| First Author | Bonta PI | Year | 2010 |
| Journal | Cardiovasc Res | Volume | 87 |
| Issue | 3 | Pages | 561-8 |
| PubMed ID | 20189954 | Mgi Jnum | J:176104 |
| Mgi Id | MGI:5288313 | Doi | 10.1093/cvr/cvq064 |
| Citation | Bonta PI, et al. (2010) Nuclear receptor Nur77 inhibits vascular outward remodelling and reduces macrophage accumulation and matrix metalloproteinase levels. Cardiovasc Res 87(3):561-8 |
| abstractText | AIMS: Structural adaptation of the vessel wall in response to sustained alterations in haemodynamic forces is known as vascular remodelling. Detailed knowledge on the mechanism underlying this vascular response is limited, and we aimed to study the function of Nur77 in smooth muscle cells (SMCs) in arterial remodelling. METHODS AND RESULTS: Carotid artery ligation in mice results in flow-induced, outward remodelling of the contralateral carotid artery, and we observed enhanced Nur77 expression during this process. Transgenic mice that express Nur77 or its dominant-negative variant, denoted as 'DeltaTA' in arterial SMCs, were exposed to carotid artery ligation, and after 4 weeks pressure-diameter relationships were measured. Structural outward remodelling is inhibited in Nur77-transgenic mice when compared with wild-type and DeltaTA-transgenic mice. The key determinants of remodelling vascular tone and macrophage accumulation were studied. No difference in contractile and relaxant responses was detected in isolated aorta, carotid, and mesenteric artery segments between transgenic and wild-type mice. SMC-specific overexpression of Nur77 in transgenic mice reduced macrophage accumulation and repressed matrix metalloproteinase (MMP)1 and MMP9 expression at early time points. MMP2 protein expression was reduced in Nur77-transgenic mice, whereas in DeltaTA-transgenic mice MMP2 expression was increased. CONCLUSION: Nur77 is induced during outward remodelling and inhibits this vascular adaptation in mice. Nur77-mediated inhibition of arterial remodelling involves a reduction in both macrophage accumulation and MMP expression levels. |
