Changes in extracellular calcium and phosphorus concentration affect vascular homeostasis

SANDOVAL M.; RAUSCHEMBERGER M.B.; DORRONSORO A.; CUTINI P.; SANTILLÁN G.; MASSHEIMER V.

Ciudad Autónoma de Buenos Aires

Congreso; XXX Reunión Anual de la Asociación Argentina de Osteología y Metabolismo Mineral (AAOMM); 2013

Changes in Ca or P serum promote vascular calcification (CaV) through independent mechanisms and/or by common pathways. We studied the effect of Ca and P on critical cellular processes of vascular homeostasis. The metabolic and phenotypic changes of endothelial cells (EC) and smooth muscle cells (VSMC) in an unfavorable environment represented by high P or Ca/P concentrations (10 mM glycerophosphate (GP) 4 mM Ca plus GP 5 mM) were assed. Osteoblastic VSMC transdifferentiation was evaluated using cell monolayers exposed GP 10 mM for 25 days. Alkaline phosphatase (ALP) activity was measured as osteoblastic marker differentiation. FAL activity levels and calcium content were significantly higher compared to native VSMC (FAL: 280 ± 31 vs 34 ± 1.8 IU/mg and Ca: 45 ± 6.6 vs 28 ± 1.9 mg/mg prot). A synergistic calcifying effect was detected using high Ca and P containing medium (FAL: 438 ± 35 IU mg, Ca: 71 ± 8.8 mg/mg prot). Calcium deposits were confirmed by alizarine red staining. Since endothelium nitric oxide (NO) production inhibits CaV, we studied the impact of a calcifying environment on NO production. High Ca concentrations (3; 5 mM) reduced NO bioavailability (48%; 44% reduction). Significant impairment in NO production was detected at all calcium concentrations tested (2, 3, 4 and 5 mM Ca). High calcium also affects the tissue´s ability to respond to its natural agonist acetylcholine (ACh). The stimulatory action of ACh on NO production at physiological conditions (1 mM) was suppressed when extracellular calcium increases (58% vs 2.4%). These results suggest that a procalcifying environment triggers detrimental events on the vascular system, prompting cardiovascular pathogenesis.