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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:2165.)
© 2008 American Heart Association, Inc.

Integrative Physiology/Experimental Medicine

Clones of Interstitial Cells From Bovine Aortic Valve Exhibit Different Calcifying Potential When Exposed to Endotoxin and Phosphate

Marcello Rattazzi; Laura Iop; Elisabetta Faggin; Elisa Bertacco; Giacomo Zoppellaro; Ilenia Baesso; Massimo Puato; Gianluca Torregrossa; Gian Paolo Fadini; Carlo Agostini; Gino Gerosa; Saverio Sartore; Paolo Pauletto

From the Dipartimento di Medicina Clinica e Sperimentale (M.R., E.F., E.B., G.Z., I.B., M.P., G.P.F., C.A., P.P.), Dipartimento di Scienze Cardiologiche Toraciche e Vascolari (L.I., G.T., G.G.), Dipartimento di Scienze Biomediche Sperimentali (S.S.), Università degli Studi di Padova, Treviso, Italy.

Correspondence to Marcello Rattazzi, MD, Università degli Studi di Padova, Dipartimento di Medicina Clinica e Sperimentale, Medicina Interna I^, Ospedale Ca’ Foncello, Via Ospedale, 31100 Treviso, Italy. E-mail marcello.rattazzi{at}unipd.it

Objective— Our purpose was to study in vitro whether phenotypically-distinct interstitial cell clones from bovine aortic valve (BVIC) possess different calcifying potential in response to endotoxin (lipopolysaccharide [LPS]) and phosphate (Pi).

Methods and Results— Among various clones of BVIC obtained by limited dilution technique we selected 4 clones displaying different growth patterns and immunophenotypes. Uncloned and cloned cells were treated with combinations of LPS (100 ng/mL) and Pi (2.4 mmol/L). Uncloned BVIC showed increased alkaline phosphatase activity (ALP) after treatment with LPS, which resulted in calcification after addition of Pi. Among BVIC clones, only Clone 1 (fibroblast-like phenotype) showed a relevant increase in ALP after LPS treatment in parallel with prevention of smooth muscle (SM) -actin accumulation. No effect was observed in clonal cells harboring a more stable SM cell-like profile (Clone 4). None of the isolated clones calcified but mineralization was induced in the presence of LPS plus Pi when Clone 1 was cocultured with Clone 4 or after seeding on type I collagen sponges.

Conclusion— Endotoxin and phosphate can act as valve calcification promoters by targeting specific fibroblast-like interstitial valve cells that possess a unique procalcific potential.

In response to endotoxin and elevated phosphate levels a specific subtype of interstitial valve cells, harboring a fibroblast-like phenotype, acquires a unique procalcific profile, promoting collagen-matrix calcification.

Key Words: aortic valve • calcification • clones • endotoxin • phosphate