Periostin deficiency in mice impaired cardiac healing after acute myocardial infarction, resulting in cardiac rupture due to reduced myocardial stiffness and impaired collagen fibril formation.
Acute myocardial infarction (AMI) is a common and lethal heart disease, and the recruitment of fibroblastic cells to the infarct region is essential for the cardiac healing process. Although stiffness of the extracellular matrix in the infarct myocardium is associated with cardiac healing, the molecular mechanism of cardiac healing is not fully understood. We show that periostin, which is a matricellular protein, is important for the cardiac healing process after AMI. The expression of periostin protein was abundant in the infarct border of human and mouse hearts with AMI. We generated periostin(-/-) mice and found no morphologically abnormal cardiomyocyte phenotypes; however, after AMI, cardiac healing was impaired in these mice, resulting in cardiac rupture as a consequence of reduced myocardial stiffness caused by a reduced number of alpha smooth muscle actin-positive cells, impaired collagen fibril formation, and decreased phosphorylation of FAK. These phenotypes were rescued by gene transfer of a spliced form of periostin. Moreover, the inhibition of FAK or alphav-integrin, which blocked the periostin-promoted cell migration, revealed that alphav-integrin, FAK, and Akt are involved in periostin signaling. Our novel findings show the effects of periostin on recruitment of activated fibroblasts through FAK-integrin signaling and on their collagen fibril formation specific to healing after AMI.
Shimazaki et al. (Mon,) conducted a other in Acute myocardial infarction. Periostin gene knockout and gene transfer was evaluated on Cardiac healing and cardiac rupture. Periostin deficiency in mice impaired cardiac healing after acute myocardial infarction, resulting in cardiac rupture due to reduced myocardial stiffness and impaired collagen fibril formation.