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COLLAGEN CROSS-LINKING ENZYMES ARE INVOLVED IN VASCULAR SMOOTH MUSCLE CELLS CALCIFICATION
Autores:
EVA JOVER GARCÍA
,
ANA SILVENTE LLORENTE
,
FRANCISCO MARIN ORTUÑO
, CRISTINA RODRIGUEZ, JOSÉ MARTÍNEZ GONZÁLEZ, CARMEN MARÍA PUCHE,
MARIANO VALDES CHAVARRI
,
DIANA HERNÁNDEZ ROMERO
,
Grupos de investigación:
[GI/IMIB/C002/2011] CARDIOLOGIA CLINICA Y EXPERIMENTAL
Comunicación:
Antecedentes:
Vascular calcification shares several comonalities with osteogenic processes including osteoblast-like cell differentiation of vascular smooth muscle cells (VSMC) and extracel lular matrix (ECM) synthesis and mineralization. Intracellular and extracellular hydroxylase enzymes, such as PLOD1 and LOX1, render collagen enriched-ECM maduration and stabilization. We aimed to assess the involvement o f those enzymes in hyperphosphatemia-dependent calcificacion in vitro
Métodos:
Hyperphospathemia (HPM) was used to induce active differentiation of VSMC onto functional osteoblast-like cells as demonstrated by extracellular matrix mineralization and osteoblast-markers expression. The experiments were carriedout in primary cultured mouse and human VSMC. Two lines of mouse VSMC (mVSMC) were used: wild-type mVSMC and transgenic mVSMC over-expressing human recombinant LOX1. Well-known inhibitors for LOX and PLOD1 activity,including ?-aminopropionitrile (BAPN) and 2,2'-dypiridil, respectively, were used in combination with HPM media.
Resultados:
The over-expression of LOX was associated with a significant increase of ECM mineralization and osteogenic markers expression in mVSMC. Thereby, using BAPN on hVSMC leaded to a significant reduction of ECM mineralization, osteoblast-related gene expression, and lowered phenotype transdifferentiation as demostrated by SM22? and osteocalcin protein levels. BAPN was also associated with lower levels of soluble collagen compared to HPM. Using 2,2'dipyridil on mVSMC or hVSMC was associated with lowered ECM mineralization and regulates the synthesis of collagen and osteoblast commitment.
Conclusiones:
Our findings arise the importance of ECM regulation during vascular calcification. ECM mineralization in vascular calcification may exert regulatory effects on VSMC differentiation into osteoblast-lile cells as occurs during physiological osteogenesis.
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