ABSTRACT
This research aimed to explore the molecular mechanism of microRNA (miR)-106b in cell apoptosis of atherosclerosis (AS). Human aortic endothelial cells (HAECs) were divided into control group, oxidized-low-density lipoproteins (ox-LDL) group, miR-106b NC+ox-LDL group, miR-106b mimics+ox-LDL group, miR-106b mimics+PTEN+ox-LDL group, and miR-106b mimics+empty+ox-LDL group. Real-time fluorescence quantitative polymerase chain reaction, cholecystokinin, TdT-mediated biotinylated nick end-labeling assay, luciferase reporter gene assay, and flow cytometry analysis were performed to determine the morphology, proliferation, and apoptosis in HSECs. Moreover, the levels of phosphatase and tensin homolog deleted on chromosome 10 (PTEN), Bcl-2, p-P13K, and p-AKT in HAECs were detected by western blot. MiR-106b was down-regulated in ox-LDL-induced HAECs. PTEN was the target gene of miR-106b-5p. Overexpression of PTEN inhibited the anti-apoptotic effect of miR-106b. Compared with the control group, the proportion and number of HAECs apoptosis and Bax, caspase-3, and caspase-9 expression in ox-LDL and miR-106b mimics+PTEN+ox-LDL groups were significantly increased (all P<0.05). Moreover, the activity of HAECs and Bcl-2 were decreased significantly (all P<0.05). Overexpression of miR-106b in ox-LDL-induced AS inhibited endothelial cell apoptosis. Furthermore, miR-106b might activate the PI3K/AKT pathway by down-regulating the expression of PTEN in ox-LDL-induced HAECs.
Subject(s)
Humans , Apoptosis , MicroRNAs/genetics , Endothelial Cells/metabolism , Atherosclerosis/metabolism , Lipoproteins, LDL/genetics , Signal Transduction , Up-Regulation , Cell Proliferation , Real-Time Polymerase Chain Reaction , Fluorescence , Lipoproteins, LDL/metabolismABSTRACT
Objective: To study associations of cerebrovascular metabolism genotypes and haplotypes with age at Alzheimer’s disease dementia (AD) onset and with neuropsychiatric symptoms according to each dementia stage. Methods: Consecutive outpatients with late-onset AD were assessed for age at dementia onset and Neuropsychiatric Inventory scores according to Clinical Dementia Rating scores, apolipoprotein E gene (APOE) haplotypes, angiotensin-converting enzyme gene (ACE) variants rs1800764 and rs4291, low-density lipoprotein cholesterol receptor gene (LDLR) variants rs11669576 and rs5930, cholesteryl ester transfer protein gene (CETP) variants I422V and TaqIB, and liver X receptor beta gene (NR1H2) polymorphism rs2695121. Results: Considering 201 patients, only APOE-ɛ4 carriers had earlier dementia onset in multiple correlations, as well as less apathy, more delusions, and more aberrant motor behavior. Both ACE polymorphisms were associated with less intense frontally mediated behaviors. Regarding LDLR variants, carriers of the A allele of rs11669576 had less anxiety and more aberrant motor behavior, whereas carriers of the A allele of rs5930 had less delusions, less anxiety, more apathy, and more irritability. CETP variants that included G alleles of I422V and TaqIB were mostly associated with less intense frontally mediated behaviors, while severely impaired carriers of the T allele of rs2695121 had more anxiety and more aberrant motor behavior. Conclusion: Though only APOE haplotypes affected AD onset, cerebrovascular metabolism genotypes were associated with differences in several neuropsychiatric manifestations of AD.
Subject(s)
Humans , Male , Female , Middle Aged , Aged , Aged, 80 and over , Cerebrovascular Disorders/genetics , Cerebrovascular Disorders/metabolism , Alzheimer Disease/genetics , Alzheimer Disease/metabolism , Genotype , Apolipoproteins E/genetics , Linear Models , Cerebrovascular Disorders/physiopathology , Cross-Sectional Studies , Age of Onset , Gene Dosage , Alleles , Cholesterol Ester Transfer Proteins/genetics , Genetic Association Studies , Alzheimer Disease/physiopathology , Late Onset Disorders , Liver X Receptors/genetics , Lipoproteins, LDL/genetics , Neuropsychological TestsABSTRACT
Familial hypercholesterolemia is an autosomal dominant inherited disorder, characterized by increased level of low-density lipoprotein cholesterol and lipid accumulation in tendons and arteries. It can cause premature atherosclerosis and increased risk of coronary heart disease [CHD]. Familial hypercholesterolemia is caused mainly by mutations in low-density lipoprotein receptor [LDLR] gene. The aim of this study was to analyze the LDLR gene mutations in a group of patients from Chaharmahal va Bakhtiari province. In this descriptive-lab based study, 57 suspected FH patients were screened for mutations in promoter and exons 1,3,5,11,13,15,16,17 and 18 of LDLR gene using PCR-SSCP strategy. Two different LDLR gene variations, including heterozygote mutation 283T>A and polymorphism 1959T>C, were identified in 1 and 9 FH Families studied, respectively. We conclude that LDLR gene mutation may not be the major cause of FH in the population studied and the cause of FH in Chaharmahal va Bakhtiari province remains to be detected in other loci or genes