溶血磷脂酸信号对哺乳动物心肌再生的调节研究

Objective: Our previous study demonstrated that cardiac expression of lysophosphatidic acid (LPA) receptors is much higher during early postnatal period. in this study, we investigated the role of LPA signaling in mammalian heart renegeration. Methods and results: we surgically resected the left ventricular apex from 1-day-old rats. Serial histological analysis revealed progressive regeneration of the apex. At 7 day post-resection (dpr), the resection plane was characterized by a robust inflammatory response in control group while replaced by cardiomyocytes in LPA-injected group detected by morphological analysis. By 21 dpr, the most part of apical defect was replaced by cardiomyocytes and the small part was fibrosis, as detected by morphological analysis and masson staining. Left ventricular ejection fraction was assessed by echocardiography 7 and 21 days after apical resection, the results showed that the newly formed apex had normal systolic function, similar to sham operated hearts. What is more, we found LPA promoted proliferation of cardiomyocytes at 2-14 dpr. And this proliferation of LPA was completely inhibited after intraperitoneal injection of Ki16425 (LPA1/LPA3 inhibitor). Conclusions: LPA signaling promotes the restoration of the heart of neonatal rats responds to injury by cardiomyocyte proliferation, suggesting its therapeutic potential for enhancing immature heart growth in the conditions of congenital heart disease.