Portal de Periódicos da CAPES

Vascular smooth muscle cell activation by C-reactive protein

2003; Oxford University Press; Volume: 58; Issue: 1 Linguagem: Inglês

10.1016/s0008-6363(02)00855-6

1755-3245

Yuichi Hattori, Masaru Matsumura, K. Kasai,

Atherosclerosis and Cardiovascular Diseases

Objective: C-reactive protein (CRP) is an important cardiovascular risk factor. Although the role of CRP has been implicated in atherogenesis, its direct effects on vascular cells are poorly defined. Methods: We investigated the responses to CRP in vascular smooth muscle cells (VSMC). Results: The present study shows that CRP induces parallel activation of the redox-responsive transcription factors NF-kappa B (NF-κB) and AP-1 and increases the activity of the MAP kinases (MAPKs), extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38MAPK, in VSMC. C-reactive protein increased the expression of early response genes, c-fos and c-jun and inflammatory genes, monocyte chemoattractant peptide (MCP-1) and interleukin-6 (IL-6). When VSMC were incubated with CRP, the inducible nitric oxide synthase (iNOS) promoter was activated. CRP alone was a weak inducer of NO production in VSMC as measured by determining nitrite levels, and interferon-γ alone was totally ineffective, whereas CRP plus interferon-γ was a powerful stimulus. This synergy for NO production corresponded to the results of iNOS mRNA expression analyzed by Northern blotting. The NF-κB activation caused by CRP was inhibited by 15-deoxy-12,14-prostaglandin J2 and the PPARγ activators, rosiglitazone and pioglitazone. Fluvastatin and cerivastatin also reduced the activation of NF-κB by CRP. Conclusions: CRP causes NF-κB activation which could lead to the induction of MCP-1, IL-6, and iNOS gene expression. CRP also activates the MAPK→c-Fos/cJun→AP-1 pathway. Thus, CRP may play a role in atherogenesis by activating VSMC.