Deletion of the α8 Integrin Gene Does Not Protect Mice From Myocardial Fibrosis in DOCA Hypertension

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In the heart, the α8 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 α8 integrin-mediated cell-matrix interactions add to cardiac fibrotic alterations during hypertension.


Desoxycorticosterone-acetate (DOCA)-salt hypertension was induced in mice homozygous for a deletion of the α8 integrin chain and wild-type mice. Histological and immunohistochemical evaluations were performed in heart tissue.


Blood pressure was slightly higher in DOCA-treated α8 integrin-deficient mice compared to DOCA-treated wild types. Expression of α8 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 α8 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 α8 integrin-deficient and DOCA-treated wild-type mice. Despite of a comparable degree of fibrosis in both groups, α-smooth-muscle actin and discoidin domain receptor 2 (DDR2)-positive myofibroblasts were only detected in wild-type DOCA-treated mice, not in DOCA-treated α8 integrin-deficient mice.


The results show that lack of α8 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 α8 integrin expression in the myocardium in hypertension.

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