Role of miR-208 in cardiac fibrosis: prevention or promotion?

We read the article by Prado-Uribe et al. (1) ‘‘Role of Thyroid Hormones and mir-208 in Myocardial Remodeling in 5/6 Nephrectomized Rats’’ with great interest. The authors demonstrated that myocardial miR-208 expression was dramatically decreased but cardiac fibrosis was markedly increased in 5/6 nephrectomized rats when compared to sham rats. In thyroidectomized group, myocardial TGF-b expression was significantly reduced, whereas miR-208 was notably augmented. Treatment with thyroxine in 5/6 nephrectomized rats could induce upregulation of miR208 and downregulation of TGF-b expression. Together we may draw a conclusion that upregulation of miR-208 could prevent cardiac fibrosis in 5/6 nephrectomized rats induced by thyroxine supplementation and miR-208 may have an inverse relationship with cardiac fibrosis. However, existing evidence has shown that miR-208 has a positive correlation with cardiac fibrosis indicated by myocardial collagen volume fraction in human dilated cardiomyopathy (2). Inhibition of miR-208 expression using antagomiR208 could reduce cardiac fibrosis in response to a high-salt diet in rats (3). There was no fibrosis in miR-208 lacking mice heart compared with wild-type mice induced by thoracic aortic banding (4). Further study revealed that prevention of miR-208 could reduce endoglin and collagen I expression, and overexpression of miR-208 could obviously increase endoglin and collagen I expression in rat cardiac myoblasts induced by mechanical stretch, which may result in cardiac fibrosis (5). Moreover, cardiac fibrosis was apparently augmented resulting from overexpression of miR-208 in aorta-caval (AV) shunt rats, but distinctly attenuated after using antagomiR208. MiR208 could induce myocardial fibrosis in AV shunt rats (6). These data argued that downregulation of miR-208 may prevent cardiac fibrosis. In summary, these conflicting findings may suggest that the role of miR-208 in cardiac fibrosis is not clearly elucidated. The reason for these differences cannot be explained only by different animal models. Whether miR-208 can prevent or promote cardiac fibrosis is still to be determined. Further evidence is needed to identify the function of miR208 in cardiac fibrosis.