Delta-6-desaturase gene polymorphism is associated with lipoprotein oxidation in vitro.

BACKGROUND: Oxidative modification of low-density lipoprotein (LDL) is a key event in the oxidation hypothesis of atherogenesis. We have previously shown that HDL does not protect LDL from oxidation in vitro, but is in fact oxidized fastest of all lipoproteins due to its rich polyunsaturated fatty acid (PUFA) composition, which is oxidation promoting. Evidence has accumulated to show that in addition to diet, common polymorphisms in the fatty acid desaturase (FADS) gene cluster have very marked effects on human PUFA status. There is a deletion [T/-] in the promoter region of the Δ6 -desaturase gene (FADS2, rs 3834458), which has a direct inhibitory influence on production of PUFA from linoleic and alpha-linolenic acid. To investigate the possible role of rs 3834458 in lipoprotein modification, oxidation of LDL with HDL2 or HDL3 were analyzed from plasma of 58 free-living individuals. RESULTS: Total eicosapentaenoic acid and arachidonic acid were significantly decreased in plasma from the 10 subjects homozygous for the deletion in FADS2 rs 3834458. When the isolated LDL and HDL2 were subjected to Cu²âº-induced oxidation, these subjects showed decreased rate of appearance (p = 0.027) and the final concentration of conjugated dienes (p = 0.033) compared to the other genotypes. For oxidation of LDL with HDL3, the final concentration of conjugated dienes was also significantly decreased in subjects with [-/-] compared with [T/T] and [T/-] (p = 0.034). CONCLUSION: We conclude that FADS2 genotype may play a role in peroxidation susceptibility of lipoproteins.

Bacterial DNA signatures in carotid atherosclerosis represent both commensals and pathogens of skin origin.

Infectious agents have been suggested to be involved in atherosclerosis. By using a novel subtraction broad-range PCR approach, we defined bacterial DNA signatures in surgically removed sterile carotid artery endarterectomy plaques of patients with carotid atherosclerosis. Eighty partial bacterial 16S rDNA nucleotide sequences from eight patients were studied. Furthermore, 34 clones representing 21 bacterial sequence-types from the reagents used for DNA extraction and PCR amplification were determined. After subtraction of these potential methodological contaminants, 23 bacterial sequence-types were considered as clinically relevant findings. The most prominent phylum, Actinobacteria, accounted for 74% of these relevant sequences. Furthermore, according to the Human Microbiome project database, interestingly, nearly all (94%) of the sequences were associated with the human skin microbiome.

Late-life coronary heart disease mortality of Finnish war veterans in the TAMRISK study, a 28-year follow-up.

BACKGROUND: Wartime stress has been associated with increased late-life mortality of all causes of death. We evaluated whether wounded Finnish World War II veterans who were alive at the age of 55 have increased long-term coronary heart disease (CHD) mortality. METHODS: Health survey data were recorded in 1980 from 667 men, aged 55 years. Of them 102 had been wounded or injured in action during 1939-1945. The remaining participants served as the comparison group. The death certificates during a 28-year follow-up were obtained from the national statistics centre. Statistical comparisons were done by Cox proportional hazard regression model. RESULTS: There were altogether 140 deaths from CHD. In men who had been wounded or injured in action the crude CHD mortality rate per 10,000 population was 2843, while in the comparison group the corresponding figure was 1961. Men who had been wounded or injured in action were 1.7 times (95% CI 1.1-2.5; p = 0.01) more likely to die from CHD than the comparison group. CONCLUSIONS: Physical trauma at young adulthood may extend to lifelong effects on health. This study suggests that being physically wounded or injured in war may lead to increased CHD mortality in late adulthood in a Finnish population.

Bacterial signatures in atherosclerotic lesions represent human commensals and pathogens.

BACKGROUND: Various studies have suggested the involvement of infectious agents in chronic inflammatory diseases, including atherosclerosis. By using a novel subtraction broad-range PCR approach, we defined bacterial DNA signatures in surgically removed sterile abdominal aorta samples of patients with aortic atherosclerosis. METHODS: Partial bacterial 16S rDNA nucleotide sequences were determined using broad-range PCR from aortic samples of 20 patients, and from appropriate methodological controls. In all, 160 sequences from 16 clone libraries were studied. RESULTS: After subtraction analysis 16 clinically relevant bacterial sequence-types were identified among the patient samples, whereas 29 were discarded as potential methodological contaminants. On average 2.2+/-1.2 different bacterial sequence-types were present in the nine true PCR-positive atheroma samples. CONCLUSIONS: Many studies have reported the presence of a variety of bacterial sequences from atherosclerotic lesions. However, the results obtained with these PCR technologies may have been skewed by methodological contaminants. After our subtraction approach, 63% of the remaining sequence-types from sites of aortic atherosclerosis were related to those of known human pathogens. This may imply that advanced atherosclerotic plaques accumulate bacterial DNA.