Abstract 3639: The Potent Angiogenic Factor Periostin Accelerates Degeneration and Sclerosis of the Cardiac Valve Complex
We previously reported that chondromodulin-I (chm-I) is expressed in cardiac valves and maintains valvular function by preventing angiogenesis. Periostin has spliced isoform; it promotes embryonic valvulogenesis and left ventricular remodeling. However, its role in valvular heart disease (VHD) remains unknown. [Methods] (1) RT-PCR, quantitative PCR, Western blot, and immunostaining with periostin were performed in mouse and rat cardiac valves. (2) Human normal (n=8, 52.1 years in average) or degenerated (n=22, 63.0 years) cardiac valves were obtained from autopsied or surgical specimens with bicuspid, atheroscle-rotic, and rheumatic VHD. Immunostaining with periostin, chm-I, vWF, and VEGF and von Kossa stains was performed. (3) Tube formation assay and migration assay with a modified Boyden chamber using human endothelial cells were performed to investigate whether it had angiogenic or angioinhibitory activity. (4) Phenotype of wild type (WT) or periostin gene targeting (KO) mice fed with 4 months normal or high fat (HF) diet (n=6 each) was analyzed by 30 MHz echocardiography. [Results] (1) Periostin was specifically expressed at all cardiac valves and annuli from 10.5 dpc embryo to adult in the rodent heart. (2) RT-PCR revealed the shift from long to short periostin isoform after birth in mouse heart. (3) Periostin was observed at the subendothelial superficial layer, while chm-I was seen at the core layer of human normal cardiac valves, their expressions being mutually exclusive. (4) Interestingly, the periostin-positive area was markedly increased by 4-fold in the thickened degenerative valves, where the increased capillary density, VEGF expression, and calcium deposition was also observed. (5) Stimulation with recombinant periostin augmented the tube formation and increased the migrated cell number by 81% and 73%, respectively. (6) Echocardiography revealed that aortic valve thickness was increased, and the hyperechoic area in valve annuli suggesting calcification was significantly increased in WT+HF; it was reduced in KO+HF. The hyperechoic area in AV annulus: 0.38 / 0.88 / 0.61 mm2 in WT / WT+HF / KO+HF. [Conclusions] Periostin is a potent angiogenic factor and markedly accelerates degeneration and sclerosis of the cardiac valve complex.