<p>Inflammation and oxidative stress may be involved in atherogenesis. This thesis describes clinical studies of prostaglandin F<sub>2α</sub> (PGF<sub>2α</sub>), an inflammatory mediator, and the isoprostane 8-iso-PGF<sub>2α</sub>, a reliable indicator of oxidative stress, and cytokine-related inflammatory mediators and indicators in healthy subjects and in a population-based cohort of Swedish men. </p><p>PGF<sub>2α</sub> and 8-iso-PGF<sub>2α</sub> formation in healthy subjects varied considerably between days with a mean intra-individual coefficient of variation of 41 % and 42 %, respectively. A morning urine sample reflected the basal level of 8-iso-PGF<sub>2α</sub> formation as accurately as a 24-hour urine collection, and represents a more practical alternative to the 24-hour urine collection in clinical studies. PGF<sub>2α</sub> formation (as measured by urinary 15-keto-dihydro-PGF<sub>2α</sub>) was increased in patients with type 2 diabetes and in smokers independent of other cardiovascular risk factors. These results indicated an on-going cyclooxygenase (COX)-mediated inflammatory reaction related to these conditions. Further, an increased formation of isoprostanes (as measured by urinary 8-iso-PGF<sub>2α</sub>) was found in patients with type 2 diabetes and in smokers, indicating a high level of oxidative stress in these men. The smokers had also increased levels of the cytokine interleukin-6, indicating an on-going cytokine-related inflammatory reaction. The inflammatory indicators C-reactive protein and serum amyloid A were related to overweight but not independently associated to type 2 diabetes. High levels of serum selenium in middle-aged men predicted reduced formation of PGF<sub>2α</sub> and 8-iso-PGF<sub>2α</sub> 27 years later.</p><p>In summary, low-grade, chronic COX-mediated and possibly cytokine-related inflammation, and oxidative stress, seem to be joint features of type 2 diabetes and smoking, two major risk factors of atherosclerosis, in elderly men. Inflammation and oxidative stress may represent a possible common pathogenetic link between established risk factors for atherosclerosis and atherogenesis.</p>
| Identifer | oai:union.ndltd.org:UPSALLA/oai:DiVA.org:uu-4803 |
| Date | January 2005 |
| Creators | Helmersson, Johanna |
| Publisher | Uppsala University, Clinical Nutrition Research, Uppsala : Acta Universitatis Upsaliensis |
| Source Sets | DiVA Archive at Upsalla University |
| Language | English |
| Detected Language | English |
| Type | Doctoral thesis, comprehensive summary, text |
| Relation | Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, 1651-6206 ; 9 |
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