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- Karlöf, Eva, et al.
(författare)
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Correlation of computed tomography with carotid plaque transcriptomes associates calcification with lesion-stabilization
- 2019
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Ingår i: Atherosclerosis. - Stockholm : ELSEVIER IRELAND LTD. - 0021-9150 .- 1879-1484. ; 288, s. 175-185
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: Unstable carotid atherosclerosis causes stroke, but methods to identify patients and lesions at risk are lacking. We recently found enrichment of genes associated with calcification in carotid plaques from asymptomatic patients. Here, we hypothesized that calcification represents a stabilising feature of plaques and investigated how macro-calcification, as estimated by computed tomography (CT), correlates with gene expression profiles in lesions. Methods: Plaque calcification was measured in pre-operative CT angiographies. Plaques were sorted into high- and low-calcified, profiled with microarrays, followed by bioinformatic analyses. Immunohistochemistry and qPCR were performed to evaluate the findings in plaques and arteries with medial calcification from chronic kidney disease patients. Results: Smooth muscle cell (SMC) markers were upregulated in high-calcified plaques and calcified plaques from symptomatic patients, whereas macrophage markers were downregulated. The most enriched processes in high-calcified plaques were related to SMCs and extracellular matrix (ECM) organization, while inflammation, lipid transport and chemokine signaling were repressed. These findings were confirmed in arteries with high medial calcification. Proteoglycan 4 (PRG4) was identified as the most upregulated gene in association with plaque calcification and found in the ECM, SMA+ and CD68+/TRAP + cells. Conclusions: Macro-calcification in carotid lesions correlated with a transcriptional profile typical for stable plaques, with altered SMC phenotype and ECM composition and repressed inflammation. PRG4, previously not described in atherosclerosis, was enriched in the calcified ECM and localized to activated macrophages and smooth muscle-like cells. This study strengthens the notion that assessment of calcification may aid evaluation of plaque phenotype and stroke risk.
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| 2. |
- Peacock, Rachel E., et al.
(författare)
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Associations between lipoprotein lipase gene polymorphisms and plasma correlations of lipids, lipoproteins and lipase activities in young myocardial infarction survivors and age-matched healthy individuals from Sweden
- 1992
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Ingår i: Atherosclerosis. - : Elsevier BV. - 1879-1484 .- 0021-9150. ; 97:2-3, s. 171-185
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Tidskriftsartikel (refereegranskat)abstract
- Association studies were carried out on a sample of 87 patients from Sweden who had survived a myocardial infarction (MI) at a young age and 93 age-matched healthy individuals, to compare the impact of polymorphisms (PvuII, HindIII and Serine447-Stop) at the lipoprotein lipase (LPL) gene locus on among-individual differences in plasma lipid traits and progression of atherosclerosis. Significant linkage disequilibrium was detected between any two of these polymorphisms, with the Stop447 allele being only found on the same chromosome as the rare alleles (no cutting sites) of the PvuII and HindIII polymorphisms. In the healthy individuals, weak associations were found between genotypes of the HindIII polymorphism and triglycerides and the PvuII polymorphism and high density lipoprotein cholesterol explaining 7.4% and 5.6% of sample variance (P = 0.03 and 0.09), respectively. No associations were found between these traits and genotypes of the Serine447-Stop substitution, and thus it is unlikely to be the cause of the associations seen with the PvuII and HindIII polymorphisms even though it truncates the enzyme amino acid sequence. The presence of the rare allele, H-, of the HindIII polymorphism was associated with a smaller variance in triglycerides and both cholesterol and triglycerides in the very low density lipoprotein fraction, and with larger interdependent variation between these lipid traits, and also between LPL activity and these lipid traits. This implies that the H- allele, rather than the Stop447 allele, has the major impact on interdependence between traits which are directly or indirectly influenced by LPL activity. In the healthy individuals who were carriers of the apolipoprotein E2 allele, the inter-dependence between LPL activity and lipid traits was significantly smaller, and that between high density lipoprotein cholesterol and both cholesterol and triglycerides in the very low density lipoprotein fraction was much larger compared with non-carriers (P < 0.05). No significant associations were found between lipid traits or lipase activity and genotypes of the Serine447-Stop substitution. However, in the patients, global severity of coronary atherosclerosis at the first angiography was significantly associated with haplotype combinations of the HindIII and the Serine447-Stop polymorphisms, with the H-Stop haplotype being associated with the highest median score (P = 0.02). The data suggest that variation at the LPL gene locus is associated with a pleiotropic effect, that is not directly mediated by changes in lipids, on severity of coronary atherosclerosis.
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| 3. |
- Quensel, M, et al.
(författare)
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High density lipoprotein concentrations after cessation of smoking: the importance of alterations in diet
- 1989
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Ingår i: Atherosclerosis. - : Elsevier BV. - 1879-1484 .- 0021-9150. ; 75:2-3, s. 189-193
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Tidskriftsartikel (refereegranskat)abstract
- Cessation of smoking is followed by a rapid rise in plasma HDL concentrations. An earlier study has demonstrated a significant relationship between the increase in HDL concentrations and spontaneous changes in food intake, specifically an increased fat intake. In this investigation we have dissociated the effects of cessation of smoking as such from those of dietary alterations by monitoring plasma lipid and lipoprotein concentrations after cessation of smoking in 12 subjects whose diet was kept constant during an initial 2-week control period and during 2 weeks following cessation of smoking. Under these conditions plasma HDL-cholesterol levels did not increase significantly (1.01 +/- 0.26 mmol/l (mean +/- SD) before and 1.04 +/- 0.27 mmol/l after cessation of smoking). Similarly, no significant alterations were recorded for other plasma lipid or lipoprotein concentrations. Activities of lipoprotein lipase and hepatic lipase were unchanged throughout the study. These results suggest that the marked rise in HDL concentrations after stopping smoking is largely related to spontaneous changes in dietary habits which occur upon cessation of smoking.
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| 4. |
- Tornvall, P, et al.
(författare)
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Autoantibodies against modified low-density lipoproteins in coronary artery disease
- 2003
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Ingår i: Atherosclerosis. - 1879-1484 .- 0021-9150. ; 167:2, s. 347-353
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To evaluate the importance of different autoantibodies against modified low-density lipoprotein (LDL) in patients with coronary artery disease (CAD). Background: Previous studies of autoantibodies against LDL have shown that patients with CAD have increased titers of autoantibodies against LDL modified by copper and malondialdehyde (MDA), whereas there is a lack of information about autoantibody titers against LDL modified by hypochlorite (HOCl). Studies of autoantibodies in relation to severity of atherosclerosis are few and have reached divergent results. Furthermore, no data exist on the relationship between autoantibody titers and prognosis. Methods: Titers of autoantibodies against copper-, MDA- and HOCl-modified LDL were determined in serum by ELISA. Autoantibody titers in young male survivors of a first myocardial infarction were compared with those of healthy controls and related to coronary angiographic findings and to prognosis during I I years of follow-up. Results: Patients had higher titers of autoantibodies against LDL modified by copper and MDA than controls. In contrast, no consistent associations were found between autoantibody titers and global severity of coronary atherosclerosis or number and severity of coronary stenoses and prognosis. Conclusions: The prognostic value of autoantibodies against modified LDL is limited in young postinfarction patients despite the fact that autoantibody titers against copper- and NIDA-modified LDL are raised compared with healthy controls. Furthermore, the results indicate that autoantibodies against modified LDL are not protective in later stages of coronary atherosclerosis. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.
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