title: Osteopontin modulates myocardial hypertrophy in response to chronic pressure overload in mice.
abstract: 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.
authors.affiliation: 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.
authors.forename: Zhonglin
authors.initials: Z
authors.lastname: Xie
authors.forename: Mahipal
authors.initials: M
authors.lastname: Singh
authors.forename: Krishna
authors.initials: K
authors.lastname: Singh
mesh_terms: 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*
chemical_list: 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