| 1. |
- 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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| 5. |
- Carlson, Lars A., et al.
(författare)
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A case of massive hypertriglyceridemia corrected by nicotinic acid or nicotinamide therapy
- 1972
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Ingår i: Atherosclerosis. - : Elsevier BV. - 0021-9150 .- 1879-1484. ; 16:3, s. 359-368
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Tidskriftsartikel (refereegranskat)abstract
- A case of massive hypertriglyceridemia with fasting plasma triglycerides around 100 mmoles/l is described. Large amounts of chylomicra were present in fasting plasma and the amounts of low-density and high-density lipoproteins were very low. Postheparin plasma lipolytic activity was normal and intravenous heparin rapidly cleared the patient's abnormally prolonged alimentary lipemia with a concomitant rise in plasma free fatty acid levels.Nicotinic acid or nictotinamide given in doses of 3 g or more daily reduced plasma triglyceride levels to about 2–3 mmoles/1 and raised the reduced levels of low and high-density lipoproteins. The mode of onset of this therapeutic effect was slow and the effect persisted for several weeks after withdrawal of either nicotinic acid or nicotinamide.The pathogenesis of the hypertriglyceridemia as well as the mode of action of nicotinic acid and nicotinamide is discussed.
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| 6. |
- Carlson, Lars A., et al.
(författare)
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Effect of chlorophenoxyisobutyric acid (CPIB) on fat-mobilizing lipolysis and cyclic AMP levels in rat epididymal fat
- 1972
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Ingår i: Atherosclerosis. - : Elsevier BV. - 0021-9150 .- 1879-1484. ; 16:3, s. 349-357
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Tidskriftsartikel (refereegranskat)abstract
- High concentrations of chlorophenoxyisobutyric acid (CPIB) reduced basal glycerol release from rat epididymal fat pads in vitro and antagonized the lipolytic effects of noradrenaline. Furthermore, very high concentrations of CPIB significantly antagonized the effects or noradrenaline or ACTH on cyclic AMP accumulation by isolated rat adipocytes. These data are not incompatible with the hypothesis that a primary mechanism in the hypolipidemic action of CPIB is to lower the levels of cyclic AMP in adipose tissue, resulting in decreased hormone-sensitive lipase activity and/or increased lipoprotein lipase activity.
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| 7. |
- Eriksson, Jan, et al.
(författare)
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Postprandial regulation of blood lipids and adipose tissue lipoprotein lipase in type 2 diabetes patients and healthy control subjects
- 2003
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Ingår i: Atherosclerosis. - : Elsevier. - 0021-9150 .- 1879-1484. ; 166:2, s. 359-367
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Tidskriftsartikel (refereegranskat)abstract
- Background/aim: In type 2 diabetes and other insulin-resistant conditions, postprandial hypertriglyceridaemia is an important metabolic perturbation. To further elucidate alterations in the clearance of triglyceride-rich lipoproteins in type 2 diabetes we focused on the nutritional regulation of adipose tissue lipoprotein lipase (LPL).Subjects and methods: Eight subjects with type 2 diabetes and eight age-, sex- and body mass index (BMI)-matched control subjects underwent subcutaneous abdominal adipose tissue biopsies in the fasting state and 3.5 h following a standardized lipid-enriched meal. LPL activity and mass were measured in adipose tissue and also in plasma after an intravenous injection of heparin.Results: Postprandial, but not fasting, triglycerides were significantly higher in the diabetic subjects than in the control subjects (3.0±0.4 vs 2.0±0.2 mmol/l, P=0.028). Adipose tissue LPL activity was increased following the meal test by ∼35–55% (P=0.021 and 0.004, respectively). There was no significant difference between the groups in this respect. The specific enzyme activity of LPL was not altered in the postprandial state. Fasting and postprandial adipose tissue LPL activity as well as post-heparin plasma LPL activity tended to be lower among the diabetes patients (NS). There was a significant and independent inverse association between insulin resistance (homeostasis model assessment insulin resistance (HOMA-IR) index) vs post-heparin plasma LPL activity and postprandial triglyceride levels, respectively. Adipose tissue LPL activity was related to insulin action in vitro on adipocyte glucose transport, but not to HOMA-IR.Conclusion: Following food intake adipose tissue LPL activity is enhanced to a similar degree in patients with type 2 diabetes and in healthy control subjects matched for BMI, age and gender. If LPL dysregulation is involved in the postprandial hypertriglyceridaemia found in type 2 diabetes, it should occur in tissues other than subcutaneous fat.
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| 8. |
- Holmlund, A., et al.
(författare)
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Soluble intercellular adhesion molecule-1 is related to endothelial vasodilatory function in healthy individuals
- 2002
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Ingår i: Atherosclerosis. - 0021-9150 .- 1879-1484. ; 165:2, s. 271-276
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate the associations between markers of systemic and vascular inflammation, and indicators of vascular morphology and function. METHODS: In 59 apparently healthy individuals, we measured serum levels of highly sensitive C-reactive protein (hsCRP), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin. Endothelium-dependent (EDV) and -independent (EIDV) vasodilatation was evaluated in the forearm by venous occlusion plethysmography and local infusions of methacholine and sodium nitroprussid. Endothelial function index (EFI) was expressed as the EDV/EIDV ratio. The intima-media thickness (IMT) of the common carotid artery was investigated with ultrasound (far wall). RESULTS: EFI was inversely related only to ICAM-1 (r=-0.31, P<0.02) by univariate analysis. This association remained significant after adjustment for age, sex, blood pressure, smoking and serum cholesterol. EFI did not relate to hsCRP, VCAM-1 or E-selectin. Neither hsCRP, nor the adhesion molecules were significantly related to carotid artery IMT. CONCLUSION: ICAM-1 was related to endothelial vasodilatory function, but not to IMT, suggesting that endothelial inflammatory activation is related to an impaired vascular relaxation in apparently healthy individuals.
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| 9. |
- Krettek, Alexandra, 1968-, et al.
(författare)
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Expression of PDGF receptors and ligand-induced migration of partially differentiated human monocyte-derived macrophages. Influence of IFN-gamma and TGF-beta
- 2001
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Ingår i: Atherosclerosis. - : Elsevier. - 0021-9150 .- 1879-1484. ; 156:2, s. 267-275
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Tidskriftsartikel (refereegranskat)abstract
- In the early atherosclerotic lesion, monocytes accumulate at sites of inflammation and endothelial injury. Platelet-derived growth factor (PDGF), produced for example by macrophages, is a chemoattractant for smooth muscle cells and possibly also for macrophages. During early differentiation into macrophages, human monocytes (early hMDM) showed lower expression of PDGF alpha-receptor (PDGF-Ralpha) than beta-receptor (PDGF-Rbeta) mRNA. Early hMDM showed increased random motility (chemokinesis) in the presence of PDGF of the long (BB(L)) but not short (BB(S)) B-chain homodimer. Neither PDGF-AA(S) nor PDGF-AA(L) affected early hMDM motility. Since increased cytokine levels accompany inflammation, the influence of interferon-gamma (IFN-gamma) and transforming growth factor-beta (TGF-beta) on PDGF-R expression and migratory response were studied. Only PDGF-Ralpha mRNA was highly upregulated by IFN-gamma. TGF-beta only had minor effects on receptor mRNAs. Upregulation of PDGF-Ralpha levels by IFN-gamma was accompanied by significantly increased migration (chemotaxis) towards PDGF-AA(L) only. Consequently, IFN-gamma modulates PDGF-Rs expression in early hMDM and, subsequently, the chemotactic activity of PDGF-AA(L) on IFN-gamma-stimulated early hMDM. This suggests that PDGF-AA(L) may be involved in attracting activated monocytes to sites of inflammation and injury.
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| 10. |
- Kristenson, Margareta, 1950-, et al.
(författare)
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Ultrasound determined carotid and femoral atherosclerosis in Lithuanian and Swedish men : The LiVicordia study
- 2000
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Ingår i: Atherosclerosis. - 0021-9150 .- 1879-1484. ; 151:2, s. 501-508
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Tidskriftsartikel (refereegranskat)abstract
- Coronary heart disease mortality is four times higher in Lithuanian compared to Swedish middle-aged men. Using the same equipment (Acuson XP10 with 5 MHz linear transducer) and staff, we compared the amount of atherosclerosis in carotid and femoral arteries in 100 randomly sampled 50-year-old men in each of the cities Vilnius, Lithuania and Linköping, Sweden. Atherosclerotic plaques were more abundant in Vilnius men compared to Linköping men (53 versus 28% in the common carotid artery, 73 versus 37% in the common femoral artery, P<0.001 for both). Plaques were thicker and more extended in arteries of Vilnius men, and an ultrasound atherosclerosis score was higher in both carotid and femoral arteries (P<0.001 for all). More Vilnius men had a maximal intima-media thickness of the common femoral artery above 1 mm (P<0.005). Stiffness in the common carotid artery was higher in Vilnius men (P<0.001). In a linear regression model of the pooled material, after adjustment for city was made, smoking, systolic blood pressure, low density lipoprotein cholesterol and β-carotene (inversely) significantly contributed to a high total ultrasound score (r2=0.32). These findings show that the higher coronary mortality noted in Lithuanian men goes together with a higher prevalence of early peripheral atherosclerosis.
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