© 2004 European Society of Cardiology
Myocardial osteopontin expression is associated with collagen fibrillogenesis in human dilated cardiomyopathy
Second Department of Internal Medicine Iwate Medical University School of Medicine, 19-1 Uchimaru, Morioka 020-8505, Iwate, Japan E-mail address: m_satoh{at}imu.ncvc.go.jp
* Corresponding author. Tel.: +81 19 651 5111; fax: +81 19 651 0401.
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Abstract |
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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.
Key Words: Collagen type I • Immunohistochemistry • In situ hybridization • Real-time polymerase chain reaction
Received July 20, 2004; Revised July 20, 2004; Accepted October 20, 2004
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