Genetic Basis of Atherosclerosis: Part II

Lusis, Aldons J.; Fogelman, Alan M.; Fonarow, Gregg C.

doi:10.1161/01.cir.0000143098.98869.f8

Cited by 66 publications

(46 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Densitometric analysis of blots showed no difference in eNOS expression between the diet groups. (3b) Vascular measurements of NO production using Fe-(DETC) 2 Potassium chloride-(4a) and phenylephrine-induced (4b) vasoconstriction. Acetylcholinemediated, endothelium-dependent relaxation in the absence (4c), or presence (4d) of the superoxide scavenger Tiron.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Ezetimibe potently reduces vascular inflammation and arteriosclerosis in eNOS-deficient ApoE ko mice

Kuhlencordt¹,

Padmapriya²,

Rützel³

et al. 2009

Atherosclerosis

View full text Add to dashboard Cite

Objective-Hypercholesterolemia is associated with decreased vascular nitric oxide bioavailability and deletion of endothelial nitric oxide synthase (eNOS) markedly accelerates atherosclerosis development in apolipoprotein E knockout (apoE ko) mice. The current study tests whether atheroprotection provided by a lipid lowering therapy with Ezetimibe depends on eNOS.Methods/Results-ApoE ko and apoE/eNOS double ko (dko) mice received a high fat diet with or without 0.05% Ezetimibe. Ezetimibe significantly reduced plasma cholesterol concentrations and atherogenic lipoproteins in both genotypes to a similar extent. Moreover, the drug reduced vascular inflammation, as it significantly reduced Vascular Cell Adhesion Molecule-1 (VCAM-1) expression and vascular CD14 expression, a marker for mononuclear cell infiltration, in both genotypes. Neither NOS protein expression nor vascular reactivity of aortic rings were changed in apoE ko mice following Ezetimibe treatment. Significant lesion reduction was seen in Ezetimibe treated male and female apoE ko and apoE/eNOS dko animals (p≤0.05). Interestingly, the drug mediated additional atheroprotection in male apoE ko, compared to male eNOS dko mice, suggesting that lipid lowering does provide additional eNOS dependent atheroprotection in this experimental group.Conclusion-Lipid lowering with Ezetimibe potently reduces atherosclerosis and vascular inflammation independent of eNOS. Moreover, Ezetimibe did not exert any effects on eNOS protein expression or enzyme activity. However, additional atheroprotection by Ezetimibe was observed in eNOS competent apoE ko mice, suggesting that some of the drug's antiatherosclerotic effects are mediated by the eNOS pathway.

show abstract

Section: Discussionmentioning

confidence: 99%

“…Atherosclerosis, the primary cause of coronary artery disease (CAD) and stroke, is a complex inflammatory disease that involves multiple cell types, genes and environmental factors 1,2 . Elevated plasma cholesterol levels and low-density-lipoprotein cholesterol (LDL-C) in particular are independent predictors of CAD.…”

Section: Introductionmentioning

confidence: 99%

Ezetimibe potently reduces vascular inflammation and arteriosclerosis in eNOS-deficient ApoE ko mice

Kuhlencordt¹,

Padmapriya²,

Rützel³

et al. 2009

Atherosclerosis

View full text Add to dashboard Cite

show abstract

“…3 Numerous studies indicate that levels of triglycerides and cholesterol in the blood are influenced by variations in genes which control or influence lipid metabolism. 4,5 Among the many candidate genes are the apolipoprotein C-III (ApoC3), apolipoprotein A-V gene (ApoA5) and lipoprotein lipase (LPL) genes. (Table 1).…”

Section: Introductionmentioning

confidence: 99%

Allelic variation in ApoC3, ApoA5 and LPL genes and first and second generation antipsychotic effects on serum lipids in patients with schizophrenia

et al. 2007

View full text Add to dashboard Cite

Schizophrenic patients who are treated with antipsychotics, especially second generation antipsychotics, such as clozapine and olanzapine, manifest an increase in cholesterol and triglycerides as well as other changes associated with diabetes or the metabolic syndrome. Previous studies have shown that polymorphisms in several genes that regulate lipid metabolism can influence the levels of these lipids and response to drug treatment. We have investigated in an exploratory study whether polymorphisms in the apolipoprotein C-III (ApoC3), apolipoprotein A-V gene (ApoA5) and lipoprotein lipase genes influence differential lipid response to treatment with three second generation antipsychotics-olanzapine, clozapine and risperidone-or treatment with a first generation antipsychotic. A total of 189 patients with schizophrenia or schizoaffective disorder who were being treated with a single antipsychotic were studied in a cross-sectional study design in which fasting serum cholesterol and triglycerides and selected single-nucleotide polymorphosms (SNPs) in the three lipid metabolism genes were assessed. The treatment with antipsychotic monotherapy makes drug haplotype ascertainment less complex. Our analyses showed several nominally significant drug Â gene and drug Â haplotype interactions. The rarer C allele or the ApoA5_1131 (T/C) SNP was associated with higher cholesterol levels in patients treated with first generation antipsychotics and lower cholesterol levels in patients treated with olanzapine or clozapine. The rarer C allele of the ApoA5_SW19 (G/C) SNP was associated with higher cholesterol in risperidone-treated patients. An ApoA5 CG haplotype was associated with decreased cholesterol in olanzapine-or clozapine-treated patients and higher cholesterol in patients treated with first generation antipsychotics. The presence of the rarer T allele of the ApoC3_1100 (C/T) SNP or the presence of the ApoC3 TG haplotype was associated with decreased triglyceride levels in patients treated with olanzapine or clozapine and a nonsignificant trend for increased triglycerides in patients treated with first generation antipsychotics. The presence of the ApoC3 CC haplotype was associated with increased triglycerides in patients treated with olanzapine or clozapine. The overall magnitude of the effects was not large. These results provide a potential initial step toward a pharmacogenetic approach to selection of antipsychotic treatment which may help minimize the side effect of increases in serum lipids.

show abstract

“…Coincidently, it is correlated to the formation of MMP-9. MMP-9 in patients suffering from an acute coronary syndrome seems to be directly correlated to hs-CRP [28,29]. This is an indication towards a close connection between inflammatory status and plaque stability [30].…”

Section: Discussionmentioning

confidence: 99%

The significance of lipid peroxidation in cardiovascular disease

Siegel

Ermilov

Pries

et al. 2014

Colloids and Surfaces A: Physicochemical and Engineering Aspect

View full text Add to dashboard Cite

Background: The metabolic syndrome describes a cluster of cardiovascular risk factors that frequently appear together. Its diagnosis is generally based on several well-recognized indicators in clinical practice, such as abdominal obesity, elevated triglycerides, reduced highdensity lipoprotein, raised blood pressure, and elevated fasting plasma glucose. Today, decisive importance must be attached to the metabolic syndrome since it leads to increased morbidity and mortality, and thus to a decreased life expectancy, and to higher direct and indirect healthcare costs. This is also due to the fact that its symptomatology irradiates on many organs of the body, which may thereby be damaged. Methods: In the present clinical trial on 11 metabolic syndrome patients treated with Ginkgo biloba (EGb 761, 2  120 mg/d) for two months, ellipsometry, fluorescence microscopy, photometric methods, ELISAs and EIAs were applied for biosensor profiling of metabolic syndrome risk, status and treatment outcome. Results: A spectrum of more than 20 arteriosclerotic, cytokinic, inflammatory, lipidic, and oxidative stress biomarkers served for a detailed diagnosis and therapy monitoring. After medication, the ratio oxLDL/LDL was reduced by 21.0%, 8-iso-PGF 2α 39.8%, MPO 29.6%, IL-6 12.9%, hs-CRP 39.3%, Lp(a) 26.3%, MMP-9 32.9%, insulin 9.4%, HOMA-IR 14.0%, ALP 14.8%, CREA 11.3%, URAC 10.6%, in vitro modelled nanoplaque formation 14.3% and size 23.4%, whereas SOD was augmented by 17.7%, GPx 11.6%, cAMP 43.5%, and cGMP 32.9%. Special focus was concentrated on the significance of lipid peroxidation for cardio-cerebro-vascular diseases. Through multiple correlations between the biomarkers and clinical parameters, their significance for and involvement in several clinical pictures could be elucidated. Conclusion: The present clinical observational study was helpful in unravelling this network of biomarker interactions and demonstrated its usefulness for theranostics. For personalized medicine, the selection of the biomarkers is of decisive importance. On the background of a growing obesity among children and adolescents with an increase in prevalence of the metabolic syndrome, diagnosing this syndrome in young subjects may be helpful in identifying a population of risk for increased subclinical arteriosclerosis.

show abstract

Genetic Basis of Atherosclerosis: Part II

Cited by 66 publications

References 34 publications

Ezetimibe potently reduces vascular inflammation and arteriosclerosis in eNOS-deficient ApoE ko mice

Ezetimibe potently reduces vascular inflammation and arteriosclerosis in eNOS-deficient ApoE ko mice

Allelic variation in ApoC3, ApoA5 and LPL genes and first and second generation antipsychotic effects on serum lipids in patients with schizophrenia

The significance of lipid peroxidation in cardiovascular disease

Contact Info

Product

Resources

About