| First Author | Bhattarai U | Year | 2023 |
| Journal | Front Immunol | Volume | 14 |
| Pages | 1105664 | PubMed ID | 36860846 |
| Mgi Jnum | J:334442 | Mgi Id | MGI:7440651 |
| Doi | 10.3389/fimmu.2023.1105664 | Citation | Bhattarai U, et al. (2023) IL-12alpha deficiency attenuates pressure overload-induced cardiac inflammation, hypertrophy, dysfunction, and heart failure progression. Front Immunol 14:1105664 |
| abstractText | IL-12alpha plays an important role in modulating inflammatory response, fibroblast proliferation and angiogenesis through modulating macrophage polarization or T cell function, but its effect on cardiorespiratory fitness is not clear. Here, we studied the effect of IL-12alpha on cardiac inflammation, hypertrophy, dysfunction, and lung remodeling in IL-12alpha gene knockout (KO) mice in response to chronic systolic pressure overload produced by transverse aortic constriction (TAC). Our results showed that IL-12alpha KO significantly ameliorated TAC-induced left ventricular (LV) failure, as evidenced by a smaller decrease of LV ejection fraction. IL-12alpha KO also exhibited significantly attenuated TAC-induced increase of LV weight, left atrial weight, lung weight, right ventricular weight, and the ratios of them in comparison to body weight or tibial length. In addition, IL-12alpha KO showed significantly attenuated TAC-induced LV leukocyte infiltration, fibrosis, cardiomyocyte hypertrophy, and lung inflammation and remodeling (such as lung fibrosis and vessel muscularization). Moreover, IL-12alpha KO displayed significantly attenuated TAC-induced activation of CD4(+) T cells and CD8(+) T cells in the lung. Furthermore, IL-12alpha KO showed significantly suppressed accumulation and activation of pulmonary macrophages and dendritic cells. Taken together, these findings indicate that inhibition of IL-12alpha is effective in attenuating systolic overload-induced cardiac inflammation, heart failure development, promoting transition from LV failure to lung remodeling and right ventricular hypertrophy. |
