研究的目的是研究人骨髓间充质细胞衍生的 EV 注射对慢性心肌缺血模型中心脏功能、心肌血流和血管密度的影响。
23 头约克夏猪接受了左回旋支动脉的缩窄环放置术。2 周后，将动物分为 2 组：对照组（CON；n=7）和 EV 心肌注射组（MVM；n=10）。MVM 组将 50μg 的 EV 用 0.9%生理盐水 2mL 注射到缺血心肌。5 周后，进行收获手术，分析左心室心肌。与 CON 组相比，MVM 组缺血心肌的绝对血流量和缺血/非缺血心肌灌注比值增加。与 CON 猪相比，MVM 组缺血心肌组织的毛细血管和小动脉密度增加。与 CON 组相比，MVM 组磷酸化丝裂原激活蛋白激酶/丝裂原激活蛋白激酶比值、磷酸化内皮型一氧化氮合酶/内皮型一氧化氮合酶比值和总蛋白激酶 B 的表达增加。与 CON 组相比，MVM 组的心输出量和每搏量增加。
在慢性心肌缺血的情况下，通过激活蛋白激酶 B/内皮型一氧化氮合酶和丝裂原激活蛋白激酶信号通路诱导毛细血管和小动脉生长，人骨髓间充质细胞衍生的 EV 心肌注射增加缺血心肌组织的血流，从而增加心输出量和每搏量。
