Osteopontin modulates myocardial hypertrophy in response to chronic pressure overload in mice.
Osteopontin (OPN) expression increases in the heart during hypertrophy and heart failure. Here, we studied the role of OPN in pressure overload-induced hypertrophy and analyzed the signaling pathways involved in hypertrophy. Aortic banding (AB) was performed in a group of wild-type (WT) and OPN knockout (KO) mice to induce pressure overload. Left ventricular (LV) structural and functional remodeling was studied 1 month after AB. AB increased OPN and beta1 integrin (a receptor for OPN) protein expression in WT-AB group. Hypertrophic response as measured by increased heart weight-to-body weight ratio and myocyte cross-sectional area was significantly increased in WT-AB and KO-AB groups when compared with their respective shams. However, the increase was significantly higher in WT-AB. Re-expression of atrial natriuretic factor was only detected in WT-AB group. LV end-diastolic pressure-volume curve obtained using Langendorff perfusion analysis exhibited a leftward shift in WT-AB group, not in KO-AB. LV-developed pressures measured over a range of LV volumes were significantly increased in WT-AB, not in KO-AB mice. Increased phosphorylation of c-Jun N-terminal kinases, p38 kinase, Akt, and glycogen synthase kinase-3beta was significantly higher in WT-AB when compared with KO-AB group. Increased OPN expression may play an essential role in modulating compensatory cardiac hypertrophy in response to chronic pressure overload.
Xie
Zhonglin
Z
Department of Physiology, James H. Quillen College of Medicine, James H. Quillen Veterans Affairs Medical Center, East Tennessee State University, Johnson City, Tenn 37614, USA.
Singh
Mahipal
M
Singh
Krishna
K
D000818:Animals; D017209:Apoptosis; D006332:Cardiomegaly / Q000503:physiopathology*; D005260:Female; D005355:Fibrosis; D038362:Glycogen Synthase Kinase 3 / Q000502:physiology; D019012:Integrin beta1 / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D020929:Mitogen-Activated Protein Kinase Kinases / Q000502:physiology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D053495:Osteopontin; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt; D012795:Sialoglycoproteins / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D020257:Ventricular Remodeling / Q000502:physiology*
D019012:Integrin beta1; D011518:Proto-Oncogene Proteins; D012795:Sialoglycoproteins; C506896:Spp1 protein, mouse; D053495:Osteopontin; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; D020929:Mitogen-Activated Protein Kinase Kinases