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

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

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) α-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.

Original languageEnglish
Pages (from-to)2165-2172
Number of pages8
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume28
Issue number12
DOIs
StatePublished - Dec 2008
Externally publishedYes

Keywords

  • Aortic valve
  • Calcification
  • Clones
  • Endotoxin
  • Phosphate

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