Also see:
Unsaturated Fats and Heart Damage
PUFA, Fish Oil, and Alzheimers
Thyroid Status and Cardiovascular Disease
“Normal” TSH: Marker for Increased Risk of Fatal Coronary Heart Disease
A Cure for Heart Disease
Hypothyroidism and A Shift in Death Patterns
Thyroid Status and Oxidized LDL
Unsaturated Fats and Longevity
PUFA Accumulation & Aging
Arterioscler Thromb Vasc Biol. 1997 Nov;17(11):3236-41.
Prostaglandin F2-like compounds, F2-isoprostanes, are present in increased amounts in human atherosclerotic lesions.
Gniwotta C, Morrow JD, Roberts LJ 2nd, Kühn H.
Oxidative modification of LDL is believed to play a major role in atherogenesis. As major lipid peroxidation products oxygenated linoleic acid derivatives and oxysterols have been described in human atherosclerotic lesions. Here we report that human lesions contain isoprostanes as peroxidation products of arachidonic acid at a level of 27.1 +/- 21.2 pg/mg wet weight (n = 10), which corresponds to 75.9 +/- 59.3 pg/mg dry weight, n contrast, human umbilical veins (n = 10), which were used as nonatherosclerotic control vessels, contain much smaller amounts of isoprostanes (1.4 +/- 0.7 pg/mg wet weight, which corresponds to 11.7 +/- 6.2 pg/mg dry weight), and there are significant differences between the two types of vessels. As major products of linoleic acid oxidation, racemic hydroxy linoleate isomers were detected in the lesional ester lipids. In human lesions, the hydroxy linoleic acid/linoleic acid ratio was about 0.5%, a result indicating that 5 out of 1000 linoleate residues are present as hydroxylated derivatives. In umbilical veins, no hydroxy linoleic acid could be detected. These data show that human atherosclerotic lesions contain increased amounts of hydroxy linoleic acid isomers and isoprostanes when compared with nonatherosclerotic vessel wall and suggest a link between local lipid peroxidation and progression of atherosclerosis. For evaluation of the degree of lipid peroxidation, the determination of the hydroxy linoleic acid/linoleic acid ratio appears to be more suitable than the isoprostane content.
Atherosclerosis. 2003 Mar;167(1):111-20.
Fatty acid oxidation products in human atherosclerotic plaque: an analysis of clinical and histopathological correlates.
Waddington EI, Croft KD, Sienuarine K, Latham B, Puddey IB.
Markers of lipid peroxidative damage have been shown to be elevated in individuals with risk factors for cardiovascular disease, and human atherosclerotic plaque contains products resulting from lipid peroxidation. In particular, the presence of fatty acid oxidation products such as hydroxyeicosatetraenoic acids (HETEs) has previously been suggested as a marker of plaque instability and symptomatic cerebrovascular disease. The aim of the present study was to quantitate the levels of various oxidation products of linoleic acid (HODEs) and arachidonic acid (HETEs), respectively, in human atherosclerotic plaque tissue and assess their level in relation to plaque histopathology, symptoms of cerebrovascular disease and preexisting atherosclerotic risk factors. We also assessed the correlation between the levels of the hydroxy fatty acid compounds and F(2)-isoprostanes, an established marker of in vivo free radical mediated oxidation. Hydroxy fatty acid oxidation products were identified in all histological subtypes of advanced plaque. However, there were no significant differences in levels between the histopathologically classified sub-groups or between patients symptomatic or asymptomatic for cerebrovascular disease. Arachidonic acid oxidation products were significantly higher in those subjects who also had symptomatic peripheral vascular disease. The level of linoleic acid oxidation products was significantly higher in individuals who consumed alcohol on a regular basis. While F(2)-isoprostanes and fatty acid oxidation products were highly correlated (P<0.01), levels of the hydroxy fatty acid compounds were 20-40-fold higher than F(2)-isoprostanes. Chiral analysis of the plaque extracts indicated that all HODEs and HETEs originated primarily from non-enzymatic lipid peroxidation. While our results do not support previous reports that fatty acid oxidation products such as the HETEs are associated with plaque instability and symptomatic cerebrovascular disease, further work is warranted to determine the potential of these compounds as circulating markers for underlying atherosclerotic disease and lipid peroxidative stress.
Anal Biochem. 2001 May 15;292(2):234-44.
Identification and quantitation of unique fatty acid oxidation products in human atherosclerotic plaque using high-performance liquid chromatography.
Waddington E, Sienuarine K, Puddey I, Croft K.
Oxidation of lipoproteins, particularly low-density lipoprotein, is thought to play a major role in the development of atherosclerosis. We set out to identify and quantitate the major fatty acid oxidation products in human atherosclerotic plaque obtained from individuals undergoing carotid endarterectomy. Oxidized lipids were extracted from plaque homogenate under conditions to prevent artifactual oxidation. Identification and quantitation was performed using HPLC and GC-MS. High levels of hydroxyoctadecanoic acids (0.51 +/- 0.17 ng/microg of linoleic acid), 15-hydroxyeicosatetranoic acid (HETE) (0.66 +/- 0.24 ng/microg of arachidonic acid), and 11-HETE (0.84 +/- 0.24 ng/microg of arachidonic acid) were detected in all atherosclerotic plaques (n = 10). Low levels of 9-oxo-octadecanoic acid (oxoODE) (0.04 +/- 0.01 ng/microg of linoleic acid), were present in all samples, while 13-oxoODE (0.01 +/- 0.008 ng/microg of linoleic acid) was present in only 4 of the 10 plaque samples. Of interest was the identification of two previously unidentified compounds in atherosclerotic plaque, 11-oxo-eicosatetranoic acid in 9 of the 10 samples and 5,6-dihydroxyeicosatetranoic acid in 3 samples. Chiral analysis revealed that all the major compounds identified in this study are of a nonenzymatic origin. This study is the first to provide a convenient HPLC method to quantify all the products of both linoleic acid and arachidonic acid oxidation in human atherosclerotic plaque. The quantitation of lipid peroxidation products in plaque may be important given the potential biological activity of these compounds and their possible relationship to plaque pathogenesis and instability.
Free Radic Biol Med. 2006 Dec 1;41(11):1678-83. Epub 2006 Sep 8.
Systemic elevations of free radical oxidation products of arachidonic acid are associated with angiographic evidence of coronary artery disease.
Shishehbor MH, Zhang R, Medina H, Brennan ML, Brennan DM, Ellis SG, Topol EJ, Hazen SL.
Oxidant stress is widely believed to participate in cardiovascular disease pathogenesis. However, progress in defining appropriate systemic antioxidant targeted therapies has been hindered by uncertainty in defining clinically relevant systemic oxidant stress measures. In a case control study, 50 subjects with CAD (>50% stenosis in one or more major coronary vessels) and 54 without CAD (<30% stenosis in all major coronary vessels) were tested. Plasma was isolated and stored under conditions designed to prevent artificial lipid peroxidation. Systemic levels of multiple (n=9) specific fatty acid oxidation products including individual hydroxyoctadecadienoic acids (HODEs), hydroxyeicosatetraenoic acids (HETEs), and F(2)-isoprostanes were simultaneously measured by high-performance liquid chromatography (HPLC) with on-line tandem mass spectrometry, along with traditional risk factors and C-reactive protein (CRP) levels. Of the markers monitored, only 9-HETE and F(2)-isoprostanes, both products of free radical-mediated arachidonic acid oxidation, were significantly elevated in patients with angiographically defined CAD (9-HETE, 8.7 +/- 4 vs 6.8 +/- 4 micromol/mol arachidonate, P = 0.011; and F(2)-isoprostanes, 9.4 +/- 5 vs 6.2 +/- 3 micromol/mol arachidonate, P < 0.001). In multivariable analyses with simultaneous adjustment for Framingham risk score and C-reactive protein, 9-HETE (4th quartile OR = 4.8, 95% CI=1.3 to 17.1; P = 0.016) and F(2)-isoprostanes (4th quartile OR=9.7, 95% CI=2.56 to 36.9; P < 0.001) remained strong and independent predictors of CAD risk. Systemic levels of 9-HETE and F(2)-isoprostanes are independently associated with angiographic evidence of CAD and appear superior to other specific oxidation products of arachidonic and linoleic acids as predictors of the presence of angiographically evident coronary artery disease.
Lancet. 1994 Oct 29;344(8931):1195-6.
Dietary polyunsaturated fatty acids and composition of human aortic plaques.
Felton CV, Crook D, Davies MJ, Oliver MF.
How long-term dietary intake of essential fatty acids affects the fatty-acid content of aortic plaques is not clear. We compared the fatty-acid composition of aortic plaques with that of post-mortem serum and adipose tissue, in which essential fatty-acid content reflects dietary intake. Positive associations were found between serum and plaque omega 6 (r = 0.75) and omega 3 (r = 0.93) polyunsaturated fatty acids, and monounsaturates (r = 0.70), and also between adipose tissue and plaque omega 6 polyunsaturated fatty acids (r = 0.89). No associations were found with saturated fatty acids. These findings imply a direct influence of dietary polyunsaturated fatty acids on aortic plaque formation and suggest that current trends favouring increased intake of polyunsaturated fatty acids should be reconsidered.
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Established role of isoprostanes, formed from arachidonic acid, in disease and marker for oxidative stress.
Rev Med Interne. 2000 Mar;21(3):304-7.
[Isoprostanes: new markers of oxidative stress. Fundamental and clinical aspects].
[Article in French]
Cracowski JL, Stanke-Labesque F, Bessard G.
A novel family of prostaglandin F2 isomers, called F2-isoprostanes, produced in large quantities in vivo by a free radical peroxidation of arachidonic acid, has recently been described. The quantification of the two major isoforms (isoprostaglandin F2alpha type-III and VI) in biological fluids and tissues as markers of lipid peroxidation appears to be an important advance in our ability to explore the role of free radicals in the pathogenesis of human disease. In addition, F2-isoporstanes quantification seems promising as intermediate endpoints for clinical studies of antioxidant therapies.
Presse Med. 2000 Mar 25;29(11):604-10.
[Isoprostanes: new markers of oxidative stress in human diseases].
[Article in French]
Cracowski JL, Stanke-Labesque F, Souvignet C, Bessard G.
BACKGROUND:
Most of the traditional methods used to assess oxidative stress in clinical setting are non specific, unreliable or inaccurate. Recently, a novel family of prostaglandin F2 isomers, called F2-isoprostanes, produced in vivo by a free radical peroxidation of arachidonic acid, has been described. These compounds may produce physiological or pathological effects due to their ability to alter smooth muscle and platelet functions. The quantification of the two major isoforms (isoprostaglandin F2 alpha type-III and VI) in biological fluids and tissues as markers of lipid peroxidation appears to be an important advance in our ability to explore the role of free radicals in the pathogenesis of human disease.
CLINICAL DATA:
Urinary excretion of F2-isoprostanes is correlated with age, indicating increased oxidative stress during the normal aging process. High F2-isoprostanes concentration has been described in diseases such as ischemic heart disease, diabetes, Alzheimer’s disease and hepatic cirrhosis. The correlation of F2-isoprostane concentrations and human diseases severity in hepatic cirrhosis, cardiac failure and diabetes suggest that these compounds may be of interest as predictive markers.
PERSPECTIVES:
Preliminary studies suggest the use of F2-isoprostanes as prognosis markers. In addition, F2-isoprostanes quantification offers promising potential as intermediate endpoints for clinical studies of antioxidant therapies.
