UNASSIGNED: @entity729 is an unfavorable event in the natural history of @entity731 that predicts @entity65 and mortality. However, increasing evidence suggests that different @entity730 patterns are associated with different or even opposite histopathological and clinical features, reflecting the dual relationship between @entity32 and @entity730 . In fact, initial @entity460 deposition in response to pro-inflammatory stimuli results in the formation of spotty or granular @entity730 ("microcalcification"), which induces further @entity32 . This vicious cycle favors @entity397 , unless an adaptive response prevails, with blunting of @entity32 and survival of vascular smooth muscle cells (VSMCs). VSMCs promote @entity82 and also undergo osteogenic transdifferentiation, with formation of homogeneous or sheet-like @entity730 ("macrocalcification"), that stabilizes the plaque by serving as a barrier towards @entity32 . Unfortunately, little is known about the molecular mechanisms regulating this adaptive response. The advanced glycation/lipoxidation endproducts (AGEs/ALEs) have been shown to promote @entity729 and @entity731 . Recent evidence suggests that two AGE/ALE receptors, @entity5764 and galectin-3, modulate in divergent ways, not only @entity32 , but also vascular osteogenesis, by favoring "microcalcification" and "macrocalcification", respectively. Galectin-3 seems essential for VSMC transdifferentiation into osteoblast-like cells via direct modulation of the WNT-b-catenin signaling, thus driving formation of "macrocalcification", whereas @entity5764 favors deposition of "microcalcification" by promoting and perpetuating @entity32 and by counteracting the osteoblastogenic effect of galectin-3. Further studies are required to understand the molecular mechanisms regulating transition from "microcalcification" to "macrocalcification", thus allowing to design therapeutic strategies which favor this adaptive process, in order to limit the adverse effects of established @entity731 .

The dark and bright side of XXXX .

@entity32 :: ('MESH:D007249', 'Disease') :: ['inflammation'] @entity82 :: ('MESH:D005355', 'Disease') :: ['fibrosis'] @entity5764 :: ('101669765', 'Gene') :: ['RAGE'] @entity730 :: ('MESH:D002114', 'Disease') :: ['calcification'] @entity397 :: ('MESH:D012421', 'Disease') :: ['plaque rupture'] @entity460 :: ('MESH:D002118', 'Chemical') :: ['calcium'] @entity729 :: ('MESH:D061205', 'Disease') :: ['vascular calcification', 'Vascular calcification'] @entity731 :: ('MESH:D050197', 'Disease') :: ['atherosclerotic calcification', 'atherosclerosis'] @entity65 :: ('MESH:D002318', 'Disease') :: ['cardiovascular morbidity']
@entity731 :: (MESH:D050197,Disease) :: ['atherosclerotic calcification']
