Anticytomegalovirus CD4
            +
            T Cells Are Associated With Subclinical Atherosclerosis in Persons With HIV

Objective: Persons with HIV have double the risk of developing cardiovascular disease compared with the general population. A persistent and heightened immune response to cytomegalovirus coinfection may be one contributing factor, but the relationship between cytomegalovirus replication, virus-specific immune cells, and plaque burden is unclear. Approach and Results: We assessed the relationship between CD4 + T-cell subsets and carotid plaque burden in a cohort of 70 HIV-positive participants with sustained viral suppression on a single antiretroviral regimen and without known cardiovascular disease. We evaluated relationships between immune parameters, carotid plaque burden, and brachial artery flow-mediated vasodilation using multivariable linear and logistic regression models. We found that participants with carotid plaque had increased circulating CX3CR1 + ~GPR56 + ~CD57 + (ie, C~G~C) + CD4 + T cells ( P =0.03), which is a marker combination associated with antiviral and cytotoxic responses. In addition, a median of 14.4% (IQR, 4.7%–32.7%) of the C~G~C + CD4 + T-cells expressed antigen receptors that recognized a single cytomegalovirus glycoprotein-B epitope. Using immunofluorescence staining, we found that CX3CR1 + CD4 + T cells were present in coronary plaque from deceased HIV-positive persons. C~G~C + CD4 + T cells were also present in cells isolated from the aorta of HIV-negative donors. Conclusions: HIV-positive persons with carotid atheroma have a higher proportion of circulating CD4 + T-cells expressing the C~G~C surface marker combination associated with antiviral and cytotoxic responses. These cells can be cytomegalovirus-specific and are also present in the aorta.

Download Full-text

Type 2 diabetic patients with diabetic retinopathy without previous cardiovascular disease show an increased carotid plaque burden

Atherosclerosis ◽

10.1016/j.atherosclerosis.2014.05.725 ◽

2014 ◽

Vol 235 (2) ◽

pp. e243

Author(s):

N. Alonso ◽

A. Traveset ◽

E. Rubinat ◽

M.V. Arcidiacono ◽

E. Ortega ◽

...

Keyword(s):

Cardiovascular Disease ◽

Diabetic Retinopathy ◽

Carotid Plaque ◽

Plaque Burden ◽

Diabetic Patients ◽

Type 2 Diabetic Patients ◽

Type 2 Diabetic

Download Full-text

1145Obesity-related changes in metabolomic profiles in youth

International Journal of Epidemiology ◽

10.1093/ije/dyab168.416 ◽

2021 ◽

Vol 50 (Supplement_1) ◽

Author(s):

Toby Mansell ◽

Matthew Sabin ◽

Zoe McCallum ◽

Markus Juonala ◽

David Burgner ◽

...

Keyword(s):

Cardiovascular Disease ◽

Subclinical Atherosclerosis ◽

Intima Media Thickness ◽

Carotid Intima Media Thickness ◽

Childhood And Adolescence ◽

Metabolic Dysfunction ◽

Metabolomic Profile ◽

Early Effect ◽

Analogous Data ◽

The Relationship

Abstract Background Obesity during childhood and adolescence is linked to subclinical atherosclerosis, metabolic dysfunction and later cardiovascular disease. Adults with obesity have metabolomic profiles that predict cardiovascular disease and mortality. Analogous data from children with obesity are sparse. Here, we aimed to investigate i) the relationship between the severity of obesity (determined by the percentage above the 95th BMI-centile (%>95th BMI-centile)) and metabolomic profiles, ii) the effect of changes in the severity of obesity on the metabolomic profile and iii) the relationship between obesity-related metabolites and subclinical atherosclerosis outcomes. Methods Participants from the Childhood Overweight Biorepository of Australia (COBRA) cohort had %>95th BMI-centile and NMR metabolomic profile (Nightingale, Finland) from fasted blood analysed at two time-points (mean interval of 5.5 years). At the follow-up visit, subclinical atherosclerosis phenotypes (carotid elasticity, carotid intima-media thickness, and pulse-wave velocity) were assessed. Results There were 98 participants who attended both visit 1 (mean %>95th BMI-centile 134.6±19.0) and visit 2 (mean %>95th BMI-centile 130.7±26.2). Higher absolute, and increasing severity, of obesity between visits were associated with increased phenylalanine, tyrosine, GlycA (a marker of chronic inflammation), and pyruvate, in both sexes (estimated increases of 0.14-0.18 standard deviations per 10% BMI-centile at visit 2, and 0.15-0.25 per 10% increase in BMI-centile between visits). There was modest evidence for a relationship between lower alanine and higher carotid elasticity. Conclusions In children with obesity, the overall severity of obesity and changes in obesity severity were associated with a metabolomic pattern that in adults is predictive of cardiovascular disease. In children, these metabolites were not related subclinical atherosclerosis; these relationships may become manifest with increasing age. Key messages There is evidence for an early effect of severe obesity on metabolomic profiles in childhood and adolescence.

Download Full-text

OP-140 [AJC » Treatment of Obesity and Diet in Cardiovascular Disease] Investigation of the Relationship Between Asthma and Subclinical Atherosclerosis by Carotid/Femoral Intima Media and Epicardial Fat Thickness Measurement

The American Journal of Cardiology ◽

10.1016/j.amjcard.2017.03.124 ◽

2017 ◽

Vol 119 (8) ◽

pp. e37

Author(s):

Mustafa Yılmaz ◽

Eylül Bozkurt Yılmaz ◽

Nazan Şen ◽

Cihan Altın ◽

Haldun Müderrisoğlu

Keyword(s):

Cardiovascular Disease ◽

Subclinical Atherosclerosis ◽

Thickness Measurement ◽

Epicardial Fat ◽

Epicardial Fat Thickness ◽

Fat Thickness ◽

Treatment Of Obesity ◽

The Relationship

Download Full-text

Carotid Plaque Burden as a Measure of Subclinical Atherosclerosis

JACC Cardiovascular Imaging ◽

10.1016/j.jcmg.2012.03.013 ◽

2012 ◽

Vol 5 (7) ◽

pp. 681-689 ◽

Cited By ~ 160

Author(s):

Henrik Sillesen ◽

Pieter Muntendam ◽

Aram Adourian ◽

Robert Entrekin ◽

Mario Garcia ◽

...

Keyword(s):

Carotid Plaque ◽

Subclinical Atherosclerosis ◽

Plaque Burden

Download Full-text

T Cell Immunosenescence in Aging, Obesity, and Cardiovascular Disease

Cells ◽

10.3390/cells10092435 ◽

2021 ◽

Vol 10 (9) ◽

pp. 2435

Author(s):

Kohsuke Shirakawa ◽

Motoaki Sano

Keyword(s):

Cardiovascular Disease ◽

T Cells ◽

T Cell ◽

Animal Studies ◽

Immune Cell ◽

Cardiovascular Risks ◽

Cell Network ◽

Adaptive Immune Cells ◽

Cell Changes ◽

The Relationship

Although advances in preventive medicine have greatly improved prognosis, cardiovascular disease (CVD) remains the leading cause of death worldwide. This clearly indicates that there remain residual cardiovascular risks that have not been targeted by conventional therapies. The results of multiple animal studies and clinical trials clearly indicate that inflammation is the most important residual risk and a potential target for CVD prevention. The immune cell network is intricately regulated to maintain homeostasis. Ageing associated changes to the immune system occurs in both innate and adaptive immune cells, however T cells are most susceptible to this process. T-cell changes due to thymic degeneration and homeostatic proliferation, metabolic abnormalities, telomere length shortening, and epigenetic changes associated with aging and obesity may not only reduce normal immune function, but also induce inflammatory tendencies, a process referred to as immunosenescence. Since the disruption of biological homeostasis by T cell immunosenescence is closely related to the development and progression of CVD via inflammation, senescent T cells are attracting attention as a new therapeutic target. In this review, we discuss the relationship between CVD and T cell immunosenescence associated with aging and obesity.

Download Full-text

miR-33 Silencing Reprograms the Immune Cell Landscape in Atherosclerotic Plaques

Circulation Research ◽

10.1161/circresaha.120.317914 ◽

2021 ◽

Author(s):

Milessa Silva Afonso ◽

Monika Sharma ◽

Martin Paul Schlegel ◽

Coen van Solingen ◽

Graeme J Koelwyn ◽

...

Keyword(s):

T Cells ◽

Lipid Metabolism ◽

Energy Homeostasis ◽

Target Genes ◽

Immune Cell ◽

Dynamic Balance ◽

T Cell Subsets ◽

Plaque Burden ◽

Atherosclerotic Plaques ◽

Plaque Inflammation

Rationale: MicroRNA-33 post-transcriptionally represses genes involved in lipid metabolism and energy homeostasis. Targeted inhibition of miR-33 increases plasma HDL cholesterol and promotes atherosclerosis regression, in part, by enhancing reverse cholesterol transport and dampening plaque inflammation. However, how miR-33 reshapes the immune microenvironment of plaques remains poorly understood. Objective: To define how miR-33 inhibition alters the dynamic balance and transcriptional landscape of immune cells in atherosclerotic plaques. Methods and Results: We used single cell RNA-sequencing of aortic CD45 + cells, combined with immunohistologic, morphometric and flow cytometric analyses to define the changes in plaque immune cell composition, gene expression and function following miR-33 inhibition. We report that anti-miR-33 treatment of Ldlr -/- mice with advanced atherosclerosis reduced plaque burden and altered the plaque immune cell landscape by shifting the balance of pro- and anti-atherosclerotic macrophage and T cell subsets. By quantifying the kinetic processes that determine plaque macrophage burden, we found that anti-miR-33 reduced levels of circulating monocytes and splenic myeloid progenitors, decreased macrophage proliferation and retention, and promoted macrophage attrition by apoptosis and efferocytotic clearance. scRNA-sequencing of aortic arch plaques showed that anti-miR-33 reduced the frequency of MHCIIhi "inflammatory" and Trem2hi "metabolic" macrophages, but not tissue resident macrophages. Furthermore, anti-miR-33 led to derepression of distinct miR-33 target genes in the different macrophage subsets: in resident and Trem2hi macrophages, anti-miR-33 relieved repression of miR-33 target genes involved in lipid metabolism (e.g., Abca1, Ncoa1, Ncoa2, Crot), whereas in MHCIIhi macrophages, anti-miR-33 upregulated target genes involved in chromatin remodeling and transcriptional regulation. Anti-miR-33 also reduced the accumulation of aortic CD8+ T cells and CD4+ Th1 cells, and increased levels of FoxP3+ regulatory T cells in plaques, consistent with an immune-dampening effect on plaque inflammation. Conclusions: Our results provide insight into the immune mechanisms and cellular players that execute anti-miR-33's atheroprotective actions in the plaque.

Download Full-text

P1535Clinical impact of carotid plaque score rather than carotid intima-media thickness on atherosclerotic cardiovascular disease

European Heart Journal ◽

10.1093/eurheartj/ehz748.0297 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

H Tada ◽

T Nakagawa ◽

H Okada ◽

T Nakahashi ◽

M Mori ◽

...

Keyword(s):

Risk Factors ◽

Cardiovascular Disease ◽

Carotid Plaque ◽

Intima Media Thickness ◽

Carotid Intima Media Thickness ◽

Plaque Burden ◽

Atherosclerotic Cardiovascular Disease ◽

Plaque Score ◽

Media Thickness

Abstract Background Carotid intima-media thickness (cIMT) assessed by ultrasound has been widely accepted as a surrogate marker of atherosclerotic cardiovascular disease. On the other hand, carotid plaque score (cPS) reflecting throughout the carotid artery plaque burden may be better marker. Methods We retrospectively examined 2,035 patients who underwent carotid ultrasonography between January 2006 and December 2015 at our University Hospital. Median follow-up period was 4 years. We used Cox models that adjusted for established risk factors of ASCVD, including age, gender, hypertension, diabetes, smoking, and serum lipids to assess the association of cIMT as well as cPS with major adverse cardiac events (MACE). MACE was defined as all-cause mortality or rehospitalization for a cardiovascular-related illness Results During follow-up, 243 participants experienced MACE. After adjustment for established risk factors, cPS was associated with MACE (hazard ratio [HR] = 3.38 for top quintile vs. bottom quintile of cPS; 95% confidence interval [CI] 1.82 to 6.27; P-trend = 1.4×10–8), while cIMT was not (HR = 0.88, P=0.57). Addition of the cPS to established risk factors significantly improved risk discrimination (C-index 0.726 vs. 0.746; P=0.017) Conclusion As a marker, cPS, rather than cIMT can identify 20% of individuals who are at more than three-fold increased risk for MACE. Targeting diagnostic or therapeutic interventions to this subset may prove clinically useful.

Download Full-text

Abstract P361: Inflammatory Burden May Partially Mediate the Relationship Between Everyday Discrimination and Carotid Plaque Height in Midlife Women

Circulation ◽

10.1161/circ.137.suppl_1.p361 ◽

2018 ◽

Vol 137 (suppl_1) ◽

Author(s):

Natalie Suder Egnot ◽

Emma Barinas-Mitchell ◽

Trevor Orchard ◽

Christina Wassel ◽

Maria Brooks ◽

...

Keyword(s):

Cardiovascular Disease ◽

Ethnic Groups ◽

Carotid Plaque ◽

Carotid Atherosclerosis ◽

Perceived Discrimination ◽

Midlife Women ◽

The Relationship ◽

Racial Ethnic ◽

Everyday Discrimination ◽

Inflammatory Burden

Introduction: Self-reported experiences of discrimination have been associated with greater risk of incident cardiovascular events and all-cause mortality across racial/ethnic groups. However, questions remain regarding the potential mechanisms through which perceived discrimination may influence cardiovascular risk. Furthermore, the relationship between self-reported discrimination with markers of subclinical cardiovascular disease (CVD) such as atherosclerotic plaque presence, burden, and characteristics remains unclear. We hypothesized that perceived discrimination is associated with subclinical measures of carotid atherosclerosis indicative of greater CVD risk and that inflammation is a mechanism contributing to this relationship. Methods: Late peri- and postmenopausal women without clinical CVD (n=300) completed the Everyday Discrimination Scale, developed in order to assess day-to-day experiences of interpersonal mistreatment, and underwent B-mode ultrasound to assess carotid atherosclerosis. Associations between everyday discrimination and measures of carotid plaque presence, burden (total number of plaques, total plaque area), and characteristics (maximum height, grey-scale median, and calcification) were evaluated using linear and logistic regression models adjusted for demographics, as well as CVD and psychosocial risk factors. Overall circulating inflammatory burden, comprising C-reactive protein, interleukin-6, and fibrinogen was identified via exploratory factor analysis and was evaluated as a potential mediator of the relationship between everyday discrimination and subclinical CVD through the ratio of the natural indirect effect and the total effect by inverse probability weighting. Results: The sample was predominately white (72% white (n=216); 22% black (n=66)), nearly half the women (n=138) had at least one carotid plaque, and 40% (n=120) reported experiencing high levels of everyday discrimination. After adjustment, women who reported high levels of discrimination had a maximum carotid plaque height 0.29 mm higher (p=0.03) than those who reported lower levels of discrimination. Circulating inflammatory burden was identified as a partial mediator of the relationship between high discrimination and carotid plaque height explaining 31% of the relationship. There were no significant associations of plaque presence, burden, or other plaque characteristics with discrimination, and the results did not vary by race/ethnicity. Conclusions: These findings add to the growing evidence that perceived discrimination may be associated with elevated cardiovascular disease risk among women of various racial/ethnic groups. These results suggest that increased inflammatory burden may be a mechanism through which experiences of discrimination may be associated with the development of atherosclerosis in midlife women.

Download Full-text