骨桥蛋白通过促血管新生调节心肌梗死后左室重构

目的 观察骨桥蛋白(OPN)转基因小鼠(OPN^-/-)心肌梗死后心肌血管新生能力及其与左室重构的关系。方法 采用OPN^-/-小鼠体外心肌内皮细胞管结构形成、体内心肌Matrigel植入及心肌梗死3种模型，以野生型小鼠(WT)作为对照。结果 体外培养的OPN^-/-小鼠心肌血管内皮细胞在Matrigel的管结构生成显著减弱，可溶性OPN能明显改善OPN^-/-内皮细胞的管结构生成能力。在OPN^-/-小鼠心肌Matrigel植入模型，毛细血管样结构生成的体积明显降低。OPN^-/-小鼠心肌梗死后7和14d，梗死区毛细血管密度和小动脉密度均明显降低。且在梗死后7～14d，OPN^-/-小鼠小动脉的去血管化速率显著加快。OPN^-/-小鼠心肌梗死后，左室扩大及梗死区室壁变薄均较对照组显著。结论 OPN的促血管新生机制在心肌梗死后左室重构的调节中起重要作用。

Regulation of osteopontin on left ventricular remodeling by promoting angiogenesis after myocardial infarction

Objective Osteopontin (OPN) overexpressed after myocardial infarction has an important role in regulating left ventricular remodeling. We hypothesize that deficiency of OPN impairs myocardial angiogenesis after myocardial infarction, which is responsible for early left ventricular remodeling.Methods Three experimental models, in vitro cardiac endothelial cell Matrigel tube formation, in vivo myocardial Matrigel angiogenesis, and angiogenesis in myocardial infarction were used to investigate the angiogenesis in OPN knockout (OPN -/-) and wild-type (WT) mice. Results For OPN -/- mice, in vitro tube formation was markedly decreased and three with treatment of soluble OPN protein increased significantly the total tubal length. The volume of capillary-like structures was markedly decreased after implantation of Matrigel into the myocardium. Both capillary and arteriolar density decreased significantly in the infarcted region at day 7 and 14 after myocardial infarction in OPN -/- mice. Furthermore, the devascularization rate for arterioles was significantly faster in OPN -/- than WT mice. Left ventricular enlargement was increased and infarct thickness decreased on day 7 and day 14 after myocardial infaction in OPN -/- mice compared with WT mice.Conclusion The pro-angiogenic response with OPN plays an important role in strengthening left ventricular remodeling after myocardial infarction.