Abstract 4878: The Association of Osteopontin with Cardiac Fibrosis and the Responsiveness to Beta-Blockers in Patients with Heart Failure
Background and Objective: Cardiac fibrosis and remodeling might determine cardiac response to beta-blockers and mortality in patients with heart failure. Osteopontin (OPN), an adhesive protein and cytokine which can promote the activation of T lymphocyte, regulating balance between Th1 and Th2, participating in cell-induced immunologic response could cause fibrosis and remodeling after myocardial damage. Our objective was to examine the association of osteopontin with cardiac fibrosis and the response to beta-blockers in patients with heart failure.
Methods and Results: Methods and Results:
OPN-deficient mice were compared with wild-type mice before and after being treated with angiotensin II (AII). AII treatment caused cardiac hypertrophy and fibrosis in wild-type mice. OPN-deficiency could abolish the development of cardiac hypertrophy and fibrosis concomitantly while suppressing the accumulation of macrophages and expression of type II cytokines.
Endomyocardial biopsy samples were examined in 80 patients with dilated cardiomyopathy (DCM; mean age: 53.3) and compared with those without heart disease. Immuno-histchemical staining for OPN and atrial natriuretic peptide showed a positive correlation with percent fibrosis calculated in Masson’s Trichrome staining (p<0.00001).
Good responders to beta-blockers were defined as those showing a 5% improvement in left ventricular fractional shortening on echocardiography.
Genotyping of OPN G-156Del during pre-administration was performed by PCR-based methods in 120 DCM patients. OPN G156 allele was associated with the response to β-blockers (non-responder %; Del/Del 37%, Del/G + G/G 67%, p=0.002).
Conclusions: These results suggest that OPN has a pivotal role in the development of cardiac fibrosis and remodeling. As for cardiac OPN susceptibility to fibrosis and also responsiveness to beta-blockers may be genetically determined. OPN G-156Del polymorphism is an independent predictor of the response to beta-blockers in DCM patients. Such information should prove to be helpful in individualized medicine.