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- Hulthe, Johannes, 1970, et al.
(författare)
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Plasma interleukin (IL)-18 concentrations is elevated in patients with previous myocardial infarction and related to severity of coronary atherosclerosis independently of C-reactive protein and IL-6
- 2006
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Ingår i: Atherosclerosis. - : Elsevier BV. - 0021-9150. ; 188:2, s. 450-4
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Tidskriftsartikel (refereegranskat)abstract
- AIM: Interleukin-18 (IL-18) is a pro-inflammatory cytokine with a central role in the inflammatory cascade. In the present study, we investigated whether patients with precocious myocardial infarction have higher plasma IL-18 concentrations than matched controls. Furthermore, the relationships between plasma IL-18 concentrations and coronary atherosclerosis, C-reactive protein (CRP), interleukin-6 (IL-6) and traditional cardiovascular risk factors were examined. METHODS AND RESULTS: Three hundred eighty-seven unselected survivors of a first myocardial infarction aged less than 60 years and 387 sex and age matched controls were enrolled in the study. A subset of patients (n=236) was evaluated by quantitative coronary angiography. Postinfarction patients had significantly higher mean level of plasma IL-18 than controls (309.6+/-138.6 versus 285.4+/-115.7pg IL-18/mL). Furthermore, plasma IL-18 concentration was significantly associated with coronary plaque area (r=0.17, p=0.009). This relationship remained in a partial correlation analysis adjusting for CRP (r=0.15, p=0.02), for IL-6 (r=0.15, p=0.02) and for both CRP and IL-6 (r=0.15, p=0.02). In addition, IL-18 levels were significantly associated with other cardiovascular risk factors, namely age, low density lipoprotein (LDL) cholesterol, triglycerides, high density lipoprotein (HDL) cholesterol, insulin, proinsulin, body mass index (BMI), systolic and diastolic blood pressure. CONCLUSION: The present work provides evidence that plasma IL-18 is increased in postinfarction patients and is associated with coronary atherosclerosis.
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| 2. |
- Knutsen Rydberg, Ellen, 1969, et al.
(författare)
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Hypoxia increases LDL oxidation and expression of 15-lipoxygenase-2 in human macrophages
- 2004
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Ingår i: Arterioscler Thromb Vasc Biol. ; 24:11, s. 2040-2045
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Macrophage-mediated oxidation of low-density lipoprotein (LDL) by enzymes, such as the lipoxygenases, is considered of major importance for the formation of oxidized LDL during atherogenesis. Macrophages have been identified in hypoxic areas in atherosclerotic plaques. METHODS AND RESULTS: To investigate the role of hypoxia in macrophage-mediated LDL oxidation, we incubated human monocyte-derived macrophages with LDL under normoxic (21% O2) or hypoxic (0% O2) conditions. The results showed that hypoxic macrophages oxidized LDL to a significantly higher extent than normoxic cells. Interestingly, the mRNA and protein expression of 15-lipoxygenase-2 (15-LOX-2) as well as the activity of this enzyme are elevated in macrophages incubated at hypoxia. Both the unspliced 15-LOX-2 and the spliced variant 15-LOX-2sv-a are found in macrophages. In addition, 15-LOX-2 was identified in carotid plaques in some macrophage-rich areas but was only expressed at low levels in nondiseased arteries. CONCLUSIONS: In summary, these observations show for the first time that 15-LOX-2 is expressed in hypoxic macrophages and in atherosclerotic plaques and suggest that 15-LOX-2 may be one of the factors involved in macrophage-mediated LDL oxidation at hypoxia.
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