Deletion of the alpha8 integrin gene does not protect mice from myocardial fibrosis in DOCA hypertension.
BACKGROUND
In the heart, the alpha8 integrin chain is expressed in fibroblasts and vascular smooth-muscle cells but its functional role in the myocardium is unknown. Integrins can contribute to tissue fibrosis in several organs. We tested the hypothesis that alpha8 integrin-mediated cell-matrix interactions add to cardiac fibrotic alterations during hypertension.


METHODS
Desoxycorticosterone-acetate (DOCA)-salt hypertension was induced in mice homozygous for a deletion of the alpha8 integrin chain and wild-type mice. Histological and immunohistochemical evaluations were performed in heart tissue.


RESULTS
Blood pressure was slightly higher in DOCA-treated alpha8 integrin-deficient mice compared to DOCA-treated wild types. Expression of alpha8 integrin and its ligands fibronectin and osteopontin was increased in the hearts of DOCA-treated wild types compared to salt-loaded controls. However, relative left ventricular weights did not differ between DOCA-treated wild types and alpha8 integrin-deficient mice. Moreover, expansion of collagen I immunoreactivity and cell proliferation was similar in both groups. The number of osteopontin-positive cells was not different in DOCA-treated alpha8 integrin-deficient and DOCA-treated wild-type mice. Despite of a comparable degree of fibrosis in both groups, alpha-smooth-muscle actin and discoidin domain receptor 2 (DDR2)-positive myofibroblasts were only detected in wild-type DOCA-treated mice, not in DOCA-treated alpha8 integrin-deficient mice.


CONCLUSIONS
The results show that lack of alpha8 integrin does not reduce fibrotic changes in the hearts of DOCA-salt hypertensive mice. Our findings do not argue for a profibrotic effect of an increased alpha8 integrin expression in the myocardium in hypertension.
Hartner
Andrea
A
Department of Pediatric and Adolescent Medicine, University of Erlangen-Nürnberg, Erlangen, Germany. andrea.hartner@uk-erlangen.de
Cordasic
Nada
N
Rascher
Wolfgang
W
Hilgers
Karl F
KF
D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D004247:DNA / Q000235:genetics*; D003900:Desoxycorticosterone / Q000633:toxicity; D004195:Disease Models, Animal; D004719:Endomyocardial Fibrosis / Q000097:blood / Q000209:etiology / Q000235:genetics*; D015870:Gene Expression; D006973:Hypertension / Q000097:blood / Q000139:chemically induced / Q000150:complications*; D007150:Immunohistochemistry; D039001:Integrin alpha Chains / Q000097:blood / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017384:Sequence Deletion
D039001:Integrin alpha Chains; C093856:integrin alpha8; D003900:Desoxycorticosterone; D004247:DNA