| First Author | Kan X | Year | 2016 |
| Journal | Cardiovasc Res | Volume | 109 |
| Issue | 2 | Pages | 249-59 |
| PubMed ID | 26614777 | Mgi Jnum | J:252574 |
| Mgi Id | MGI:6107317 | Doi | 10.1093/cvr/cvv255 |
| Citation | Kan X, et al. (2016) Deficiency of IL-12p35 improves cardiac repair after myocardial infarction by promoting angiogenesis. Cardiovasc Res 109(2):249-59 |
| abstractText | AIMS: IL-12p35 is a pro-inflammatory cytokine that participates in a variety of inflammatory diseases. This study aimed to determine whether IL-12 regulates cardiac injury and repair following acute myocardial infarction (AMI) and investigate the underlying mechanisms. METHODS AND RESULTS: Mice with AMI showed a marked increase in IL-12p35 expression of ischaemic cardiac tissues. IL-12 was mainly produced by CD11b(+) monocytes. Cardiac functions were significantly improved in IL-12p35 knockout (p35-KO) mice compared with wild-type (WT) littermates in response to AMI. IL-12p35 deficiency attenuated the infarct scar and hypertrophy compared with WT mice. RNA transcriptome sequencing and quantitative RT-PCR analysis of CD11b(+) monocytes isolated from WT and p35-KO ischaemic hearts revealed a distinct transcriptional profile in p35-KO CD11b(+) monocytes, displaying pro-angiogenesis and anti-inflammation properties. Angiogenesis was enhanced in p35-KO mice with AMI and hindlimb ischaemia. Moreover, tube formation assay and Matrigel plug analysis demonstrated that IL-12 inhibition of angiogenesis was dependent on monocytes. IL-12p35 deficiency inhibited inflammation by reducing chemokine production and monocyte infiltration into the heart. Finally, administration of an IL-12p35-neutralizing antibody limited AMI-induced inflammatory cell infiltration into the heart and improved angiogenesis and cardiac function. CONCLUSIONS: Deficiency of IL-12p35 limited AMI-induced cardiac injury by promoting pro-angiogenesis and anti-inflammatory functions of monocytes. |
