| 1. |
- Garvin, Peter, 1976-
(författare)
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Plasma levels of matrix metalloproteinase‐9 in a normal population : a psychoneuroendocrinological approach
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Several large‐scale epidemiological studies have demonstrated the prognostic significance of psychosocial factors and stress for coronary artery disease (CAD). Observations of sudden changes in CAD incidence have led to the proposal of mechanisms regarding atherosclerotic plaque vulnerability. The collagen‐degrading enzyme matrix metalloproteinase-9 (MMP-9) is increased in rupture‐prone plaques with high inflammatory activity, and circulating levels of MMP-9 are raised in patients with acute coronary syndrome. However, the distribution of MMP‐9 levels and its relations to psychosocial factors and the stress hormone cortisol have not been previously explored in a normal population.The aim of this dissertation was to examine in a normal population the association of circulating levels of MMP-9 with traditional cardiovascular risk factors including levels of C-reactive protein (CRP), with psychosocial factors, and with saliva levels of cortisol. In addition, the reliability of a new method of ambulatory saliva sampling for assessment of cortisol levels was evaluated. A sub‐sample of the Life conditions, Stress, and Health (LSH)-study, a population based study exploring psychoneuroendocrinological pathways mediating the differences in CAD incidence over socioeconomic status, was used. Plasma levels of MMP-9 were examined in a sample randomly drawn from the LSH‐study (n=400), aged 45 to 69 years at enrollment.The main findings were: 1) there was a positive association between plasma MMP-9 levels and total risk load of cardiovascular risk factors. The findings were persistent after adjusting for CRP and could not be attributed to a single risk factor. 2) After adjusting for traditional cardiovascular risk factors and CRP, MMP-9 levels were positively associated with psychosocial risk factors and negatively associated with psychosocial resources. 3) Pooling saliva samples prior to laboratory analysis were as reliable as arithmetic means for assessment of diurnal cortisol variation in a field research setting. 4) There was a positive association between circulating levels of MMP‐9 and saliva levels of cortisol, both diurnal peak level and evening level of cortisol. The observed associations between MMP‐9 and traditional cardiovascular risk factors, psychosocial factors, and saliva cortisol levels suggest a psychoneuroendocrinological pathway linking stress to plaque vulnerability and provide increased understanding of the association between psychosocial factors and CAD.
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| 2. |
- af Geijerstam, Peder, Doktorand, 1983-, et al.
(författare)
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P-selectin and C-reactive protein in relation to home blood pressure and coronary calcification: a SCAPIS substudy
- 2024
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Ingår i: Journal of Hypertension. - : Lippincott Williams & Wilkins. - 0263-6352 .- 1473-5598.
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Tidskriftsartikel (refereegranskat)abstract
- Background: Soluble P-selectin (sP-selectin) and high-sensitivity C-reactive protein (hsCRP) have previously been associated with hypertension, but the relation with out-of-office blood pressure (BP) and coronary artery calcification score is unknown. We aimed to examine the relationship between sP-selectin, hsCRP and home BP, as well as coronary artery calcification score and carotid artery plaques.Methods: In the Swedish CArdioPulmonary bioImage Study (SCAPIS), 5057 randomly selected participants were evaluated with office and home BP using the semi-automatic Omron M10-IT device. For this cross-sectional study, participants with sP-selectin <4 standard deviations above mean and hsCRP <5 mg/l, representing low-grade inflammation, were included. Using generalized linear models, these inflammatory markers were evaluated in relation to BP classifications, as well as coronary artery calcification score and carotid artery plaques.Results: Of participants, 4548 were included in the analyses. The median age was 57.2 (53.4–61.2) years, and 775 (17.0%) reported taking medication for hypertension. Participants in the highest quartile of sP-selectin [odds ratio (OR) 1.67, 95% confidence interval (CI) 1.40–1.98, P < 0.001] and hsCRP [OR 2.25, (95% CI 1.89–2.60), P < 0.001] were more likely to have sustained hypertension. Participants in the highest quartile of hsCRP were also more likely to have masked hypertension, OR (95% CI) 2.31 (1.72–3.10), P < 0.001 and carotid artery plaques, OR (95% CI) 1.21 (1.05–1.38), P = 0.007.Conclusion: Increased sP-selectin and hsCRP were independently associated with sustained hypertension. These findings indicate an association between hypertension and platelet activity, as expressed by sP-selectin.
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| 3. |
- Alfredsson, Joakim, et al.
(författare)
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Individual long-term variation of platelet reactivity in patients with dual antiplatelet therapy after myocardial infarction.
- 2019
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Ingår i: Platelets. - : Informa UK Limited. - 0953-7104 .- 1369-1635. ; 30:5, s. 572-578
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Tidskriftsartikel (refereegranskat)abstract
- There is a large inter-individual variation in response to clopidogrel treatment, and previous studies have indicated higher risk of thrombotic events in those with high residual platelet reactivity (HPR). Less is known about individual variation over time. The aim of this prospective cohort study was to investigate intra-individual variation in platelet reactivity. Platelet aggregation in whole blood was assessed in 77 patients, at 3 days, 8 days and 6 months after admission for acute myocardial infarction and loading dose of clopidogrel. All patients were treated with aspirin and clopidogrel through 6-month follow-up. We found a significant increase in median ADP-stimulated aggregation from third to eighth day (195 vs. 250 AU*min, p-value = 0.001) but not from day 8 to 6 months (250 vs. 223 AU*min, p-value = 0.666). There was no significant change in the overall rate of HPR (15.6% vs 20.8%, p-value 0.503) or low platelet reactivity (LPR) (37.7% vs 33.8%, p-value = 0.609) from day 8 to 6-month follow-up. In contrast, more than one in four changed HPR status, 15.6% from non-HPR to HPR and 10.4% HPR to non-HPR. A shift in LPR status appeared even more frequent, occurring in about one of three patients. In spite of similar median aggregation and rate of HPR during 6-month follow-up, about one in four of the patients changed HPR status and one in three changed LPR status. This may be important information for a concept of risk stratification based on a single aggregation value early after an acute coronary syndromes.
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| 4. |
- Alfredsson, Joakim, et al.
(författare)
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Large early variation of residual platelet reactivity in Acute Coronary Syndrome patients treated with clopidogrel : Results from Assessing Platelet Activity in Coronary Heart Disease (APACHE).
- 2015
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Ingår i: Thrombosis Research. - : Pergamon Press. - 0049-3848 .- 1879-2472. ; 136:2, s. 335-340
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: There is a large inter-individual variation in response to clopidogrel treatment and previous studies have indicated higher risk of thrombotic events in patients with high residual platelet reactivity (HRPR), but the optimal time-point for testing is not established. The aim of this study was to investigate the optimal time-point for aggregometry testing and the risk of major adverse cardiac events associated with HRPR.METHOD AND RESULTS: We included 125 patients with ACS (73 with STEMI, and 71 received abciximab). The prevalence of HRPR varied substantially over time. The rate of HRPR in patients treated and not treated with abciximab were 43% vs 67% (p=0.01) before, 2% vs 23% (p=0.001) 6-8h after, 8% vs 9% (p=0.749) 3days after, and 23% vs 12% (p=0.138) 7-9 days after loading dose of clopidogrel. We found HRPR in 18% of the patients but only four ischemic events during 6months follow-up, with no significant difference between HRPR patients compared to the rest of the population. There were 3 TIMI major bleedings, all of which occurred in the low residual platelet reactivity (LRPR) group.CONCLUSION: There is a large variation in platelet reactivity over time, also depending on adjunctive therapy, which has a large impact on optimal time-point for assessment. We found HRPR in almost 1 in 5 patients, but very few MACE, and not significantly higher in HRPR patients. In a contemporary ACS population, with low risk for stent thrombosis, the predictive value of HRPR for ischemic events will probably be low.
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| 6. |
- Andresen, Louise C., et al.
(författare)
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Seasonal changes in nitrogen availability, and root and microbial uptake of (15)N(13)C(9)-phenylalanine and (15)N-ammonium in situ at a temperate heath
- 2011
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Ingår i: Applied Soil Ecology. - : Elsevier BV. - 0929-1393. ; 51, s. 94-101
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Tidskriftsartikel (refereegranskat)abstract
- In the plant biosynthesis of secondary compounds, phenylalanine is a precursor of condensed tannins. Tannins are deposited into the soil in plant root exudates and dead plant material and have been suggested to precipitate some soil nutrients and hence reduce nutrient availability for plants. Free amino acid, inorganic and microbial N concentration during the growing season was investigated in an ecosystem with a natural tannin chemosphere. The influence of tannins on the uptake of nitrogen in plants and microbes was followed by injecting tannic acid (TA), ammonium-(15)N and phenylalanine-(15)N/(13)C(9). Plants preferred ammonium over phenylalanine, while microbes had no preference. Soil microbes had a 77% uptake of intact phenylalanine. Phenylalanine was acquired intact by both grasses and Calluna, with 63% and 38% uptake of intact phenylalanine in grass fine roots and Calluna roots, respectively. Inorganic N and amino acid concentrations were lowest in the period with highest plant activity and grass root biomass but were unaffected by TA addition. (C) 2011 Elsevier B.V. All rights reserved.
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| 7. |
- Andresen, Louise C., et al.
(författare)
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Uptake of pulse injected nitrogen by soil microbes and mycorrhizal and non-mycorrhizal plants in a species-diverse subarctic heath ecosystem
- 2008
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Ingår i: Plant and Soil. - : Springer Science and Business Media LLC. - 0032-079X .- 1573-5036. ; 313:1-2, s. 283-295
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Tidskriftsartikel (refereegranskat)abstract
- N-15 labeled ammonium, glycine or glutamic acid was injected into subarctic heath soil in situ, with the purpose of investigating how the nitrogen added in these pulses was subsequently utilized and cycled in the ecosystem. We analyzed the acquisition of N-15 label in mycorrhizal and non-mycorrhizal plants and in soil microorganisms, in order to reveal probable differences in acquisition patterns between the two functional plant types and between plants and soil microorganisms. Three weeks after the label addition, with the N-15-forms added with same amount of nitrogen per square meter, we analyzed the N-15-enrichment in total soil, in soil K2SO4 (0.5 M) extracts and in the microbial biomass after vacuum-incubation of soil in chloroform and subsequent K2SO4 extraction. Furthermore the N-15-enrichment was analyzed in current years leaves of the dominant plant species sampled three, five and 21 days after label addition. The soil microorganisms had very high N-15 recovery from all the N sources compared to plants. Microorganisms incorporated most N-15 from the glutamic acid source, intermediate amounts of N-15 from the glycine source and least N-15 from the NH4+ source. In contrast to microorganisms, all ten investigated plant species generally acquired more N-15 label from the NH4+ source than from the amino acid sources. Non-mycorrhizal plant species showed higher concentration of N-15 label than mycorrhizal plant species 3 days after labeling, while 21 days after labeling their acquisition of N-15 label from amino acid injection was lower than, and the acquisition of N-15 label from NH4 injection was similar to that of the mycorrhizal species. We conclude that the soil microorganisms were more efficient than plants in acquiring pulses of nutrients which, under natural conditions, occur after e. g. freeze-thaw and dry rewet events, although of smaller size. It also appears that the mycorrhizal plants in the short term may be less efficient than non-mycorrhizal plants in nitrogen acquisition, but in a longer term show larger nitrogen acquisition than non-mycorrhizal plants. However, the differences in N-15 uptake patterns may also be due to differences in leaf longevity and woodiness between plant functional groups.
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| 8. |
- Backteman, Karin, et al.
(författare)
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Cytomegalovirus seropositivity is a major determinant of CD28null T cell expansion in patients with coronary artery disease
- 2014
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Objective: Accumulation of CD4+28null cells, with a proinflammatory and senescent phenotype, has been associated with unstable conditions of coronary artery disease (CAD). Human cytomegalovirus (HCMV) is known to exert profound effects on T cells, including loss of CD28. Here, we longitudinally assessed the proportions of CD28null and CD28nullCD57+ cells in CD4+ and CD8+ T cell populations of patients with CAD and related the findings to HCMV seropositivity.Methods: HCMV antibody levels and expression of CD28 and CD57 on CD4+ and CD8+ T cells were analysed in 31 patients with acute coronary syndrome (ACS), 34 patients with stable angina (SA) and 37 healthy controls. Samples were taken prior to 34 coronary angiography and after 3 and 12 months. In a subsample, HCMV-specific IFN-γ and TNF production was assessed ex vivo.Results: Increased proportions of CD4+CD28null, but not CD8+CD28null cells, were significantly associated with presence of CAD. Significant increases in CD28null 37 and CD28nullCD57+ cells occurred within CD4+ and CD8+ T cell compartments in both ACS and SA patients during 12-month follow-up. HCMV was the major determinant of CD28null and CD28nullCD57+ T cell levels in both patients and controls (p <0.001). There were no obvious signs of CMV reactivation in patients.Conclusion: HCMV was a major determinant of the presence of CD28null and CD28nullCD57+ T cells in patients with CAD, independent of clinical stage. Findings also indicate that HCMV might have a large impact on the T cell aging process that occurred in patients after a cardiac event.
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| 9. |
- Backteman, Karin, et al.
(författare)
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Lymphocyte Subpopulations in Lymph Nodes and Peripheral Blood: A Comparison between Patients with Stable Angina and Acute Coronary Syndrome
- 2012
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 7:3
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Atherosclerosis is characterized by a chronic inflammatory response involving activated T cells and impairment of natural killer (NK) cells. An increased T cell activity has been associated with plaque instability and risk of acute cardiac events. Lymphocyte analyses in blood are widely used to evaluate the immune status. However, peripheral blood contains only a minor proportion of lymphocytes. In this study, we hypothesized that thoracic lymph nodes from patients with stable angina (SA) and acute coronary syndrome (ACS) might add information to peripheral blood analyses. less thanbrgreater than less thanbrgreater thanMethods: Peripheral blood and lymph nodes were collected during coronary by-pass surgery in 13 patients with SA and 13 patients with ACS. Lymphocyte subpopulations were assessed by flow cytometry using antibodies against CD3, CD4, CD8, CD19, CD16/56, CD25, Foxp3, CD69, HLA-DR, IL-18 receptor (R) and CCR4. less thanbrgreater than less thanbrgreater thanResults: Lymph nodes revealed a lymphocyte subpopulation profile substantially differing from that in blood including a higher proportion of B cells, lower proportions of CD8(+) T cells and NK cells and a 2-fold higher CD4/CD8 ratio. CD4(+)CD69(+) cells as well as Foxp3(+) regulatory T cells were markedly enriched in lymph nodes (p andlt; 0.001) while T helper 1-like (CD4(+)IL-18R(+)) cells were more frequent in blood (p andlt; 0.001). The only significant differences between ACS and SA patients involved NK cells that were reduced in the ACS group. However, despite being reduced, the NK cell fraction in ACS patients contained a significantly higher proportion of IL-18R(+) cells compared with SA patients (p andlt; 0.05). less thanbrgreater than less thanbrgreater thanConclusion: There were several differences in lymphocyte subpopulations between blood and lymph nodes. However, the lymphocyte perturbations in peripheral blood of ACS patients compared with SA patients were not mirrored in lymph nodes. The findings indicate that lymph node analyses in multivessel coronary artery disease may not reveal any major changes in the immune response that are not detectable in blood.
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