Periostin Reexpression in Heart Disease Contributes to Cardiac Interstitial Remodeling by Supporting the Cardiac Myofibroblast Phenotype

Cardiac muscle (the myocardium) is a unique arrangement of atria and ventricles that are spatially and electrically separated by a fibrous border. The spirally-arranged myocytes in both left and right ventricles are tethered by the component molecules of the cardiac extracellular matrix (ECM), including fibrillar collagen types I and III. Loss of normal arrangement of the ECM with either too little (as is observed in acute myocardial infarction) or too much (cardiac fibrosis in chronic post-myocardial infarction) is the primary contributor to cardiac dysfunction and heart failure. Matricellular proteins exist as non-structural signaling moieties in the ECM, and in the context of cardiac hypertrophy and heart failure, secreted 90 kDa periostin protein has attracted intense scrutiny during the past decade. Secreted periostin is now recognized for its important role in ECM development and maturation, as well as cellular adhesion. The novel mechanisms of periostin function include its role as a mediator of cell-to-matrix signaling, cell survival, and epithelial-mesenchymal transition (EMT). A number of recent studies have examined the hypothesis that periostin is a major contributor to ECM remodeling in the heart, and a number of very recent studies underscore its important role. This review examines recent developments in the mechanisms of periostin function in the normal heart and vasculature, and discusses recent advances which underpin its putative role in the development of cardiovascular disease. Periostin expression is very low at baseline in healthy tissues, but is re-expressed in damaged heart and in vessel walls after injury, in activated cardiac myofibroblasts and vascular smooth muscle cells, respectively. For this reason, periostin may be exploited for investigation of mechanisms of cardiac fibrosis, and we speculate that data generated from studies utilizing this approach may shed light on the timing for application of periostin-specific therapies to quell cardiac fibrosis and associated cardiac dysfunction.