Distinct chemical changes in abdominal but not in thoracic aorta upon atherosclerosis studied using fiber optic Raman spectroscopy

Fiber optic Raman spectroscopy and Raman microscopy were used to investigate alterations in the aorta wall and the surrounding perivascular adipose tissue (PVAT) in the murine model of atherosclerosis (Apoe-/-/Ldlr-/- mice). Both abdominal and thoracic parts of the aorta were studied to account for the heterogenic chemical composition of aorta and its localization-dependent response in progression of atherosclerosis. The average Raman spectra obtained for both parts of aorta cross sections revealed that the chemical composition of intima-media layers along aorta remains relatively homogeneous while the lipid content in the adventitia layer markedly increases with decreasing distance to PVAT. Moreover, our results demonstrate that the increase of the lipid to protein ratio in the aorta wall correlates directly with the increased unsaturation level of lipids in PVAT and these changes occur only in the abdominal, but not in thoracic, aorta. In summary, distinct pathophysiological response in the aortic vascular wall could be uncovered by fiber optic Raman spectroscopy based on simple parameters detecting chemical contents of lipids in PVAT

Multi-omic signatures of atherogenic dyslipidaemia : pre-clinical target identification and validation in humans

Dyslipidaemia is a major risk factor for atherosclerosis and cardiovascular diseases. The molecular mechanisms that translate dyslipidaemia into atherogenesis and reliable markers of its progression are yet to be fully elucidated. To address this issue, we conducted a comprehensive metabolomic and proteomic analysis in an experimental model of dyslipidaemia and in patients with familial hypercholesterolemia (FH)

HHIPL1, a Gene at the 14q32 Coronary Artery Disease Locus, Positively Regulates Hedgehog Signaling and Promotes Atherosclerosis

The research leading to these results has received funding from the European Union Seventh Framework Programme FP7/2007–2013 under grant agreement number HEALTH-F2-2013–601456, a Transatlantic Networks of Excellence Award (12CVD02) from The Leducq Foundation and the British Heart Foundation (SP/18/8/33620) as a partner of the European Research Area Network on Cardiovascular Diseases (ERA-CVD) druggable-MI-genes (01KL1802) and supported by the UK National Institute for Health Research (NIHR) Leicester Biomedical Research Centre. Dr Samani is a UK NIHR Senior Investigator. Drs Morris, Ye, and Webb are funded by the British Heart Foundation (SP/16/4/32697).Peer reviewedPublisher PD

Effect of conjugated linoleic acid and different type of dietary fat on serum lipid profile, liver enzymes activity and oxidative stress markers in Wistar rats

Background. Nutritional recommendations emphasize the need to limit consumption of saturated fatty acids and to increase the intake of polyunsaturated fatty acids in the prevention of non-communicable chronic diseases, particularly cardiovascular diseases. Among the fatty acids with health-related effects on the body, conjugated fatty acids are mentioned (i.e. CLA). Objective. The current study was designed to determine the effects of conjugated linoleic acid (CLA) on serum lipid profile, glucose, liver enzymes activity (AST and ALT), malonic dialdehyde (MDA) as well as lipid hydroperoxide (LPO) concentrations in rats fed diet differing in type of dietary fat. Material and methods. Male Wistar rats were divided into six groups and fed the following diets: control AIN-93G diet contained soybean oil (O) and diets with modification of fat source: butter (B) and margarine (M). The experimental diets were supplemented with 1% of conjugated linoleic acid (O+CLA, B+CLA, M+CLA). After 21 days the blood was collected and lipid profile, glucose, liver enzymes, MDA as well as LPO were analyzed. Results. The dietary treatments had no significant effect on the body weight and liver weight of the animals. The concentrations of total cholesterol (TC) and LDL+VLDL cholesterol were unchanged. Both experimental factors (fat source and CLA) had a significant influence on the TAG and HDL levels. Margarine (M) significantly increased the TAG concentration, whereas CLA had a significant impact on the TAG reduction (M+CLA). Glucose level was significantly decreased in all groups fed diets supplemented with CLA. Serum ALT significantly increased in all CLA groups. Fat source had statistically significant influence on the MDA concentration. The LPO level was significantly elevated in all CLA groups. There was statistically significant interaction of experimental factors (fat source and CLA supplementation) on LPO level. Conclusions. Margarine had an adverse effect on the rat’s lipid profile. However, in the group fed with margarine, the addition of CLA decreased the concentration of TAG. Regardless of the type of the dietary fat, CLA supplementation increased the level of LPO in the blood serum of animals

Effect of low carbohydrate high protein (LCHP) diet on lipid metabolism, liver and kidney function in rats

The objective of this study was to compare effects of Western diet (WD) with low carbohydrate high protein (LCHP) diet on lipid metabolism, liver and kidney function in rats. Eighteen rats were randomly assigned to three experimental groups and fed for the next 2 months. The experimental diets were: Control (7% of soybean oil, 20% protein), WD (21% of butter, 20% protein), and LCHP (21% of butter and 52.4% protein) diet. The LCHP diet significantly decreased the body weight of the rats. Diet consumption was differentiated among groups, however significant changes were observed since third week of the experiment duration. Rats fed LCHP diet ate significantly less (25.2. g/animal/day) than those from Control (30.2. g/animal/day) and WD (27.8. g/animal/day) groups. Additionally, food efficiency ratio (FER) tended to decrease in LCHP fed rats. Serum homocysteine concentration significantly decreased in rats fed WD and LCHP diets. Liver weights were significantly higher in rats fed WD and LCHP diets. At the end of the experiment (2 months) the triacylglycerol (TAG) was significantly decreased in animals fed LCHP compared to WD. qRT-PCR showed that SCD-1 and FAS were decreased in LCHP fed rats, but WD diet increased expression of lipid metabolism genes. Rats receiving LCHP diet had two fold higher kidney weight and 54.5% higher creatinin level compared to Control and WD diets. In conclusion, LCHP diet decreased animal's body weight and decreased TAG in rat's serum. However, kidney damage in LCHP rats was observed

Anti-atherosclerotic activity of catechins depends on their stereoisomerism

In terms of stereochemistry, catechins are divided into two groups: (-) epi forms (2R, 3R) and (-) forms (2S, 3R). Most of the catechins present in green tea are (-) epi forms (2R, 3R). Under the influence of high temperatures, in anaerobic conditions, as a result of epimerization the proportion of the (-) form (2S, 3R) increases. The data indicate that the presence of thermally modified catechins in the diet more efficiently reduces the development of atherosclerosis in apoE knockout mice than the presence of native catechins. The addition of the thermally modified formulations to the high-fat diet resulted in a reduction of the area of atherosclerotic lesions by about 28% (en face method) and 45% (cross-section method) compared to the group fed the high-fat diet without catechins. Furthermore, the body weight gain and plasma TBARS concentration in mice fed a diet with the addition of catechins depends on the degree of epimerization of catechins and decreases with increasing content of catechins belonging to the (-) form (2S, 3R). Moreover, plasma HDL cholesterol concentration in mice depends on catechins' stereoisomerism and increases along with the increasing content of catechins belonging to the (-) form (2S, 3R)

Pomegranate Seed Oil as a Source of Conjugated Linolenic Acid (CLnA) Has No Effect on Atherosclerosis Development but Improves Lipid Profile and Affects the Expression of Lipid Metabolism Genes in apoE/LDLR^−/− Mice

The aim of this study was to evaluate the anti-atherosclerotic effect of pomegranate seed oil as a source of conjugated linolenic acid (CLnA) (cis-9,trans-11,cis-13; punicic acid) compared to linolenic acid (LnA) and conjugated linoleic acid (CLA) (cis-9,trans-11) in apoE/LDLR−/− mice. In the LONG experiment, 10-week old mice were fed for the 18 weeks. In the SHORT experiment, 18-week old mice were fed for the 10 weeks. Diets were supplied with seed oils equivalent to an amount of 0.5% of studied fatty acids. In the SHORT experiment, plasma TCh and LDL+VLDL cholesterol levels were significantly decreased in animals fed CLnA and CLA compared to the Control. The expression of PPARα in liver was four-fold increased in CLnA group in the SHORT experiment, and as a consequence the expression of its target gene ACO was three-fold increased, whereas the liver’s expression of SREBP-1 and FAS were decreased in CLnA mice only in the LONG experiment. Punicic acid and CLA isomers were determined in the adipose tissue and liver in animals receiving pomegranate seed oil. In both experiments, there were no effects on the area of atherosclerotic plaque in aortic roots. However, in the SHORT experiment, the area of atherosclerosis in the entire aorta in the CLA group compared to CLnA and LnA was significantly decreased. In conclusion, CLnA improved the lipid profile and affected the lipid metabolism gene expression, but did not have the impact on the development of atherosclerotic plaque in apoE/LDLR−/− mice