scholarly journals The Epigenome in Atherosclerosis

2020 ◽  
Author(s):  
Sarah Costantino ◽  
Francesco Paneni
Keyword(s):  
Vascular Disease ◽  
Posttranslational Modifications ◽  
Epigenetic Modifications ◽  
Atherosclerotic Vascular Disease ◽  
Biological Regulation ◽  
Genetic Changes ◽  
Epigenetic Biomarkers ◽  
The Individual ◽  
Novel Therapeutic Strategies ◽  
Vascular Oxidative Stress

AbstractEmerging evidence suggests the growing importance of “nongenetic factors” in the pathogenesis of atherosclerotic vascular disease. Indeed, the inherited genome determines only part of the risk profile as genomic approaches do not take into account additional layers of biological regulation by “epi”-genetic changes. Epigenetic modifications are defined as plastic chemical changes of DNA/histone complexes which critically affect gene activity without altering the DNA sequence. These modifications include DNA methylation, histone posttranslational modifications, and non-coding RNAs and have the ability to modulate gene expression at both transcriptional and posttranscriptional level. Notably, epigenetic signals are mainly induced by environmental factors (i.e., pollution, smoking, noise) and, once acquired, may be transmitted to the offspring. The inheritance of adverse epigenetic changes may lead to premature deregulation of pathways involved in vascular damage and endothelial dysfunction. Here, we describe the emerging role of epigenetic modifications as fine-tuners of gene transcription in atherosclerosis. Specifically, the following aspects are described in detail: (1) discovery and impact of the epigenome in cardiovascular disease, (2) the epigenetic landscape in atherosclerosis; (3) inheritance of epigenetic signals and premature vascular disease; (4) epigenetic control of lipid metabolism, vascular oxidative stress, inflammation, autophagy, and apoptosis; (5) epigenetic biomarkers in patients with atherosclerosis; (6) novel therapeutic strategies to modulate epigenetic marks. Understanding the individual epigenetic profile may pave the way for new approaches to determine cardiovascular risk and to develop personalized therapies to treat atherosclerosis and its complications.

scholarly journals Postprenylation CAAX Processing Is Required for Proper Localization of Ras but Not Rho GTPases

2005 ◽  
Vol 16 (4) ◽  
pp. 1606-1616 ◽  
Author(s):  
David Michaelson ◽  
Wasif Ali ◽  
Vi K. Chiu ◽  
Martin Bergo ◽  
Joseph Silletti ◽  
...  
Keyword(s):  
Posttranslational Modifications ◽  
Protein Trafficking ◽  
Rho Gtpases ◽  
Ras Proteins ◽  
Rho Proteins ◽  
Carboxyl Methylation ◽  
C Terminus ◽  
Individual Contributions ◽  
The Individual ◽  
And Function

The CAAX motif at the C terminus of most monomeric GTPases is required for membrane targeting because it signals for a series of three posttranslational modifications that include isoprenylation, endoproteolytic release of the C-terminal– AAX amino acids, and carboxyl methylation of the newly exposed isoprenylcysteine. The individual contributions of these modifications to protein trafficking and function are unknown. To address this issue, we performed a series of experiments with mouse embryonic fibroblasts (MEFs) lacking Rce1 (responsible for removal of the –AAX sequence) or Icmt (responsible for carboxyl methylation of the isoprenylcysteine). In MEFs lacking Rce1 or Icmt, farnesylated Ras proteins were mislocalized. In contrast, the intracellular localizations of geranylgeranylated Rho GTPases were not perturbed. Consistent with the latter finding, RhoGDI binding and actin remodeling were normal in Rce1- and Icmt-deficient cells. Swapping geranylgeranylation for farnesylation on Ras proteins or vice versa on Rho proteins reversed the differential sensitivities to Rce1 and Icmt deficiency. These results suggest that postprenylation CAAX processing is required for proper localization of farnesylated Ras but not geranygeranylated Rho proteins.

Oxidized ApoC1 on MALDI-TOF and glycated-ApoA1 band on gradient gel as potential diagnostic tools for atherosclerotic vascular disease

2013 ◽  
Vol 420 ◽  
pp. 69-75 ◽  
Author(s):  
Chiz-Tzung Chang ◽  
Hsin-Yi Liao ◽  
Chia-Ming Chang ◽  
Chia-Ying Chen ◽  
Chu-Huang Chen ◽  
...  
Keyword(s):  
Vascular Disease ◽  
Diagnostic Tools ◽  
Atherosclerotic Vascular Disease ◽  
Maldi Tof

Abstract TP297: Predictors of Intracranial Hemorrhage in Patients with Atherosclerotic Vascular Disease: Observations from the TRA 2°P-TIMI 50 Trial

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Marc P Bonaca ◽  
Jay P Mohr ◽  
Mark J Alberts ◽  
Sebastian F Ameriso ◽  
Graeme J Hankey ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Vascular Disease ◽  
Renal Dysfunction ◽  
Intracranial Hemorrhage ◽  
Rare Event ◽  
Arterial Disease ◽  
Male Gender ◽  
Atherosclerotic Vascular Disease ◽  
Clinical Predictors ◽  
History Of

Intracranial hemorrhage (ICH) is a rare event that is difficult to predict and often has devastating consequences. Clinical predictors of ICH in stable patients with atherosclerosis are not well described. Methods: We evaluated the clinical correlates of ICH risk in patients randomized to placebo (N=13,166) in the TRA 2°P-TIMI 50 trial, a multinational trial of patients with atherothrombosis randomized to vorapaxar or placebo added to standard therapy. Eligible patients had a history of myocardial infarction, peripheral arterial disease, or recent ischemic stroke (2 wks to 12 mo.). ICH was adjudicated by an independent CEC. Results: A total of 53 ICH events (0.5% at 3 years) occurred during follow up in the placebo group. 94% of patients were receiving aspirin, 5% a thienopyridine alone, and 57% dual antiplatelet therapy. Overall, age, sex, prior ischemic stroke, and renal dysfunction were significantly associated with ICH (Table 1). After adjustment age, male gender, and prior ischemic stroke remained significantly associated with an increased hazard of ICH (Figure 1). Notably, the predictors differed between qualifying groups. After adjustment renal dysfunction (p=0.018) and diabetes (p=0.073) were associated with ICH in the MI/PAD group. In contrast, only male gender was associated with ICH in the CVD group (p=0.048). Conclusions: Advanced age, male gender, and history of ischemic stroke are associated with an increased hazard of ICH in patients with a history of atherothrombosis. Predictors of ICH vary depending on background vascular disease. In patients with MI/PAD and no recent stroke, traditional risk factors including diabetes and renal dysfunction are associated with ICH.

The Distinctive Nature of Atherosclerotic Vascular Disease in Diabetes: Pathophysiological and Morphological Insights

2012 ◽  
Vol 12 (3) ◽  
pp. 280-285 ◽  
Author(s):  
Rishi Puri ◽  
Yu Kataoka ◽  
Kiyoko Uno ◽  
Stephen J. Nicholls
Keyword(s):  
Vascular Disease ◽  
Atherosclerotic Vascular Disease

scholarly journals Adiponectin, leptin, and resistin in patients with aortic stenosis without concomitant atherosclerotic vascular disease

2011 ◽  
Vol 121 (10) ◽  
pp. 352-360 ◽  
Author(s):  
Renata Kolasa-Trela ◽  
Tomasz Miszalski-Jamka ◽  
Grzegorz Grudzień ◽  
Ewa Wypasek ◽  
Magdalena Kostkiewicz
Keyword(s):  
Aortic Stenosis ◽  
Vascular Disease ◽  
Atherosclerotic Vascular Disease

scholarly journals Minireview: Epigenetic Programming of Diabetes and Obesity: Animal Models

Endocrinology ◽  
2012 ◽  
Vol 153 (3) ◽  
pp. 1031-1038 ◽  
Author(s):  
Yoshinori Seki ◽  
Lyda Williams ◽  
Patricia M. Vuguin ◽  
Maureen J. Charron
Keyword(s):  
Metabolic Disease ◽  
Animal Models ◽  
Posttranslational Modifications ◽  
Cytosine Methylation ◽  
Metabolic Diseases ◽  
Later Life ◽  
Epigenetic Modifications ◽  
Micro Rna ◽  
Fetal Origins ◽  
Diabetes And Obesity

A growing body of evidence suggests that the intrauterine (IU) environment has a significant and lasting effect on the long-term health of the growing fetus and the development of metabolic disease in later life as put forth in the fetal origins of disease hypothesis. Metabolic diseases have been associated with alterations in the epigenome that occur without changes in the DNA sequence, such as cytosine methylation of DNA, histone posttranslational modifications, and micro-RNA. Animal models of epigenetic modifications secondary to an altered IU milieu are an invaluable tool to study the mechanisms that determine the development of metabolic diseases, such as diabetes and obesity. Rodent and nonlitter bearing animals are good models for the study of disease, because they have similar embryology, anatomy, and physiology to humans. Thus, it is feasible to monitor and modify the IU environment of animal models in order to gain insight into the molecular basis of human metabolic disease pathogenesis. In this review, the database of PubMed was searched for articles published between 1999 and 2011. Key words included epigenetic modifications, IU growth retardation, small for gestational age, animal models, metabolic disease, and obesity. The inclusion criteria used to select studies included animal models of epigenetic modifications during fetal and neonatal development associated with adult metabolic syndrome. Experimental manipulations included: changes in the nutritional status of the pregnant female (calorie-restricted, high-fat, or low-protein diets during pregnancy), as well as the father; interference with placenta function, or uterine blood flow, environmental toxin exposure during pregnancy, as well as dietary modifications during the neonatal (lactation) as well as pubertal period. This review article is focused solely on studies in animal models that demonstrate epigenetic changes that are correlated with manifestation of metabolic disease, including diabetes and/or obesity.

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