| First Author | Xu S | Year | 2011 |
| Journal | Hypertension | Volume | 58 |
| Issue | 2 | Pages | 310-6 |
| PubMed ID | 21646597 | Mgi Jnum | J:280614 |
| Mgi Id | MGI:6368922 | Doi | 10.1161/HYPERTENSIONAHA.111.172031 |
| Citation | Xu S, et al. (2011) IkappaBbeta attenuates angiotensin II-induced cardiovascular inflammation and fibrosis in mice. Hypertension 58(2):310-6 |
| abstractText | The development of cardiovascular fibrosis is associated with chronic inflammation, where activation of nuclear factor kappaB (NF-kappaB) signaling may play a critical role. NF-kappaB activation is tightly regulated by the cellular inhibitor of kappaB (IkappaB) family of proteins, such as IkappaBalpha and IkappaBbeta. IkappaBalpha and IkappaBbeta display different regulation kinetics in response to inflammatory stimulation. The present study tested the hypothesis that IkappaBalpha and IkappaBbeta may have different roles in modulating cardiovascular inflammation and fibrosis, using a model of angiotensin II infusion-induced hypertension in wild-type mice and IkappaBbeta knock-in mice, in which the IkappaBalpha gene is replaced by IkappaBbeta cDNA (AKBI). In WT mice, subcutaneous angiotensin II infusion for 7 days induced increased perivascular and interstitial collagen deposition and fibrotic lesions, associated with myocardial interstitial hemosiderin accumulation and extensive macrophage infiltration. These effects of angiotensin II were dramatically limited in AKBI mice. Replacement of IkappaBalpha with IkappaBbeta significantly attenuated angiotensin II infusion-induced expression of interleukin 1beta, interleukin 6, monocyte chemotactic protein 1, collagen I and III, fibronectin, and tissue inhibitor of metalloproteinase 1 in the hearts. Furthermore, using cultured vascular smooth muscle cells, we demonstrated that interleukin 1beta-induced NF-kappaB activation and monocyte chemotactic protein 1, vascular cell adhesion molecule 1, and tissue inhibitor of metalloproteinase 1 expressions were suppressed in the AKBI cells because of the replacement of IkappaBalpha with IkappaBbeta. These results indicate that NF-kappaB has an essential role in mediating the cardiovascular inflammatory response to angiotensin II and suggest that targeting the balance of IkappaBalpha and IkappaBbeta expression might be a novel therapeutic modality in preventing fibrosis in hypertensive cardiovascular disease. |
