Healthy bone marrow transplantation into hypertriglyceridemic rats improves cardiac reparative fibrosis post-myocardial infarction

AIMS: Acute myocardial infarction (AMI) triggers an immune response characterized by a dynamic interplay between the bone marrow (BM) and the ischemic heart. However, the effect of metabolic alterations such as hypertriglyceridemia (HTG) on this inter-organ communication remains unknown. In the present study we have investigated, in a rat model of crossed-BM transplant, the impact of HTG on the BM-heart axis response to AMI under constant metabolic stress. METHODS: and results: Wistar rats (n = 56) were assigned to two groups: one fed a high-sucrose diet to induce HTG and the other fed a regular chow [normolipemic (NL)-animals]. After three weeks, all combinations of crossed-BM transplants were performed (NL-BM/NL-recipient, NL-BM/HTG-recipient, HTG-BM/NL-recipient and HTG-BM/HTG-recipient) following total body irradiation (9.5 Gy). All animals, except for NL-BM/NL-recipient group, continued on a high-sucrose diet for three weeks. Then, AMI was induced by transient coronary artery ligation and five days later, animals were sacrificed. We determined infarct size, and performed echocardiography, 1H-NMR spectroscopy and multiple molecular and histological analyses. NL-BM/HTG-recipients exhibited smaller infarcts vs the other groups and showed a resolving inflammatory response, lower lipotoxicity, higher ω3 content, increased AMPK activation and S1P-related enzymes, and reparative fibrosis in the healing scar. Although no differences were detected in LVEF post-AMI among all groups, NL-BM/HTG-recipients exhibited improved systolic and diastolic parameters. Circulating triglyceride levels were significantly reduced in NL-BM/HTG-recipients three weeks post-BM transplant, whereas, conversely, they were found to be enhanced in HTG-BM/NL-recipients developing a HTG state. Furthermore, recipients of a HTG-BM showed worsened lipid profile, liver steatosis and inflammation, higher weight gain, leptin levels and lower lipoprotein lipase, AMPK and acetyl-CoA carboxylase activity in the visceral adipose tissue vs NL-BM-recipient animals. CONCLUSIONS: Transplantation of healthy BM into HTG animals enhances the capacity to counteract myocardial injury post-AMI and restores metabolic disturbances improving overall recovery.