Periostin is required for maturation and extracellular matrix stabilization of noncardiomyocyte lineages of the heart.

Abstract

The secreted periostin protein, which marks mesenchymal cells in endocardial cushions following epithelial-mesenchymal transformation and in mature valves following remodeling, is a putative valvulogenesis target molecule. Indeed, periostin is expressed throughout cardiovascular morphogenesis and in all 4 adult mice valves (annulus and leaflets). Additionally, periostin is expressed throughout the fibrous cardiac skeleton and endocardial cushions in the developing heart but is absent from both normal and/or pathological mouse cardiomyocytes. Periostin (peri(lacZ)) knockout mice exhibit viable valve disease, with neonatal lethality in a minority and latent disease with leaflet abnormalities in the viable majority. Surviving peri(lacZ)-null leaflets are truncated, contain ectopic cardiomyocytes and smooth muscle, misexpress the cartilage proteoglycan aggrecan, demonstrate disorganized matrix stratification, and exhibit reduced transforming growth factor-beta signaling. Neonatal peri(lacZ) nulls that die (14%) display additional defects, including leaflet discontinuities, delamination defects, and deposition of acellular extracellular matrix. Assessment of collagen production, 3D lattice formation ability, and transforming growth factor-beta responsiveness indicate periostin-deficient fibroblasts are unable to support normal valvular remodeling and establishment of a mature cardiac skeleton. Furthermore, pediatric stenotic bicuspid aortic valves that have lost normal extracellular matrix trilaminar stratification have greatly reduced periostin. This suggests that loss of periostin results in inappropriate differentiation of mesenchymal cushion cells and valvular abnormalities via a transforming growth factor-beta-dependent pathway during establishment of the mature heart. Thus, peri(lacZ) knockouts provide a new model of viable latent valve disease.

• Authors: Paige Snider, Robert B Hinton, Ricardo A Moreno-Rodriguez, Jian Wang, Rhonda Rogers, Andrew Lindsley, Fang Li, David A Ingram, Donald Menick, Loren Field, Anthony B Firulli, Jeffery D Molkentin, Roger Markwald, Simon J Conway
• Journal: Circulation research (Circ Res) Vol. 102 Issue 7 Pg. 752-60 (Apr 11 2008) ISSN: 1524-4571 [Electronic] United States
• PMID: 18296617 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Cell Adhesion Molecules
• Postn protein, mouse
• Transforming Growth Factor beta

Topics

• Animals
• Cell Adhesion Molecules (metabolism)
• Cell Differentiation (physiology)
• Cell Proliferation
• Cytoskeleton (metabolism, pathology)
• Disease Models, Animal
• Endocardium (metabolism, pathology)
• Extracellular Matrix (metabolism)
• Fibroblasts (metabolism, pathology)
• Heart Valve Diseases (metabolism, pathology)
• Mesoderm (metabolism, pathology)
• Mice
• Mice, Knockout
• Myocardium (metabolism, pathology)
• Myocytes, Cardiac (metabolism, pathology)
• Transforming Growth Factor beta (metabolism)