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Myocardial osteopontin expression is associated with collagen fibrillogenesis in human dilated cardiomyopathy
Author(s) -
Satoh Mamoru,
Nakamura Motoyuki,
Akatsu Tomonari,
Shimoda Yudai,
Segawa Ikuo,
Hiramori Katsuhiko
Publication year - 2005
Publication title -
european journal of heart failure
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.149
H-Index - 133
eISSN - 1879-0844
pISSN - 1388-9842
DOI - 10.1016/j.ejheart.2004.10.019
Subject(s) - osteopontin , ejection fraction , dilated cardiomyopathy , in situ hybridization , medicine , extracellular matrix , immunostaining , messenger rna , heart failure , fibrillogenesis , biopsy , cardiomyopathy , immunohistochemistry , pathology , cardiology , biology , gene , microbiology and biotechnology , in vitro , biochemistry
Background Osteopontin (OPN), an extracellular matrix (ECM) protein, plays an important role in myocardial remodeling by promoting collagen synthesis and accumulation in experimental animal models. Aims We hypothesized that OPN could be expressed in myocardial tissues and contribute to collagen accumulation and myocardial dysfunction in human dilated cardiomyopathy (DCM). Methods and results Endomyocardial biopsy tissues were obtained from 51 patients with DCM and 15 controls by right ventricular endomyocardial biopsy. OPN, collagen types I (Col I) and III (Col III) mRNA levels were measured by real‐time reverse transcriptase polymerase chain reaction (RT–PCR). The cellular source of OPN was analyzed using immunohistochemistry and in situ hybridization. Myocardial collagen volume fraction (CVF) was determined by digital planimetry. OPN, Col I and Col III mRNA levels were higher in DCM patients than in controls ( P <0.01). OPN mRNA levels were positively correlated with Col I levels and CVF in DCM patients (OPN vs. Col I: r =0.60, P <0.01; OPN vs. CVF: r =0.52, P <0.001). Immunostaining of OPN was present in cardiomyocytes from DCM patients. In situ hybridization identified cardiomyocytes as the major source of OPN mRNA transcription in DCM patients. OPN and Col I mRNA levels were highly expressed in the DCM subgroup with large left ventricular (LV) end‐systolic diameter (LVESD≥54.5 mm) or low LV ejection fraction (LVEF<29.5%). There was a weak positive correlation between OPN mRNA levels and LV end‐systolic diameter ( r =0.39, P <0.01). Levels of OPN mRNA were also negatively correlated with LV ejection fraction ( r =−0.43, P <0.01). Conclusions These results suggest that OPN may play a pivotal role in the development of Col‐I‐induced cardiac fibrosis and dysfunction in human DCM.