Neonatal and adult cardiovascular pathophysiological remodeling and repair: developmental role of periostin.

摘要: The neonatal heart undergoes normal hypertrophy or compensation to complete development and adapt increased systolic pressures. Hypertrophy wall stiffness are associated with a doubling of the number fibroblasts de novo formation collagen. Normal postnatal remodeling is completed within 3-4 weeks after birth but can be rekindled in adult life response environmental signals that lead pathological hypertrophy, fibrosis, failure. trigger fibroblast collagen (fibrosis) as well origin differentiation cardiac lineage not understood. Using mice studies single-cell engraftment model, we have shown derived from two extracardiac sources: embryonic proepicardial organ recruitment circulating bone marrow cells hematopoietic stem cell origin. Periostin, matricellular protein, normally expressed differentiating its expression elevated several fold Our hypothesis periostin profibrogenic (i.e., it promotes progenitor mesenchymal into their secretion compaction collagen) was tested using isolated cultured embryonic, neonatal, wild-type periostin-null, nonmyocyte populations. findings indicate abrogation by targeted gene deletion inhibits permits misdirection cardiomyocyte lineage. However, if forced express periostin, they became fibroblasts. Periostin plays significant role promoting fibrogenesis residual stress, tensile testings indicated played an essential regulatory maintaining biomechanical properties myocardium. These protein fibrogenesis, cardiomyocytes, for