Peripheral Artery Disease Is Associated with a Deficiency of Erythrocyte Membrane n-3 Polyunsaturated Fatty Acids

Population-based data suggest that individuals who consume large dietary amounts of n-3 polyunsaturated fatty acids (PUFA) have lower odds of peripheral artery disease (PAD); however, clinical studies examining n-3 PUFA levels in patients with PAD are sparse. The objective of this study is to compare erythrocyte membrane fatty acid (FA) content between patients with PAD and controls. We conducted a cross-sectional study of 179 vascular surgery outpatients (controls, 34; PAD, 145). A blood sample was drawn and the erythrocyte FA content was assayed using capillary gas chromatography. We calculated the ratio of the n-3 PUFA eicosapentaenoic acid (EPA) to the n-6 PUFA arachidonic acid (ARA) as well as the omega-3 index (O3I), a measure of erythrocyte content of the n-3 PUFA, EPA, and docosahexaenoic acid (DHA), expressed as a percentage of total erythrocyte FA. Compared with controls, patients with PAD smoked more and were more likely to have hypertension and hyperlipidemia (p < 0.05). Patients with PAD had a lower mean O3I (5.0 ± 1.7% vs 6.0 ± 1.6%, p < 0.001) and EPA:ARA ratio (0.04 ± 0.02 vs 0.05 ± 0.05, p < 0.001), but greater mean total saturated fats (39.5 ± 2.5% vs 38.5 ± 2.6%, p = 0.01). After adjusting for several patient characteristics, comorbidities, and medications, an absolute decrease of 1% in the O3I was associated with 39% greater odds of PAD (odds ratio [OR] 1.39, 95% confidence interval [CI] 1.03–1.86, and p = 0.03). PAD was associated with a deficiency of erythrocyte n-3 PUFA, a lower EPA:ARA ratio, and greater mean total saturated fats. These alterations in FA content may be involved in the pathogenesis or development of poor outcomes in PAD.     

Stigmergic cooperation of nanoparticles for swarm fuzzy control of low-density lipoprotein concentration in the arterial wall

This paper proposes the use of stigmergic cooperation between two swarms of Fuzzy Nanoparticles (FNPs) and Auxiliary Nanoparticles (ANPs) for intelligent control of Low-Density Lipoprotein (LDL) concentration in the arterial wall, as a novel non-invasive method for prevention of atherosclerosis. Given any desired fuzzy controller, a swarm of FNPs in the aqueous environment of a living tissue can collectively realize an accurate approximation of this controller, which is called swarm fuzzy controller. In this study, the task of the swarm fuzzy controller is to manipulate the pheromone level of the environment as output according to the sensed value of LDL concentration as input. Pheromone is a chemical substance that is used for stigmergic communication between two swarms of FNPs and ANPs. An ANP consists of a drug reservoir connected to a nanoscale valve which is controllable by pheromone concentration. The level of pheromone in the local environment of an ANP determines how much drug should be released by it. The hardware complexity of the proposed approach is lower than nanorobotics to facilitate its manufacturing. Simulation results on a well-known mathematical model demonstrate that this method can successfully reduce the LDL level to a desired value in the arterial wall of a patient with very high LDL level, while its performance is much better in contrast to the previous work of authors. Also, the mass of the released drug in a healthy wall is 16 times lesser than its corresponding value in an unhealthy wall.     

Gut Microbiota Community Shift with Severity of Coronary Artery Disease

Gut microbiota community shift with coronary artery disease (CAD) has been reported in several limited cohorts during the past several years. However, whether the enriched or decreased microbiota taxa with CAD can be reproducible deserves further investigation and validation. In this study, 78 human subjects were recruited. Of these, 19 were diagnosed without stenosis in coronary artery (control group, referred to herein as Ctrl), 14 with stenosis less than 50% (LT50), and 45 with stenosis greater than 50% (GT50). Fecal samples were collected and DNA was extracted to perform 16S ribosomal RNA (rRNA) gene sequencing. The operational taxonomic units (OTUs) were analyzed to identify taxa specific to different groups; next, multivariate logistic regression was employed to test whether the defined taxa could independently predict CAD risk. We found that Deltaproteobacteria, Fusobacterium, Bilophila, Actinomyces, and Clostridium XIX were enriched in Ctrl; Prevotellaceae, Parabacteriodes, and Butyricicoccus were enriched in LT50; and Roseburia and Butyricimonas were enriched in GT50. Further analysis revealed that increased populations of Deltaproteobacteria, Fusobacterium, Bilophila, and Desulfovibrionaceae were associated with a 0.26-fold, 0.21-fold, 0.18-fold, and 0.26-fold decreased risk of CAD, respectively (p < 0.05), and an increased Prevotellaceae population was associated with a 5.63-fold increased risk of CAD (p < 0.01). A combination of the 20 microbial taxa achieved an area under the receiver operating characteristic (ROC) curve of higher than 0.88 for all discriminations between LT50 vs Ctrl, GT50 vs Ctrl, LT50 + GT50 vs Ctrl, and GT50 vs Ctrl + LT50. However, the microbial taxa previously reported as enriched in CAD patients or healthy controls could not be observed in our cohort except for Bacteroides. In conclusion, CAD patients showed a different microbial taxa signature than the healthy controls. However, the non-reproducibility of the microbiota taxa enriched in CAD across different cohorts limits the use of this signature in early diagnosis and prevention. Only decreased Bacteroides abundance was found to be a reliable marker to indicate CAD progression.     

Identification of Oxidized Phosphatidylinositols Present in OxLDL and Human Atherosclerotic Plaque

Oxidized low-density lipoprotein (OxLDL) plays an important role in initiation and progression of atherosclerosis. Proatherogenic effects of OxLDL have been attributed to bioactive phospholipids generated during LDL oxidation. It is unknown what effect oxidation has on the phosphatidylinositol (PtdIns) molecules in LDL, even though PtdIns is 6% of the total LDL phospholipid pool. We sought to identify and quantitate oxidized phosphatidylinositol (OxPtdIns) species in OxLDL and human atherosclerotic plaque. Bovine liver PtdIns was subjected to non-enzymatic and lipoxygenase-catalyzed oxidation. Reversed-phase liquid chromatography with negative ESI–MS identified and confirmed compounds by fragmentation pattern analysis from which an OxPtdIns library was generated. Twenty-three OxPtdIns molecules were identified in copper-oxidized human LDL at 0, 6, 12, 24, 30, and 48 h, and in human atherosclerotic plaque. In OxLDL, OxPtdIns species containing aldehydes and carboxylates comprised 17.3 ± 0.1 and 0.9 ± 0.2%, respectively, of total OxPtdIns in OxLDL at 48 h. Hydroperoxides and isoprostanes at 24 h (68.5 ± 0.2 and 22.8 ± 0.2%) were significantly greater than 12 h (P < 0.01) without additional changes thereafter. Hydroxides decreased with increased oxidation achieving a minimum at 24 h (5.2 ± 0.3%). Human atherosclerotic plaques contained OxPtdIns species including aldehydes, carboxylates, hydroxides, hydroperoxides and isoprostanes, comprising 18.6 ± 4.7, 1.5 ± 0.7, 16.5 ± 7.4, 33.3 ± 1.1 and 30.2 ± 3.3% of total OxPtdIns compounds. This is the first identification of OxPtdIns molecules in human OxLDL and atherosclerotic plaque. With these novel molecules identified we can now investigate their potential role in atherosclerosis.     

Mechanisms of dyslipidemia of chronic renal failure

Chronic renal failure is associated with profound dysregulation of lipid metabolism and marked abnormalities of plasma lipid profile. This review is intended to provide an overview of the molecular basis of lipid disorders in chronic renal failure and explore their potential impact on cardiovascular disease and energy metabolism.     

Anthocyanidins decrease endothelin-1 production and increase endothelial nitric oxide synthase in human endothelial cells

Epidemiological and intervention studies correlate anthocyanin-rich beverages and a low incidence of coronary heart diseases. Since endothelin-1 (ET-1) and nitric oxide (NO) produced by endothelial NO synthase (eNOS) are vascular tension regulators secreted by endothelial cells, we studied the influence of two anthocyanidins, namely cyanidin (CY) and delphinidin (DP), on the regulation of ET-1 and eNOS in cultured human umbilical vein endothelial cells (HUVECs). Aglycon anthocyanidin forms, such as CY and DP, may be present in vivo after the first deglycosylation step occurring in the jejunum and in the liver. DP showed a major action compared to CY inducing a significant dose-dependent inhibitory effect on both protein and mRNA levels of ET-1. CY and DP both increased the protein level of eNOS, but DP showed the major effect raising eNOS protein in a dose-dependent manner. To correlate the vasoprotective effect of CY and DP with their antioxidant activity, we analysed also the antioxidant effect of anthocyanidins both in vitro and in HUVECs. In particular, we examined the effect of anthocyanidins on endothelial heme oxygenase-1 (HO-1), an inducible stress protein. In all tests, DP showed a higher antioxidant activity than CY. Finally, the antiproliferative effect induced by DP was detected in HUVECs. DP and CY differ in the number and position of hydroxyl groups in their structure; therefore, the greater biological activity by DP, compared with CY, seems to be due to the presence of the three hydroxyl groups on the B ring in the molecular structure of DP.     

The role of tea and tea flavonoids in cardiovascular health

Consumption of green or black tea has been inversely associated with the development and progression of cardiovascular diseases. In this review, the current knowledge about protective effects of tea and tea constituents, particularly flavonoids, on the cardiovascular system is summarized. Underlying mechanisms for the beneficial effects of tea include vasculoprotective, antioxidative, antithrombogenic, anti-inflammatory, and lipid-lowering properties of tea flavonoids. Although promising experimental data on beneficial effects of tea in various cardiovascular diseases are available, results of clinical studies in humans are not uniform. A number of factors are discussed which may contribute to inconsistent data in humans. Overall, tea represents a promising tool for the prevention and treatment of cardiovascular disorders.     

Effect of Substitution of High Stearic Low Linolenic Acid Soybean Oil for Hydrogenated Soybean Oil on Fatty Acid Intake

High stearic, low α-linolenic acid soybean oil (HSLL) has been developed via traditional breeding to serve as a substitute for partially hydrogenated soybean oils used in food manufacturing. The purpose of this study was to estimate the impact on fatty acid intake in the United States if HSLL were substituted for partially hydrogenated soybean oils used in several food categories, including baked goods, shortenings, fried foods, and margarines. Using National Health and Nutrition Examination Survey (NHANES) data (1999–2002), baseline intakes of five fatty acids and trans fatty acids (TFA) were determined at the mean and 90th percentile of fat consumption. Then intakes of these fatty acids were determined after HSLL was substituted for 100% of the partially hydrogenated soybean oils used in these four food categories. The results show that baseline intake of stearic acid is 3.0% energy at the mean and 3.3% energy at the 90th percentile. Use of HSLL could increase stearic acid intake to about 4–5% energy. Mean intakes of TFA could decrease from 2.5 to 0.9% energy, and intake of palmitic acid would remain unchanged. Use of HSLL as a substitute for partially hydrogenated soybean oils would result in changes in the fatty acid composition of the US diet consistent with current dietary recommendations.