Myocardial osteopontin expression is associated with collagen fibrillogenesis in human dilated cardiomyopathy.
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.


OBJECTIVE
We hypothesized that OPN could be expressed in myocardial tissues and contribute to collagen accumulation and myocardial dysfunction in human dilated cardiomyopathy (DCM).


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 > or = 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.
Satoh
Mamoru
M
Second Department of Internal Medicine, Iwate Medical University School of Medicine, 19-1 Uchimaru, Morioka 020-8505, Iwate, Japan. m_satoh@imu.ncvc.go.jp
Nakamura
Motoyuki
M
Akatsu
Tomonari
T
Shimoda
Yudai
Y
Segawa
Ikuo
I
Hiramori
Katsuhiko
K
D002311:Cardiomyopathy, Dilated / Q000378:metabolism*; D024042:Collagen Type I / Q000378:metabolism*; D024061:Collagen Type III / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D053495:Osteopontin; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012795:Sialoglycoproteins / Q000378:metabolism*
D024042:Collagen Type I; D024061:Collagen Type III; D012333:RNA, Messenger; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; D053495:Osteopontin