Background And Purpose: Atherosclerosis is a progressive inflammatory disease and can develop in large arteries such as carotid and femoral arteries or medium-sized muscular arteries of the heart. Previous predominantly experimental studies suggested an important role of chemokines in the development of atherosclerosis. The main aim of this study was to examine potential effect of the CCR5-del32 mutation on systemic inflammation, intima-media thickness in carotid and femoral arteries, and on the indices of cardiovascular disease.
Methods: In the present study, we have examined the association of a common functional 32-bp frameshift deletion mutation in a chemokine receptor (CCR5) in relation to inflammation and atherosclerosis. CCR5 is a G protein-coupled receptor involved in inflammatory response and regulation of leukocytes activation and migration. Genetic screening of this mutation was carried out on a well-known and previously described cohort of Bruneck (n=826) using polymerase chain reaction.
Results: Screening was successful in 810 subjects of whom 7 were homozygous, 102 were heterozygous, and 701 were normal. The mutation was associated with significantly lower levels of C-reactive protein in a dose-dependent manner. Moreover, CCR5-del32 was associated with a significantly lower carotid intima-media thickness in the common carotid artery (del32/del32, 837+/-8 microm; wt/del32, 909+/-21 microm; wt/wt, 958+/-8 microm; P=0.007 after multivariable adjustment). Furthermore, incident cardiovascular disease (1995 to 2005) was markedly reduced in del32 homozygotes and heterozygotes subjects compared with wild-type homozygotes (del32/del32=0%, wt/del32=7.8%, wt/wt=14.8%, P=0.020). Findings equally applied to coronary artery and cerebrovascular disease.
Conclusions: The chemokine receptor CCR5-del32 frameshift mutation is associated with low levels of C-reactive protein, decreased intima-media thickness, and cardiovascular disease risk. These findings are consistent with the hypothesis that the chemokine receptor CCR5 is involved in the mediation of low-grade systemic inflammation and may play a role in human atherosclerosis and cardiovascular disease.
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http://dx.doi.org/10.1161/STROKEAHA.107.504381 | DOI Listing |
Genet Epidemiol
January 2025
Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.
Large-scale gene-environment interaction (GxE) discovery efforts often involve analytical compromises for the sake of data harmonization and statistical power. Refinement of exposures, covariates, outcomes, and population subsets may be helpful to establish often-elusive replication and evaluate potential clinical utility. Here, we used additional datasets, an expanded set of statistical models, and interrogation of lipoprotein metabolism via nuclear magnetic resonance (NMR)-based lipoprotein subfractions to refine a previously discovered GxE modifying the relationship between physical activity (PA) and HDL-cholesterol (HDL-C).
View Article and Find Full Text PDFFree Radic Res
January 2025
Radiation Biology & Health Sciences Division, Bio-science Group, Bhabha Atomic Research Centre, Trombay, Mumbai-400085, India.
Free radicals have been implicated in the pathogenesis of cancer along with cardiovascular, neurodegenerative, pulmonary and inflammatory disorders. Further, the relationship between oxidative stress and disease is distinctively established. Clinical trials using anti-oxidants for the prevention of disease progression have indicated some beneficial effects.
View Article and Find Full Text PDFEur Heart J Cardiovasc Imaging
January 2025
Sorbonne Université, unité d'imagerie cardiovasculaire et thoracique, Hôpital La Pitié Salpêtrière (AP-HP), Laboratoire d'Imagerie Biomédicale, INSERM, CNRS, Institute of Cardiometabolism and Nutrition, ACTION Group, Paris, France.
Purpose: Epicardial adipose tissue (EAT) could contribute to the specific atherosclerosis profile observed in premature coronary artery disease (pCAD) characterized by accelerated plaque burden (calcified and non-calcified), high risk plaque features (HRP) and ischemic recurrence. Our aims were to describe EAT volume and density in pCAD compared to asymptomatic individuals matched on CV risk factors and to study their relationship with coronary plaque severity extension and vulnerability.
Materials And Methods: 208 patients who underwent coronary computed tomography angiography (CCTA) were analyzed.
Public Health Nutr
January 2025
Medical Research Council Research Unit for Hypertension and Cardiovascular Disease, North-West University, Potchefstroom, South Africa.
Objective: This study assessed the association between baseline sociodemographic variables, body composition and 4-year changes in the intake of food groups, including sugar sweetened beverages (SSBs) among children, after implementation of the health promotion levy.
Design: Prospective cohort study.
Setting: 10 schools in North West Province, South Africa.
EClinicalMedicine
October 2024
Toronto 3D Knowledge Synthesis and Clinical Trials Unit, Clinical Nutrition and Risk Factor Modification Center, St. Michael's Hospital, Unity Health Toronto, Toronto, ON M5B 1W8, Canada.
Background: Use of health applications (apps) to support healthy lifestyles has intensified. Different app features may support effectiveness, including gamification defined as the use of game elements in a non-game situation. Whether health apps with gamification can impact behaviour change and cardiometabolic risk factors remains unknown.
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