| 1. |
- Rattik, Sara, et al.
(författare)
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Elevated circulating effector memory T cells but similar levels of regulatory T cells in patients with type 2 diabetes mellitus and cardiovascular disease
- 2019
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Ingår i: Diabetes and Vascular Disease Research. - : SAGE Publications. - 1479-1641 .- 1752-8984. ; 16:3, s. 270-280
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Tidskriftsartikel (refereegranskat)abstract
- Type 2 diabetes mellitus is associated with an elevated risk of cardiovascular disease, but the mechanism through which diabetes contributes to cardiovascular disease development remains incompletely understood. In this study, we compared the association of circulating regulatory T cells, naïve T cells, effector memory T cells or central memory T cells with cardiovascular disease in patients with and without type 2 diabetes mellitus. Percentage of circulating T cell subsets was analysed by flow cytometry in type 2 diabetes mellitus subjects with and without prevalent cardiovascular disease as well as in non-diabetic subjects with and without prevalent cardiovascular disease from the Malmö SUMMIT cohort. Subjects with type 2 diabetes mellitus had elevated percentages of effector memory T cells (CD4+CD45RO+CD62L–; 21.8% ± 11.2% vs 17.0% ± 9.2% in non-type 2 diabetes mellitus, p < 0.01) and central memory T cells (CD4+CD45RO+CD62L+; 38.0% ± 10.7% vs 36.0% ± 9.5% in non-type 2 diabetes mellitus, p < 0.01). In contrast, the frequency of naïve T cells was reduced (CD4+CD45RO–CD62L+, 35.0% ± 16.5% vs 42.9% ± 14.4% in non-type 2 diabetes mellitus, p < 0.001). The proportion of effector memory T cells was increased in type 2 diabetes mellitus subjects with cardiovascular disease as compared to those without (26.4% ± 11.5% vs 18.4% ± 10.2%, p < 0.05), while no difference in regulatory T cells was observed between these two patient groups. This study identifies effector memory T cells as a potential cellular biomarker for cardiovascular disease among subjects with type 2 diabetes mellitus, suggesting a state of exacerbated immune activation in type 2 diabetes mellitus patients with cardiovascular disease.
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| 2. |
- Sveen, Kari Anne, et al.
(författare)
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High levels of autoantibodies against apoB100 p210 are associated with lower incidence of atrial fibrillation in women
- 2022
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 291:2, s. 207-217
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Tidskriftsartikel (refereegranskat)abstract
- Background and objectives Atrial fibrillation (AF) is associated with inflammation systemically and in the atrial tissue. Oxidized low-density lipoprotein (LDL) is increased in patients with AF and is suggested to be one of the molecules that drives inflammation. Autoantibodies against oxidized LDL and apolipoprotein B100, the protein component of LDL, are linked to atherosclerotic disease. However, whether these autoantibodies are associated with occurrence of AF is not known. We investigated autoantibodies against oxidized apolipoprotein B100 peptides and incidence of AF in a large population-based cohort. Methods IgM and IgG against native and aldehyde-modified apoB100 peptides 210 (p210) and 45 were analyzed by enzyme-linked immunosorbent assay (ELISA) in 5169 individuals from the Malmo Diet and Cancer cohort. Results Seven hundred sixty-nine incident AF cases were recorded during a follow-up of 21.3 years. Individuals with high levels of IgM against native p210 at baseline had a lower risk to develop AF; however, the association did not remain after adjustment for age and sex. Women had higher levels of IgM against native p210 than men (0.70 +/- 0.22 AU vs. 0.63 +/- 0.21 AU, p < 0.001). The association of IgM against native p210 and AF was significantly different between sexes (p for interaction = 0.024), where females with high IgM against p210 had a lower risk for incidence of AF (hazard ratio [95% confidence interval] 4th versus 1st quartile: 0.67 [0.49-0.91]; p = 0.01) after adjusting for risk factors and comorbidities. Conclusion These findings support an association of humoral autoimmunity with AF.
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| 3. |
- Wigren, Maria, et al.
(författare)
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Decreased levels of stem cell factor in subjects with incident coronary events
- 2016
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 279:2, s. 180-191
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: It has been proposed that vascular progenitor cells play an important role in vascular repair, but their possible clinical importance in cardiovascular disease has not been fully characterized. Vascular endothelial growth factor A, placental growth factor and stem cell factor (SCF) are three growth factors that are important in recruiting vascular progenitor cells. In this study, we investigated the association between the plasma levels of these growth factors and incident coronary events (CEs).METHODS: Levels of the three growth factors were measured using the proximity extension assay technique in baseline plasma samples from 384 subjects with a first CE (mean follow-up 14.0 ± 4.3 years) and 409 event-free control subjects matched by sex and age, as well as in homogenates from 201 endarterectomy specimens.RESULTS: After controlling for known cardiovascular disease risk factors in a Cox regression model, subjects in the lowest SCF tertile had a hazard ratio of 1.70 (95% confidence interval 1.14-2.54) compared with subjects in the highest SCF tertile. Lower SCF levels were also associated with more severe carotid disease, less fibrous atherosclerotic plaques and an increased incidence of heart failure. Expression of the SCF receptor c-kit was demonstrated in the subendothelial layer and fibrous cap of human atherosclerotic plaques. Smokers and subjects with diabetes had decreased levels of SCF compared with control subjects.CONCLUSION: To our knowledge, this is the first clinical study to provide evidence to support a key role for SCF and progenitor cells in vascular repair. We suggest that the SCF-c-kit pathway may be a promising biomarker and therapeutic target in cardiovascular disease.
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| 4. |
- Shore, Angela C, et al.
(författare)
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Use of Vascular Assessments and Novel Biomarkers to Predict Cardiovascular Events in Type 2 Diabetes : The SUMMIT VIP Study
- 2018
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Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 41:10, s. 2212-2219
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Cardiovascular disease (CVD) risk prediction represents an increasing clinical challenge in the treatment of diabetes. We used a panel of vascular imaging, functional assessments, and biomarkers reflecting different disease mechanisms to identify clinically useful markers of risk for cardiovascular (CV) events in subjects with type 2 diabetes (T2D) with or without manifest CVD.RESEARCH DESIGN AND METHODS: The study cohort consisted of 936 subjects with T2D recruited at four European centers. Carotid intima-media thickness and plaque area, ankle-brachial pressure index, arterial stiffness, endothelial function, and circulating biomarkers were analyzed at baseline, and CV events were monitored during a 3-year follow-up period.RESULTS: The CV event rate in subjects with T2D was higher in those with (n = 440) than in those without (n = 496) manifest CVD at baseline (5.53 vs. 2.15/100 life-years, P < 0.0001). New CV events in subjects with T2D with manifest CVD were associated with higher baseline levels of inflammatory biomarkers (interleukin 6, chemokine ligand 3, pentraxin 3, and hs-CRP) and endothelial mitogens (hepatocyte growth factor and vascular endothelial growth factor A), whereas CV events in subjects with T2D without manifest CVD were associated with more severe baseline atherosclerosis (median carotid plaque area 30.4 mm2 [16.1-92.2] vs. 19.5 mm2 [9.5-40.5], P = 0.01). Conventional risk factors, as well as measurements of arterial stiffness and endothelial reactivity, were not associated with CV events.CONCLUSIONS: Our observations demonstrate that markers of inflammation and endothelial stress reflect CV risk in subjects with T2D with manifest CVD, whereas the risk for CV events in subjects with T2D without manifest CVD is primarily related to the severity of atherosclerosis.
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| 5. |
- Georgakis, Marios K., et al.
(författare)
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Circulating Monocyte Chemoattractant Protein-1 and Risk of Stroke : Meta-Analysis of Population-Based Studies Involving 17 180 Individuals
- 2019
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Ingår i: Circulation Research. - 0009-7330. ; 125:8, s. 773-782
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: Proinflammatory cytokines have been identified as potential targets for lowering vascular risk. Experimental evidence and Mendelian randomization suggest a role of MCP-1 (monocyte chemoattractant protein-1) in atherosclerosis and stroke. However, data from large-scale observational studies are lacking. Objective: To determine whether circulating levels of MCP-1 are associated with risk of incident stroke in the general population. Methods and Results: We used previously unpublished data on 17 180 stroke-free individuals (mean age, 56.7±8.1 years; 48.8% men) from 6 population-based prospective cohort studies and explored associations between baseline circulating MCP-1 levels and risk of any stroke, ischemic stroke, and hemorrhagic stroke during a mean follow-up interval of 16.3 years (280 522 person-years at risk; 1435 incident stroke events). We applied Cox proportional-hazards models and pooled hazard ratios (HRs) using random-effects meta-analyses. After adjustments for age, sex, race, and vascular risk factors, higher MCP-1 levels were associated with increased risk of any stroke (HR per 1-SD increment in ln-transformed MCP-1, 1.07; 95% CI, 1.01-1.14). Focusing on stroke subtypes, we found a significant association between baseline MCP-1 levels and higher risk of ischemic stroke (HR, 1.11 [1.02-1.21]) but not hemorrhagic stroke (HR, 1.02 [0.82-1.29]). The results followed a dose-response pattern with a higher risk of ischemic stroke among individuals in the upper quartiles of MCP-1 levels as compared with the first quartile (HRs, second quartile: 1.19 [1.00-1.42]; third quartile: 1.35 [1.14-1.59]; fourth quartile: 1.38 [1.07-1.77]). There was no indication for heterogeneity across studies, and in a subsample of 4 studies (12 516 individuals), the risk estimates were stable after additional adjustments for circulating levels of IL (interleukin)-6 and high-sensitivity CRP (C-reactive protein). Conclusions: Higher circulating levels of MCP-1 are associated with increased long-term risk of stroke. Our findings along with genetic and experimental evidence suggest that MCP-1 signaling might represent a therapeutic target to lower stroke risk.Visual Overview: An online visual overview is available for this article.
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| 6. |
- Wigren, Maria, et al.
(författare)
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Low Levels of Circulating CD4+FoxP3+ T Cells Are Associated With an Increased Risk for Development of Myocardial Infarction But Not for Stroke.
- 2012
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Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - : Lippincott Williams & Wilkins. - 1524-4636 .- 1079-5642. ; 32:8, s. 2000-2007
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Regulatory T cells (Tregs) protect against atherosclerosis in experimental models, but their association with cardiovascular disease in humans remains to be elucidated. The aim of the present study was to determine whether circulating Tregs predict the development of acute cardiovascular events in humans. METHODS AND RESULTS: The study cohort consisted of a random sample of participants (n=700), aged 68 to 73 years, from the Malmo Diet and Cancer Study. Mononuclear leukocytes, stored at -140°C at the baseline investigation in 1991.1994, were thawed and Tregs, defined by the expression of FoxP3 in CD4+ T cells, were analyzed by flow cytometry. There was no detectable loss of cells during storage, and the viability of thawed leukocytes was 95%. A low fraction of both CD4+FoxP3+ and CD4+CD25+FoxP3+ T cells was associated with a higher release of proinflammatory cytokines from activated mononuclear leukocytes, and this association was strongest for CD4+FoxP3+ cells. Eighty-four coronary events and 66 strokes were registered during follow-up until December 31, 2008. In a Cox proportional hazard regression model adjusting for major risk factors, low levels of baseline CD4+FoxP3+ T cells were associated with an increased risk for the development of acute coronary events but not stroke. There were no associations between CD4+CD25+FoxP3+ T cells and development of an acute coronary event or stroke. CONCLUSIONS: This study provides prospective evidence for the role of Tregs in the development of myocardial infarction. The findings are in accordance with previous experimental studies and provide clinical support for a protective role of Tregs in atherosclerosis. The lack of association between Tregs and stroke may reflect the more heterogeneous cause of this disease.
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| 7. |
- Björkbacka, Harry, et al.
(författare)
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Weak associations between human leucocyte antigen genotype and acute myocardial infarction
- 2010
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Ingår i: Journal of Internal Medicine. - : Blackwell Publishing Ltd. - 0954-6820 .- 1365-2796. ; 268:1, s. 50-58
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Human leucocyte antigens (HLAs) are polymorphic molecules involved in antigen presentation. Associations between HLA type and autoimmune diseases, such as type 1 diabetes and rheumatoid arthritis, are well established but the potential association of genetic variation affecting antigen presentation with cardiovascular disease has not been systematically investigated in large cohorts. The importance of such studies is stressed by recent experimental findings of an involvement of autoimmunity in the atherosclerotic disease process. Results: An SSP-PCR method was used for HLA genotyping to determine associations of HLA-DRB1, -DQA1 and -DQB1 with cardiovascular disease in a population-based cohort of 1188 acute myocardial infarction (AMI) patients and 1191 matched healthy controls. The HLA-DRB1*0101 allele, as well as the HLA-DRB1*0101-DQA1*01-DQB1*05 haplotype, was found to be associated with increased risk for AMI (OR 1.24; 95% CI 1.00–1.54 for both). In contrast, the DRB1*07 and DQA*02 alleles (OR 0.78; 95% CI 0.65–0.95 for both), as well as the DRB1*07-DQA*02-DQB*02 haplotype, conferred protection (OR 0.79; 95% CI 0.63–0.98). An HLA risk score taking each individual’s both haplotypes into account was higher amongst cases (2.43 ± 0.92 vs. 2.29 ± 0.95, P = 0.001). The association between HLA risk score and AMI was independent of other cardiovascular riskfactors assessed. Conclusions: This study demonstrates that the associations between HLA-DRB1 and DQA1 loci and cardiovascular disease exists but that they are considerably weaker than those previously reported for other diseases with an established autoimmune aetiology such as type 1 diabetes, systemic lupus erythematosus and rheumatoid arthritis.
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| 8. |
- Berg, Katarina, et al.
(författare)
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Elevated CD14++CD16− Monocytes Predict Cardiovascular Events
- 2012
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Ingår i: Circulation. - : Lippincott Williams & Wilkins. - 1942-325X .- 1942-3268. ; 5:1, s. 122-131
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Tidskriftsartikel (refereegranskat)abstract
- Background—Although monocytes in peripheral blood are no longer considered to be a homogeneous population, associations between distinct monocyte subsets and cardiovascular disease have not been highlighted in large epidemiological studies. Methods and Results—The study included 700 randomly selected subjects from the cardiovascular arm of the Malmö Diet and Cancer study. Among these, 123 subjects experienced ischemic cardiovascular events during the follow-up until December 2008. Mononuclear leukocytes frozen at the baseline investigation in 1991 to 1994 were thawed and analyzed with flow cytometry to enumerate monocyte subsets, based on CD14 and CD16 expression. The percentage and number of classical CD14++CD16− monocytes were increased in the cardiovascular-event group compared with the event-free subjects (median, 69% [interquartile range, 62% to 76%] versus 67% [59% to 72%], P=0.017; 344 [251 to 419] cells/μL versus 297 [212 to 384] cells/μL, P=0.003). The hazard ratio was 1.66 for suffering a cardiovascular event in the highest tertile of the number of CD14++CD16− monocytes compared with the lowest tertile, even after adjustment for common risk factors (HR, 1.66; 95% CI: 1.02 to 2.72). CD14++CD16− monocytes did not, however, associate with the extent of atherosclerosis at baseline. In contrast, the percentage of monocytes expressing CD16 was negatively associated to the extent of carotid atherosclerosis measured as intima-media thickness at baseline. The chemokine receptors CCR2, CX3CR1, and CCR5 were not differentially expressed between cases and controls on any of the monocyte subsets, but CCR5 expression on CD14+CD16++ monocytes was negatively associated to carotid intima-media thickness. Conclusions—This study shows that classical CD14++CD16− monocytes can predict future cardiovascular risk independently of other risk factors in a randomly selected population.
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| 9. |
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| 10. |
- Grönberg, Caitríona, et al.
(författare)
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Endarterectomy patients with elevated levels of circulating IL-16 have fewer cardiovascular events during follow-up
- 2016
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Ingår i: Cytokine. - : Elsevier BV. - 1043-4666. ; 85, s. 137-139
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose Increased interleukin 16 (IL-16) levels in carotid plaques have been associated with reduced incidence of cardiovascular (CV) events during follow-up in patients who underwent carotid endarterectomy (CEA). In the present study we aimed to determine whether high circulating levels of IL-16 also are associated with a decreased risk of CV events after CEA. Methods Patients, who had their carotid plaques surgically removed (n = 473), were followed for a mean follow-up time of 3.1 years. Plasma levels of IL-16 the day before surgery were analyzed by proximity extension assay (PEA) and associated with the occurrence of CV events during follow-up (n = 98). Results High levels of circulating IL-16 were independently associated with a decreased risk of CV events when comparing the highest versus the lowest IL-16 tertile (hazard ratio [HR] 0.47; 95% CI 0.27–0.81; P = 0.007), as well as with CV deaths (HR 0.25; 95% CI 0.09–0.70; P = 0.008). Conclusion These present findings indicate an association between IL-16 and less clinical complications of atherosclerosis in a population with known advanced carotid disease.
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