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ST-segment elevation myocardial infarction (STEMI) occurs as a result of acute occlusion of the coronary artery. Despite successful reperfusion using primary percutaneous coronary intervention (PPCI), a large percentage of myocardial cells die after reperfusion, which is recognized as ischemia/reperfusion injury (I/R). There are rapid changes in plasma lipidome during myocardial reperfusion injury. However, the impact of coronary artery reperfusion on plasma oxylipins is unknown. This study aimed to investigate alterations in the oxylipin profiles of STEMI patients during ischemia and at various reperfusion time points following PPCI. Blood samples were collected from patients presenting with STEMI prior to PPCI (Isch, n = 45) and subsequently 2 h following successful reperfusion by PPCI (R-2 h, n = 42), after 24 h (R-24 h, n = 44), after 48 h (R-48 h, n = 43), and then 30 days post PPCI (R-30 d, n = 29). As controls, blood samples were collected from age- and sex-matched patients with non-obstructive coronary artery disease after diagnostic coronary angiography. High-performance liquid chromatography–mass spectrometry (HPLC-MS/MS) using deuterated standards was used to identify and quantify oxylipins. In patients presenting with STEMI prior to reperfusion (Isch group), the levels of docosahexaenoic acid (DHA)-derived oxylipins were significantly higher when compared with controls. Their levels were also significantly correlated with the peak levels of creatine kinase (CK) and troponin T(TnT) before reperfusion (CK: r = 0.33, p = 0.046, TnT: r = 0.50, p = 1.00 × 10−3). The total concentrations of oxylipins directly produced by 5-lipoxygenase (5-LOX) were also significantly elevated in the Isch group compared with controls. The ratio of epoxides (generated through epoxygenase) to diols (generated by soluble epoxide hydrolysis (sEH)) was significantly lower in the Isch group compared with the controls. Following reperfusion, there was an overall reduction in plasma oxylipins in STEMI patients starting at 24 h post PPCI until 30 days. Univariate receiver operating characteristic (ROC) curve analysis also showed that an elevated ratio of epoxides to diols during ischemia is a predictor of smaller infarct size in patients with STEMI. This study revealed a large alteration in plasma oxylipins in patients presenting with STEMI when compared with controls. Total oxylipin levels rapidly reduced post reperfusion with stable levels reached 24 h post reperfusion and maintained for up to 30 days post infarct. Given the shifts in plasma oxylipins following coronary artery reperfusion, further research is needed to delineate their clinical impact in STEMI patients. [ABSTRACT FROM AUTHOR]

Oxylipins and fatty acids may be novel therapeutic targets for cardiovascular disease. The objective was to determine if plasma oxylipins or fatty acids can influence the odds of cardiovascular/cerebrovascular events. In 98 patients (25 female, 73 male) with peripheral artery disease, the prevalence of transient ischemic attacks, cerebrovascular accidents, stable angina, and acute coronary syndrome was n = 16,10,16, and 24, respectively. Risk factors such as being male, diagnosed hypertension, diabetes mellitus, and hyperlipidemia were not associated with events. Plasma fatty acids and oxylipins were analyzed with gas chromatography and HPLC-MS/MS, respectively. None of 24 fatty acids quantified were associated with events. In contrast, 39 plasma oxylipins were quantified, and 8 were significantly associated with events. These 8 oxylipins are known regulators of vascular tone. For example, every 1 unit increase in Thromboxane [B.sub.2]/Prostaglandin [F.sub.1[alpha]] and every 1 nmol/L increase in plasma 16-hydroxyeicosatetraenoic acid, thromboxane B2, or 11,12-dihydroxyeicosatrienoic acid (DiHETrE) increased the odds of having had [greater than or equal to] 2 events versus no event (p < 0.05). The greatest predictor was plasma 8,9-DiHETrE, which increased the odds of acute coronary syndrome by 92-fold. In conclusion, specific oxylipins were highly associated with clinical events and may represent specific biomarkers and (or) therapeutic targets of cardiovascular disease. Key words: lipidomics, myocardial infarction, cerebrovascular accident, oxylipin, fatty acid. Les oxylipines et les acides gras pourraient constituer de nouvelles cibles therapeutiques pour les maladies cardiovasculaires. Notre objectif etait d'etablir si les oxylipines ou les acides gras plasmatiques peuvent influencer les probabilites d'observer des evenements cardiovasculaires ou vasculaires cerebraux. Chez 98 patients (25 femmes, 73 hommes) atteints de maladie arterielle peripherique, les cas d'ischemie cerebrale transitoire, d'accidents vasculaires cerebraux, d'angine stable et de syndrome coronarien aigu etaient au nombre de 16, de 10, de 16 et de 24, respectivement. Les facteurs de risque comme le sexe masculin ainsi que les diagnostics d'hypertension, de diabete sucre et d'hyperlipidemie n'etaient pas associes a des evenements indesirables. Nous avons analyse les acides gras et les oxylipines dans le plasma a l'aide de la chromatographie gazeuse et de la chromatographie liquide de haute performance avec spectrometrie de masse ou la spectrometrie de masse seule, respectivement. Aucun des 24 acides gras quantifies n'a ete associe a des evenements indesirables. Inversement, nous avons quantifie 39 oxylipines plasmatiques, dont 8 etaient associees de facon robuste a des evenements indesirables. Ces 8 oxylipines sont des regulateurs connus du tonus vasculaire. Par exemple, chaque augmentation d'une unite de thromboxane [B.sub.2]/prostaglandine [F.sub.1[alpha]] et chaque augmentation des taux d'acide 16-hydroxyeicosatetraenolque, de thromboxane B2 ou d'acide 11, 12-dihydroxyeicosatrienoique (DiHETrE) dans le plasma de l'ordre de 1 nmol/L entrainait une augmentation de la probabilite de presenter au moins 2 evenements indesirables par rapport a celle de ne presenter aucun evenement indesirable (p < 0,05). Le facteur de prediction le plus important etait le taux de 8,9-DiHETrE, qui entrainait une augmentation de la probabilite de presenter un syndrome coronarien aigu de l'ordre de 92 fois. En conclusion, des oxylipines specifiques etaient fortement associees a des evenements indesirables cliniques et pourraient representer des biomarqueurs specifiques et/ou des cibles therapeutiques pour les maladies cardiovasculaires. [Traduit par la Redaction] Mots-cles: lipidomique, infarctus du myocarde, accident vasculaire cerebral, oxylipine, acide gras., Introduction Oxylipins are an intriguing group of molecules due to their ability to regulate inflammation and vascular tone (Gabbs et al. 2015; Nishimaki and Seki 1999; Norris and Dennis 2014; [...]

Despite evidence of potential antiobesity effects of high-protein (HP) diets, the impact of consuming diets with protein levels at the upper limit of the acceptable macronutrient distribution range (AMDR) on kidney health is unknown. To test whether HP diets affect renal health, whole plant and animal proteins in proportions that mimicked human diets were given to pigs, because their kidneys have a similar anatomy and function to those of humans. Adult female pigs received either normal-protein (NP) or HP (15 or 35% of energy from protein, respectively) isocaloric diets for either 4 or 8 mo. The higher protein in the HP diet was achieved by increasing egg and dairy proteins. Although there were initial differences in body weight and composition, after 8 mo these were similar in pigs consuming the NP and HP diets. The HP compared with NP diet, however, resulted in enlarged kidneys at both 4 and 8 mo. Renal and glomerular volumes were 60-70% higher by the end of the study. These enlarged kidneys had greater evidence of histological damage, with 55% more fibrosis and 30% more glomerulosclerosis. Renal monocyte chemoattractant protein-1 levels also were 22% higher in pigs given the HP diet. Plasma homocysteine levels were higher in the HP pigs at 4 mo and continued to be elevated by 35% at 8 mo of feeding. These findings suggest that long-term intakes of protein at the upper limit of the AMDR from whole protein sources may compromise renal health. J. Nutr. 140: 1646-1652, 2010. doi: 10.3945/jn.110.123034.

Long-term consumption of high-protein (HP) diets at 35% of energy is postulated to negatively influence bone health. Previous studies have not comprehensively examined the biochemical, physical, and biomechanical properties of bone required to arrive at this conclusion. Our objective in this study was to examine the Iong-term effect of a HP diet on bone metabolism, mass, and strength in rats. Adult female Sprague-Dawley rats (n = 80) were randomized to receive for 4, 8, 12, or 17 mo a normal-protein (NP) control diet (15% of energy) ora HP diet (35% of energy). Diets were balanced for calcium because the protein sources were rich in calcium. At each time point, measurements included weight, body composition, and bone mass using dual-energy X-ray absorptiometry, mechanical strength at the mid-diaphysis of femur and tibia, microarchitecture of femurs using microcomputerized tomography and serum osteocalcin, carboxy-terminal crosslinks of type I collagen (CTX), insulin-like growth factor-1 (IGF-1), leptin, and adiponectin. Effects of diet, time, and their interaction were tested using factorial ANOVA. The HP diet resulted in Iower body weight, total body, and abdominal fat and higher lean mass. Serum leptin and adiponectin were greater in HP-fed than in NP-fed rats, but IGF-1 did not differ between the groups. Whereas the HP diet resulted in higher relative bone mineral content (g/kg)in the femur, tibia, and vertebrae, serum osteocalcin and CTX and bone internal architecture and biomechanical strength were unaffected. In conclusion, HP diets at 35% of energy Iower body fat content without hindering the mechanical and weight-bearing properties of bone. J. Nutr. 139: 2099-2105, 2009. doi: 10.3945/jn.109.106377

We recently demonstrated that (n-3) PUFA trigger the induction of apoptosis in the colon by enhancing phospholipid oxidation and mitochondrial [Ca.sup.2+] accumulation. To further elucidate the mechanisms regulating oxidative stress-induced apoptosis in vivo, a 2 x 2 experiment was designed using both wild type (control) and manganese-dependent superoxide dismutase (SOD2) heterozygous knockout mice ([SOD2.sup.+/-]), which exhibit increased mitochondrial oxidative stress. Mice were fed diets differing only in the type of fat [corn oil or fish oil containing (n-3) PUFA] at 15% by weight for 4 wk. Dietary (n-3) PUFA treatment enhanced (22%) apoptosis in colonic crypts. In addition, SOD2 haploinsufficiency enhanced (20%) apoptosis, which was further increased (36%) by (n-3) PUFA feeding. Dietary lipid source and genotype interactively modulated nitrotyrosine levels (P = 0.027) and inflammation (P = 0.032). These findings demonstrate that the proapoptotic effects of (n-3) PUFA are enhanced in oxidatively stressed [SOD2.sup.+/-] mice. Thus, (n-3) PUFA appear to promote an oxidation-reduction imbalance in the intestine, which may directly or indirectly trigger apoptosis and thereby reduce colon cancer risk.

Conjugated linoleic acid (CLA) slows the progression of disease in models of chronic kidney disease. Because obesity is associated with nephropathy and increased renal cyclooxygenase (COX) levels, the effects of dietary CLA on kidney function, morphology, and COX protein levels in the kidneys of young obese (fa/fa) Zucker rats, a model of metabolic syndrome, were examined. In study 1,6-wk-old fa/fa and lean Zucker rats were given a mixture of CLA isomers (1.5% CLA, wt:wt) or the control diet (CTL) with no CLA for 8 wk. To examine specific isomer effects, study 2 used the same model with the following diets: 0.4% (g/g) cis-9, trans-11 (c9,t11) CLA; 0.4% trans-10, cis-12 (t10,c12) CLA; a combination of these 2 isomers (0.4% each); or CTL diets with no CLA. In study 1, fa/fa rats given the CLA mixture had 11% smaller kidney weights and 28% smaller glomeruli, and feed intake and body weight did not differ from the CTL rats. In study 2, diet also did not affect body weights, but fa/fa rats given a diet containing t10, c12 CLA had 7% lower kidney weights, 20% smaller glomeruli, and 39% lower COX-2 protein levels than CTL rats. In conclusion, dietary t10,c12 CLA reduces the enlargement of glomeruli in young obesity-associated nephropathy and is associated with lower protein levels of renal COX-2. Long-term studies with CLA supplementation are required to determine whether these changes would lead to reduction in development of renal disease associated with obesity.