Beta3 integrin deficiency promotes cardiac hypertrophy and inflammation.
Cardiac hypertrophy commonly develops in response to pressure overload and is associated with increased mortality. Mechanical stress in the heart can result in the activation of transmembrane integrin alphabeta heterodimers that are expressed in cardiomyocytes. Once activated, integrins stimulate focal adhesion kinase, Grb2, c-src, and other signaling molecules to promote cardiomyocyte growth and gene expression. Mechanical stress can also promote cardiac inflammation that may be mediated, in part, by the activation of integrins expressed in blood-borne cells. To address the role of one integrin, beta(3), in the pathogenesis of cardiac hypertrophy, beta(3)(-/-) mice were examined. beta(3)(-/-) Mice developed moderate spontaneous cardiac hypertrophy associated with systolic and diastolic dysfunction, and these abnormalities were exacerbated by transverse aortic constriction. In addition, beta(3)(-/-) mice developed mild cardiac inflammation with infiltrating macrophages at baseline that was markedly worsened by pressure overload. Bone marrow transplantation experiments showed that blood-borne cells were at least partially responsible for the cardiac hypertrophy and inflammation observed in beta(3)(-/-) mice. These results suggest that alpha(v)beta(3) expression in bone marrow has a generalized suppressive effect on cardiac inflammation.
Ren
Jie
J
Center for Cardiovascular Research, Washington University School of Medicine, St. Louis, MO 63110, USA.
Avery
Joan
J
Zhao
Haibo
H
Schneider
Jochen G
JG
Ross
F Patrick
FP
Muslin
Anthony J
AJ
D000818:Animals; D001853:Bone Marrow / Q000378:metabolism* / Q000473:pathology; D016026:Bone Marrow Transplantation; D006332:Cardiomegaly / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000503:physiopathology; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D039482:Integrin alpha5 / Q000378:metabolism; D039661:Integrin beta3 / Q000235:genetics; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009205:Myocarditis / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000503:physiopathology; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D011494:Protein Kinases / Q000096:biosynthesis
D039482:Integrin alpha5; D039661:Integrin beta3; D011494:Protein Kinases