| First Author | Francisco J | Year | 2019 |
| Journal | J Biol Chem | Volume | 294 |
| Issue | 35 | Pages | 13131-13144 |
| PubMed ID | 31311858 | Mgi Jnum | J:281342 |
| Mgi Id | MGI:6369211 | Doi | 10.1074/jbc.RA119.008970 |
| Citation | Francisco J, et al. (2019) The tumor suppressor RASSF1A modulates inflammation and injury in the reperfused murine myocardium. J Biol Chem 294(35):13131-13144 |
| abstractText | Inflammation is a central feature of cardiovascular disease, including myocardial infarction and heart failure. Reperfusion of the ischemic myocardium triggers a complex inflammatory response that can exacerbate injury and worsen heart function, as well as prevent myocardial rupture and mediate wound healing. Therefore, a more complete understanding of this process could contribute to interventions that properly balance inflammatory responses for improved outcomes. In this study, we leveraged several approaches, including global and regional ischemia/reperfusion (I/R), genetically modified mice, and primary cell culture, to investigate the cell type-specific function of the tumor suppressor Ras association domain family member 1 isoform A (RASSF1A) in cardiac inflammation. Our results revealed that genetic inhibition of RASSF1A in cardiomyocytes affords cardioprotection, whereas myeloid-specific deletion of RASSF1A exacerbates inflammation and injury caused by I/R in mice. Cell-based studies revealed that RASSF1A negatively regulates NF-kappaB and thereby attenuates inflammatory cytokine expression. These findings indicate that myeloid RASSF1A antagonizes I/R-induced myocardial inflammation and suggest that RASSF1A may be a promising target in immunomodulatory therapy for the management of acute heart injury. |
