Cytosolic phospholipase A2alpha (cPLA2alpha) is an ubiquitously and constitutively expressed Ca2+-dependent enzyme which catalyzes the cleavage of arachidonic acid at the sn-2 position of phospholipids, with production of a downstream pro-inflammatory signaling molecules and subsequent increasing of its expression. Although growing evidence indicates that cPLA2alpha facilitates the release of pro-calcific matrix vesicles by hypertrophic chondrocytes during bone formation, its involvement in the pathological processes underlying the ectopic biomineralization of cardiovascular tissues is still poorly understood. Here, cPLA2alpha expression was assessed in different vascular mineralization contexts including experimental conditions of calcific induction and actual pathological conditions affecting aortic valves and aorta wall. cPLA2alpha resulted to be expressed by cells showing a fibroblastic phenotype, smooth muscle cells, macrophages, and endothelium for both different experimental and pathological conditions. Enzyme over-expression correlated with inflammatory response in in-vivo conditions and was actually elicited by inflammatory stimulations in in-vitro conditions, being directly involved also other pro-calcific agents such as phosphate at increasing concentrations. Notably, cPLA2alpha expression rate showed a direct correlation with that of cell and tissue mineralization, as revealed by Alizarin red staining, which was primed by a pro-calcific lipid-release-associated cell degeneration, as revealed by Cuprolinic blue and von Kossa reactions for electron microscopy. These shared immunohistochemical and ultrastructural patterns for all experimental and pathological calcific conditions suggest that cPLA2alpha might be actually involved in the etiopathogenesis of cardiovascular calcific diseases, so representing a potential target for novel therapeutic strategies aimed to counteract the progression of cardiovascular tissue mineralization.
Pro-calcific involvement of cytosolic phospholipase A2 alpha in different cardiovascular mineralization contexts
BONETTI, Antonella;ORTOLANI, Fulvia
2013-01-01
Abstract
Cytosolic phospholipase A2alpha (cPLA2alpha) is an ubiquitously and constitutively expressed Ca2+-dependent enzyme which catalyzes the cleavage of arachidonic acid at the sn-2 position of phospholipids, with production of a downstream pro-inflammatory signaling molecules and subsequent increasing of its expression. Although growing evidence indicates that cPLA2alpha facilitates the release of pro-calcific matrix vesicles by hypertrophic chondrocytes during bone formation, its involvement in the pathological processes underlying the ectopic biomineralization of cardiovascular tissues is still poorly understood. Here, cPLA2alpha expression was assessed in different vascular mineralization contexts including experimental conditions of calcific induction and actual pathological conditions affecting aortic valves and aorta wall. cPLA2alpha resulted to be expressed by cells showing a fibroblastic phenotype, smooth muscle cells, macrophages, and endothelium for both different experimental and pathological conditions. Enzyme over-expression correlated with inflammatory response in in-vivo conditions and was actually elicited by inflammatory stimulations in in-vitro conditions, being directly involved also other pro-calcific agents such as phosphate at increasing concentrations. Notably, cPLA2alpha expression rate showed a direct correlation with that of cell and tissue mineralization, as revealed by Alizarin red staining, which was primed by a pro-calcific lipid-release-associated cell degeneration, as revealed by Cuprolinic blue and von Kossa reactions for electron microscopy. These shared immunohistochemical and ultrastructural patterns for all experimental and pathological calcific conditions suggest that cPLA2alpha might be actually involved in the etiopathogenesis of cardiovascular calcific diseases, so representing a potential target for novel therapeutic strategies aimed to counteract the progression of cardiovascular tissue mineralization.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
