| First Author | Xu Z | Year | 2016 |
| Journal | J Am Heart Assoc | Volume | 5 |
| Issue | 5 | PubMed ID | 27146447 |
| Mgi Jnum | J:308293 | Mgi Id | MGI:6725985 |
| Doi | 10.1161/JAHA.116.003342 | Citation | Xu Z, et al. (2016) C-C Motif Chemokine Receptor 9 Exacerbates Pressure Overload-Induced Cardiac Hypertrophy and Dysfunction. J Am Heart Assoc 5(5) |
| abstractText | BACKGROUND: Maladaptive cardiac hypertrophy is a major risk factor for heart failure, which is the leading cause of death worldwide. C-C motif chemokine receptor 9 (CCR9), a subfamily of the G protein-coupled receptor supergene family, has been highlighted as an immunologic regulator in the development and homing of immune cells and in immune-related diseases. Recently, CCR9 was found to be involved in the pathogenesis of other diseases such as cardiovascular diseases; however, the effects that CCR9 exerts in cardiac hypertrophy remain elusive. METHODS AND RESULTS: We observed significantly increased CCR9 protein levels in failing human hearts and in a mouse or cardiomyocyte hypertrophy model. In loss- and gain-of-function experiments, we found that pressure overload-induced hypertrophy was greatly attenuated by CCR9 deficiency in cardiac-specific CCR9 knockout mice, whereas CCR9 overexpression in cardiac-specific transgenic mice strikingly enhanced cardiac hypertrophy. The prohypertrophic effects of CCR9 were also tested in vitro, and a similar phenomenon was observed. Consequently, we identified a causal role for CCR9 in pathological cardiac hypertrophy. Mechanistically, we revealed a lack of difference in the expression levels of mitogen-activated protein kinases between groups, whereas the phosphorylation of AKT/protein kinase B and downstream effectors significantly decreased in CCR9 knockout mice and increased in CCR9 transgenic mice after aortic binding surgery. CONCLUSIONS: The prohypertrophic effects of CCR9 were not attributable to the mitogen-activated protein kinase signaling pathway but rather to the AKT-mammalian target of rapamycin-glycogen synthase kinase 3beta signaling cascade. |
