Increased myocardial expression of osteopontin in patients with advanced heart failure.
The expression of the adhesion protein osteopontin (OP) is associated with cardiac hypertrophy and is significantly increased after transition to heart failure in experimental animal models. We, therefore, hypothesized that OP could be upregulated in heart failure in humans. In the present study, we investigated the expression of OP in myocardial biopsies obtained from patients with heart failure due to dilated cardiomyopathy (mean LVEF=30.3+/-4.4%, mean+/-S.D., n=10, group A) compared to patients with a normal left-ventricular ejection fraction (mean LVEF=61+/-11.2%, n=9; group B). Myocardial immunoreactivity for OP was examined using two different antibodies against OP. The expression of cardiac myocyte OP was significantly upregulated in group A in comparison to group B (P<0.0001). Both groups also displayed OP immunoreactivity in non-myocytes, including vascular smooth muscle cells and cardiac fibroblasts (P=not significant). Statistical analysis revealed a significant correlation of increased OP immunoreactivity in cardiac myocytes of patients with impaired left ventricular function, assessed by hemodynamic data (LVEF, RVEF, LVESVI, LVEDVI and LVEDP, R=-0.828, -0.671, 0.751, 0.685 and 0.461, respectively; all P<0.05). Furthermore, OP expression correlated with cardiac myocyte hypertrophy (mean diameter 21.0+/-1.8 microm in group A and 16.6+/-2.1 microm in group B; P<0.0001). In conclusion, the present study indicates, that factors and/or mechanisms involved in heart failure in patients with dilated cardiomyopathy, lead to induction of OP expression in humans.
Stawowy
Philipp
P
Department of Medicine/Cardiology, German Heart Institute Berlin, Augustenburger Platz 1, D-13353, Berlin, Germany.
Blaschke
Florian
F
Pfautsch
Peter
P
Goetze
Stephan
S
Lippek
Frank
F
Wollert-Wulf
Brigitte
B
Fleck
Eckart
E
Graf
Kristof
K
D000328:Adult; D000368:Aged; D001706:Biopsy; D004452:Echocardiography; D004562:Electrocardiography; D005260:Female; D006333:Heart Failure / Q000378:metabolism*; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D053495:Osteopontin; D012720:Severity of Illness Index; D012795:Sialoglycoproteins / Q000096:biosynthesis*; D013223:Statistics as Topic; D013318:Stroke Volume / Q000502:physiology
C506895:SPP1 protein, human; D012795:Sialoglycoproteins; D053495:Osteopontin