Abstract 3538: Periostin Accelerates Degeneration of the Cardiac Valve Complex by Promoting Angiogenesis and Matrix Metalloproteinase Production
Although we previously reported that an angioinhibitory factor chondromodulin I maintains cardiac valvular function by preventing angiogenesis (Nat Med, 2006), the mechanism underlying the progression of degenerative valvular heart disease (VHD) is poorly understood, and no preventive therapy has been established. Periostin is reported to be a stress-responsive, secreted protein that promotes embryonic cardiac valve development, but its physiological and pathophysiological roles in VHD remain unknown. We investigated the possible involvement of periostin in VHD, and if it is involved, how it affects the progression of VHD.
Methods and Results:
Periostin was specifically expressed in the cardiac valves and annuli from the E10.5 embryo to adulthood rodents.
In human normal cardiac valves (n=12), periostin was localized to the subendothelial superficial layer of the valve, and its expression pattern was mutually exclusive to that of chondromodulin I, but overlapped those of α-smooth muscle actin and vimentin.
Interestingly, periostin expression was increased 4-fold in the areas of angiogenesis in patients with atherosclerotic and rheumatic VHD (n=17).
A high-fat (HF) diet was administered to wild type (WT) and Periostin knockout (KO) mice for 4 months, and the cardiac valve complex was examined by 45-MHz echocardiography, immunohistochemis-try, and Western blot analysis (n=8 each). In WT mice, the HF diet markedly increased aortic valve thickening, angiogenesis and fibrosis of the annuli, and the expression of matrix metalloproteinase (MMP)-2 and MMP-13, in parallel with a 2.5-fold increase in the expression of periostin. However, these changes were strongly attenuated in KO mice.
In vitro studies using human endothelial cells revealed that periostin significantly promoted tube formation and mobilization, and inhibited apoptosis, thereby indicating its angiogenic activity.
Periostin increased the secretion of MMP-2 and MMP-13 from cultured valvular interstitial cells by 4-and 8-fold, respectively, without affecting their proliferation or apoptosis.
Conclusions: Periostin is specifically expressed in the cardiac valve complex, and accelerates its degeneration by promoting angiogenesis and MMP production.