| First Author | Civitarese RA | Year | 2016 |
| Journal | Am J Physiol Heart Circ Physiol | Volume | 311 |
| Issue | 1 | Pages | H96-H106 |
| PubMed ID | 27199132 | Mgi Jnum | J:234774 |
| Mgi Id | MGI:5790869 | Doi | 10.1152/ajpheart.00918.2015 |
| Citation | Civitarese RA, et al. (2016) The alpha11 integrin mediates fibroblast-extracellular matrix-cardiomyocyte interactions in health and disease. Am J Physiol Heart Circ Physiol 311(1):H96-H106 |
| abstractText | Excessive cardiac interstitial fibrosis impairs normal cardiac function. We have shown that the alpha11beta1 (alpha11) integrin mediates fibrotic responses to glycated collagen in rat myocardium by a pathway involving transforming growth factor-beta. Little is known of the role of the alpha11 integrin in the developing mammalian heart. Therefore, we examined the impact of deletion of the alpha11 integrin in wild-type mice and in mice treated with streptozotocin (STZ) to elucidate the role of the alpha11 integrin in normal cardiac homeostasis and in the pathogenesis of diabetes-related fibrosis. As anticipated, cardiac fibrosis was reduced in alpha11 integrin knockout mice (alpha11(-/-); C57BL/6 background) treated with STZ compared with STZ-treated wild-type mice (P < 0.05). Unexpectedly, diastolic function was impaired in both vehicle and STZ-treated alpha11(-/-) mice, as shown by the decreased minimum rate of pressure change and prolonged time constant of relaxation in association with increased end-diastolic pressure (all P < 0.05 compared with wild-type mice). Accordingly, we examined the phenotype of untreated alpha11(-/-) mice, which demonstrated a reduced cardiomyocyte cross-sectional cell area and myofibril thickness (all P < 0.05 compared with wild-type mice) and impaired myofibril arrangement. Immunostaining for desmin and connexin 43 showed abnormal intermediate filament organization at intercalated disks and impaired gap-junction development. Overall, deletion of the alpha11 integrin attenuates cardiac fibrosis in the mammalian mouse heart and reduces ECM formation as a result of diabetes. Furthermore, alpha11 integrin deletion impairs cardiac function and alters cardiomyocyte morphology. These findings shed further light on the poorly understood interaction between the fibroblast-cardiomyocyte and the ECM. |
