| First Author | Martinod K | Year | 2017 |
| Journal | J Exp Med | Volume | 214 |
| Issue | 2 | Pages | 439-458 |
| PubMed ID | 28031479 | Mgi Jnum | J:240430 |
| Mgi Id | MGI:5883387 | Doi | 10.1084/jem.20160530 |
| Citation | Martinod K, et al. (2017) Peptidylarginine deiminase 4 promotes age-related organ fibrosis. J Exp Med 214(2):439-458 |
| abstractText | Aging promotes inflammation, a process contributing to fibrosis and decline in organ function. The release of neutrophil extracellular traps (NETs [NETosis]), orchestrated by peptidylarginine deiminase 4 (PAD4), damages organs in acute inflammatory models. We determined that NETosis is more prevalent in aged mice and investigated the role of PAD4/NETs in age-related organ fibrosis. Reduction in fibrosis was seen in the hearts and lungs of aged PAD4-/- mice compared with wild-type (WT) mice. An increase in left ventricular interstitial collagen deposition and a decline in systolic and diastolic function were present only in WT mice, and not in PAD4-/- mice. In an experimental model of cardiac fibrosis, cardiac pressure overload induced NETosis and significant platelet recruitment in WT but not PAD4-/- myocardium. DNase 1 was given to assess the effects of extracellular chromatin. PAD4 deficiency or DNase 1 similarly protected hearts from fibrosis. We propose a role for NETs in cardiac fibrosis and conclude that PAD4 regulates age-related organ fibrosis and dysfunction. |
