Methylation status of LDLR, PCSK9 and LDLRAP1 is associated with cardiovascular events in familial hypercholesterolemia.

Aim: Methylation of LDLR, PCSK9 and LDLRAP1 CpG sites was assessed in patients with familial hypercholesterolemia (FH). Methods: DNA methylation of was analyzed by pyrosequencing in 131 FH patients and 23 normolipidemic (NL) subjects. Results: LDLR, PCSK9 and LDLRP1 methylation was similar between FH patients positive (MD) and negative (non-MD) for pathogenic variants in FH-related genes. LDLR and PCSK9 methylation was higher in MD and non-MD groups than NL subjects (p < 0.05). LDLR, PCSK9 and LDLRAP1 methylation profiles were associated with clinical manifestations and cardiovascular events in FH patients (p < 0.05). Conclusion: Differential methylation of LDLR, PCSK9 and LDLRAP1 is associated with hypercholesterolemia and cardiovascular events. This methylation profile maybe useful as a biomarker and contribute to the management of FH.

[Box: see text].

Influence of antidepressant drugs on DNA methylation of ion channels genes in blood cells of psychiatric patients.

Aim: This study investigated the influence of antidepressant drugs on methylation status of KCNE1, KCNH2 and SCN5A promoters and ECG parameters in adult psychiatric patients. Materials & methods: Electrocardiographic evaluation (24 h) and blood samples were obtained from 34 psychiatric patients before and after 30 days of antidepressant therapy. Methylation of promoter CpG sites of KCNE1, KCNH2 and SCN5A was analyzed by pyrosequencing. Results: Three CpG and four CpG sites of KCNE1 and SCN5A, respectively, had increased % methylation after treatment. Principal component analysis showed correlations of the methylation status with electrocardiographic variables, antidepressant doses and patient age. Conclusion: Short-term treatment with antidepressant drugs increase DNA methylation in KCNE1 and SCN5A promoters, which may induce ECG alterations in psychiatric patients.

Transport of cowpea bean derived peptides and their modulator effects on mRNA expression of cholesterol-related genes in Caco-2 and HepG2 cells

This work studied the cell transport of peptidase-generated peptides from cowpea bean proteins and their effects on mRNA expression of cholesterol-related genes in intestinal and liver cells. The <= 3 kDa hydrolysate was obtained and incubated with Caco-2 intestinal cells using Transwell center dot plates. HepG2 liver cells were incubated with synthetic analogues of peptides (MELNAVSVVHS and MELNAVSVVSH) identified by "de novo" peptide sequencing in the Caco-2 monolayer permeates. The mRNA expression of NPC1L1, ABCA1 and ABCG1 was measured in Caco-2 cells, in the presence or absence of <= 3 kDa hydrolysate and the expression of HMGCR, SREBP2, LXRa, AMPK1, was determined in the HepG2 cells in the presence or absence of synthetic peptides. Exposure of Caco-2 cells to cowpea <= 3 kDa hydrolysate (2.5 and 5 mg/mL) increased ABCG1 expression at 6 h and 12 h. SREBP2, HMGCR and LDLR mRNA levels were reduced in HepG2 cells after 24 h of treatment with MELNAVSVVHS peptide (50 mu M and 100 mu M). These results suggest that MELNAVSVVHS peptide is able to cross intestinal barrier and to modulate genes involved in cholesterol homeostasis.

Transport of cowpea bean derived peptides and their modulator effects on mRNA expression of cholesterol-related genes in Caco-2 and HepG2 cells

This work studied the cell transport of peptidase-generated peptides from cowpea bean proteins and their effects on mRNA expression of cholesterol-related genes in intestinal and liver cells. The <= 3 kDa hydrolysate was obtained and incubated with Caco-2 intestinal cells using Transwell center dot plates. HepG2 liver cells were incubated with synthetic analogues of peptides (MELNAVSVVHS and MELNAVSVVSH) identified by "de novo" peptide sequencing in the Caco-2 monolayer permeates. The mRNA expression of NPC1L1, ABCA1 and ABCG1 was measured in Caco-2 cells, in the presence or absence of <= 3 kDa hydrolysate and the expression of HMGCR, SREBP2, LXRa, AMPK1, was determined in the HepG2 cells in the presence or absence of synthetic peptides. Exposure of Caco-2 cells to cowpea <= 3 kDa hydrolysate (2.5 and 5 mg/mL) increased ABCG1 expression at 6 h and 12 h. SREBP2, HMGCR and LDLR mRNA levels were reduced in HepG2 cells after 24 h of treatment with MELNAVSVVHS peptide (50 mu M and 100 mu M). These results suggest that MELNAVSVVHS peptide is able to cross intestinal barrier and to modulate genes involved in cholesterol homeostasis.