| First Author | Miyagawa K | Year | 2017 |
| Journal | Biochem Biophys Res Commun | Volume | 487 |
| Issue | 3 | Pages | 587-593 |
| PubMed ID | 28433630 | Mgi Jnum | J:251298 |
| Mgi Id | MGI:6101527 | Doi | 10.1016/j.bbrc.2017.04.096 |
| Citation | Miyagawa K, et al. (2017) Loss of MURC/Cavin-4 induces JNK and MMP-9 activity enhancement in vascular smooth muscle cells and exacerbates abdominal aortic aneurysm. Biochem Biophys Res Commun 487(3):587-593 |
| abstractText | Abdominal aortic aneurysm (AAA) is relatively common in elderly patients with atherosclerosis. MURC (muscle-restricted coiled-coil protein)/Cavin-4 modulating the caveolae function of muscle cells is expressed in cardiomyocytes, skeletal muscle cells and smooth muscle cells. Here, we show a novel functional role of MURC/Cavin-4 in vascular smooth muscle cells (VSMCs) and AAA development. Both wild-type (WT) and MURC/Cavin-4 knockout (MURC(-/-)) mice subjected to periaortic application of CaCl2 developed AAAs. Six weeks after CaCl2 treatment, internal and external aortic diameters were significantly increased in MURC(-/-) AAAs compared with WT AAAs, which were accompanied by advanced fibrosis in the tunica media of MURC(-/-) AAAs. The activity of JNK and matrix metalloproteinase (MMP) -2 and -9 were increased in MURC(-/-) AAAs compared with WT AAAs at 5 days after CaCl2 treatment. At 6 weeks after CaCl2 treatment, MURC(-/-) AAAs exhibited attenuated JNK activity compared with WT AAAs. There was no difference in the activity of MMP-2 or -9 between saline and CaCl2 treatments. In MURC/Cavin-4-knockdown VSMCs, TNFalpha-induced activity of JNK and MMP-9 was enhanced compared with control VSMCs. Furthermore, WT, MURC(-/-), apolipoprotein E(-/-) (ApoE(-/-)), and MURC/Cavin-4 and ApoE double-knockout (MURC(-/-)ApoE(-/-)) mice were subjected to angiotensin II (Ang II) infusion. In both ApoE(-/-) and MURC(-/-)ApoE(-/-) mice infused for 4 weeks with Ang II, AAAs were promoted. The internal aortic diameter was significantly increased in Ang II-infused MURC(-/-)ApoE(-/-) mice compared with Ang II-infused ApoE(-/-) mice. In MURC/Cavin-4-knockdown VSMCs, Ang II-induced activity of JNK and MMP-9 was enhanced compared with control VSMCs. Our results suggest that MURC/Cavin-4 in VSMCs modulates AAA progression at the early stage via the activation of JNK and MMP-9. MURC/Cavin-4 is a potential therapeutic target against AAA progression. |
