Regulation of valvular interstitial cell calcification by adhesive peptide sequences.
Knowledge of how valvular interstitial cells (VICs) interact with the extracellular matrix (ECM) would aid in not only better understanding the etiology of valvular disease but also constructing appropriate environments for valve tissue engineering. In this work, the calcification of VICs cultured on ECM coatings (fibronectin, fibrin, collagen, and laminin) or ECM-derived peptide sequences (RGDS, YIGSR, and DGEA) was quantified via several techniques. Neutralizing antibodies to specific adhesion receptors were also applied, followed by quantification of phenotypic markers related to valve calcification. The calcification of VICs varied with the ECM component or peptide that was presented on the culture substrate. VICs calcified the most on RGDS and least on YIGSR and DGEA, while blocking specific receptors revealed that disruption of VIC binding via the alpha(5)beta(1) integrin or the 67-kDa laminin receptor had a dramatic calcification-stimulating effect. Binding via the alpha(2)beta(1) integrin did not alter calcification or VIC phenotype. These findings were translated to 3D peptide-modified scaffold environments that demonstrated varying levels of disease expression by VICs. Thus, specific adhesion receptors play a significant role in mediating the interactions between VICs and ECM that lead to calcification, which provides important information regarding the mechanisms of valvular disease and scaffold design for valve tissue engineering.
Gu
Xiaoxiao
X
Materials Science Program, University of Wisconsin, Madison, Wisconsin 53706, USA.
Masters
Kristyn S
KS
D000818:Animals; D001021:Aortic Valve / Q000737:chemistry / Q000473:pathology*; D001672:Biocompatible Materials / Q000737:chemistry*; D002118:Calcium / Q000737:chemistry; D005109:Extracellular Matrix / Q000378:metabolism*; D006018:Glycols / Q000737:chemistry; D020100:Hydrogels / Q000737:chemistry; D039081:Integrin alpha5beta1 / Q000378:metabolism; D016023:Integrins / Q000378:metabolism*; D008024:Ligands; D010455:Peptides / Q000737:chemistry*; D010641:Phenotype; D017474:Receptors, Laminin / Q000737:chemistry; D013552:Swine; D023822:Tissue Engineering / Q000379:methods*
D001672:Biocompatible Materials; D006018:Glycols; D020100:Hydrogels; D039081:Integrin alpha5beta1; D016023:Integrins; D008024:Ligands; D010455:Peptides; D017474:Receptors, Laminin; D002118:Calcium