These findings indicate that a dysregulation of DNA methylation in the promoter of H19 during calcific aortic valve disease is associated with a higher expression of this lncRNA, which promotes an osteogenic program by interfering with the expression of NOTCH1.
Finally, Notch1 and NOS3 (endothelial NO synthase) display an in vivo genetic interaction critical for proper valve morphogenesis and the development of aortic valve disease.
This finding was supported by the discovery of a NOTCH1 frameshift mutation in an unrelated family with similar aortic valve disease, suggesting that NOTCH1 haploinsufficiency was a genetic cause of aortic valve malformations and calcification.
These results suggest that NOTCH1 mutations cause an early developmental defect in the aortic valve and a later de-repression of calcium deposition that causes progressive aortic valve disease.
These results suggest that NOTCH1 mutations cause an early developmental defect in the aortic valve and a later de-repression of calcium deposition that causes progressive aortic valve disease.
Finally, Notch1 and NOS3 (endothelial NO synthase) display an in vivo genetic interaction critical for proper valve morphogenesis and the development of aortic valve disease.
Lipoprotein (a) [Lp(a)] has recently emerged as a causal, independent and genetic risk factor for cardiovascular disease and calcific aortic valve disease.
Evidence continues to mount for an important role for elevated plasma concentrations of lipoprotein(a) [Lp(a)] in mediating risk of atherothrombotic and calcific aortic valve diseases.
Lipoprotein(a) [Lp(a)] is an enigmatic lipoprotein which has been identified as a causal risk factor for coronary heart disease and calcific aortic valve disease.
Evaluation of Lipoprotein(a) Electrophoretic and Immunoassay Methods in Discriminating Risk of Calcific Aortic Valve Disease and Incident Coronary Heart Disease: The Multi-Ethnic Study of Atherosclerosis.
It is concluded that senescence-related fibrotic aortic valve disease in SAMP1 mice is associated with a decrease in serum klotho leading to inflammation, including macrophage infiltration and transforming growth factorβ-1/scleraxis-driven myofibroblast differentiation in aortic valves.