Modulation of integrins and integrin signaling molecules in the pressure-loaded murine ventricle.
Integrins are heterodimeric cell-surface receptors that link the extracellular matrix and the intracellular cytoskeleton and function as mechanotransducers. Signaling through integrins is important for cell growth, migration, and survival. Extracellular matrix is altered in the myocardium during hypertrophic induction and the transition to heart failure. The role of integrins in this process is poorly understood. Recently, integrin subunits have been identified that are dominantly expressed in striated muscle. We tested the hypothesis that since integrins are mechanotransducers, their expression and signaling would be modulated with murine left ventricular hemodynamic loading. The acute and chronic effects of pressure overload on changes in the expression of integrins, as well as related integrin-mediated signaling events were studied. Acute pressure loading increased phosphorylation of focal adhesion kinase, p42 and p44 extracellular signal-regulated kinase. Chronic loading: (1) increased expression of alpha1, alpha5, and beta1 integrin transcripts and (2) increased protein expression of integrin subunits which are dominantly expressed in striated muscle (alpha7 and beta1D) both by western blotting and immunofluorescent microscopy. These results show that adaptive responses of the myocardium to pressure overload include acute modulation of integrin-related signaling molecules and more chronic changes effect expression of integrin subunits, including ones dominantly expressed in muscle.
Babbitt
Christopher J
CJ
Department of Physiology, and The Cardiovascular Research Laboratories, The David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Shai
Shaw-Yung
SY
Harpf
Alice E
AE
Pham
Can G
CG
Ross
Robert S
RS
D000818:Animals; D001011:Aorta / Q000601:surgery; D009320:Atrial Natriuretic Factor / Q000235:genetics / Q000378:metabolism; D015152:Blotting, Northern; D015153:Blotting, Western; D006332:Cardiomegaly / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D003251:Constriction, Pathologic / Q000150:complications; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D015870:Gene Expression; D006352:Heart Ventricles / Q000378:metabolism* / Q000473:pathology; D066298:In Vitro Techniques; D016023:Integrins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010766:Phosphorylation; D011312:Pressure; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction
D016023:Integrins; D009320:Atrial Natriuretic Factor; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496051:Ptk2 protein, mouse; D020928:Mitogen-Activated Protein Kinases