[Chlamydia pneumoniae--a new risk factor for calcific aortic stenosis?]. / Chlamydia pneumoniae--ein neuer Risikofaktor bei kalzifizierender Aortenklappenstenose?

BACKGROUND: Nonrheumatic, calcific aortic stenosis is the main heart valve disease and the main cause of heart valve replacement in the elderly. Recent studies suggest that it is based on a chronic inflammatory process. The pathogenetic mechanisms, however, are unclear. METHODS: A MEDLINE search was conducted for the phrases "chlamydia pneumoniae" and "aortic valve", and all articles published between 1966 and May 2004 were evaluated. Data presented as letter or congress abstract was also included. RESULTS: Clinical and histopathologic studies demonstrate an association of calcific aortic stenosis and cardiovascular risk factors similar to atherosclerosis. As for atherosclerosis, infection with Chlamydia (C.) pneumoniae is also discussed as a further potential risk factor for calcific aortic stenosis. Previous seroepidemiologic and pathologic studies using various detection methods yielded heterogeneous results. CONCLUSION: Thus, data suggesting a pathogenetic association of C. pneumoniae and calcific aortic stenosis should be interpreted cautiously.

Inflammatory regulation of extracellular matrix remodeling in calcific aortic valve stenosis.

BACKGROUND: Calcific aortic stenosis (AS), the most frequent heart valve disorder in developed countries, leads to the calcification and fibrous thickening of the valve. While several studies have addressed the process of valvular calcification, the molecular pathomechanisms of the extensive matrix remodeling remain unclear. Because inflammation is present in stenotic valves, we hypothesized that the proinflammatory cytokine tumor necrosis factor alpha (TNFalpha) might influence cell proliferation and regulate the expression and activation of matrix metalloproteinases (MMPs)--enzymes that are thought to be involved in calcific AS. METHODS: Immunohistochemistry for leukocytes, TNFalpha, MMP-1, and the endogenous MMP inhibitor tissue inhibitor of metalloproteinase (TIMP)-1 was performed on human stenotic (n = 19) and control (n = 8) valves. Primary cultures of human aortic valve myofibroblasts were incubated with and without TNFalpha, and cell proliferation was assessed. The expression and activation of MMP-1 were detected by Western blotting and a specific MMP-1 activity assay. RESULTS: Control valves showed scattered macrophages and low expression of TNFalpha, MMP-1, and TIMP-1. In stenotic valves, leukocyte infiltration and a strong, colocalized expression of TNFalpha and MMP-1 were present, while TIMP-1 remained unchanged. Double-label immunofluorescence localized TNFalpha mainly to macrophages. In cultured human aortic valve myofibroblasts, TNFalpha stimulated proliferation and induced a time-dependent increase in MMP-1 expression and activation, while TIMP-1 remained unchanged. CONCLUSION: The results indicate that matrix remodeling in calcific AS involves the expression and activation of MMPs. Activated leukocytes, by the secretion of TNFalpha, may stimulate valvular myofibroblasts to proliferate and express MMPs, thus regulating actively the matrix remodeling in calcific AS.