ELN and hyperinsulinemic hypoglycemia, familial, 4: A recent study by Dave et al. linked elastin deficiency to NOTCH signaling (59): although elastin deficiency does not directly contribute to atherosclerosis, degradation of elastin may allow lipid infiltration into atherosclerotic plaques; elastin deficiency in VSMC resulted in reduced levels of DNA methyltransferase 1 (DNMT1) and DNA methylation (an epigenetic marker that drives gene silencing), which induces the expression of key NOTCH pathway genes Jagged1, γ-secretase catalytic subunits PSEN1 and PSEN2 and triggers NOTCH3 activation.