Transforming Growth Factor-β1 Mechanisms in Aortic Valve Calcification: Increased Alkaline Phosphatase and Related Events

Clones of Interstitial Cells From Bovine Aortic Valve Exhibit Different Calcifying Potential When Exposed to Endotoxin and Phosphate

“…However, when Clone 1 was seeded on collagen scaffolds the treatment with Pi was sufficient to induce the calcification of the matrix, accompanied by apoptosis of clonal cells. Previous studies carried out in both VIC and SMC have demonstrated that blocking apoptosis pathways can abate the in vitro process of calcification, 16,20 suggesting that apoptosis could represent the final differentiation stage of cells acquiring a procalcific profile (as it happens at the end of chondrocyte maturation). Apoptosis cannot be considered per se a trigger for calcific degeneration of vascular tissues as suggested by Clarke et al, 21 who showed that the chronic induction of apoptosis in vascular SMC was not accompanied in vivo by calcium deposition in the arterial wall.…”

“…Canine, sheep, and human aortic VIC cultures yield in vitro nodules, as well. 11,16 However calcification of these VIC has not been studied using clonal cell populations. A clonal study was instead performed by Demer's group to identify the presence in the bovine arterial wall of calcifying valve cells (CVC), a specific subset of SMC that spontaneously calcifies in vitro, forms nodules and retains a mesenchymal multilineage potential (chondrogenic, leiomyogenic, stromogenic).…”

Identification and Characterization of Aortic Valve Mesenchymal Progenitor Cells with Robust Osteogenic Calcification Potential

“…In some cases, such as in response to transforming growth factor-␤, calcification in vitro is rapid and dystrophic, driven by apoptosis of VICs and involving alkaline phosphatase activity. 22,23 Apoptotic cells and transforming growth factor-␤ are also associated with dystrophic valve calcification in vivo. [22][23][24] Conversely, evidence of bone-related matrix proteins, 21,25,26 transcription factors, 26 and mineral 21 in VIC cultures suggests that calcification can occur in vitro via an osteogenic process, which is consistent with evidence in vivo.…”

“…22,23 Apoptotic cells and transforming growth factor-␤ are also associated with dystrophic valve calcification in vivo. [22][23][24] Conversely, evidence of bone-related matrix proteins, 21,25,26 transcription factors, 26 and mineral 21 in VIC cultures suggests that calcification can occur in vitro via an osteogenic process, which is consistent with evidence in vivo. 4,5,27,28 However, even in VIC cultures that express bone markers, calcified nodules are reported to contain a core of dead cells, 21 which is not observed in bone nodules formed by osteoprogenitors harvested from established sources.…”

Molecular-Genetic Factors, Associated With Aortic Stenosis Development

“…Данные об активности TGFβ1 пути в патогенезе АС подтверждены в экспериментальных моделях на животных [13], а также данными исследований с количественной ПЦР, показавшей повышенный уровень экспрессии мРНК генов TGFβ1, щелочной фосфатазы и ММР-9 в кальцинированном аорталь-ном клапане больных АС [18].…”