The role of CYP1A1/2 in cholesterol ester accumulation provides a new perspective for the treatment of hypercholesterolemia

Cholesterol is an important precursor of many endogenous molecules. Disruption of cholesterol homeostasis can cause many pathological changes, leading to liver and cardiovascular diseases. CYP1A is widely involved in cholesterol metabolic network, but its exact function has not been fully elucidated. Here, we aim to explore how CYP1A regulates cholesterol homeostasis. Our data showed that CYP1A1/2 knockout (KO) rats presented cholesterol deposition in blood and liver. The serum levels of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and total cholesterol were significantly increased in KO rats. Further studies found that the lipogenesis pathway (LXRα-SREBP1-SCD1) of KO rats was activated, and the key protein of cholesterol ester hydrolysis (CES1) was inhibited. Importantly, lansoprazole can significantly alleviate rat hepatic lipid deposition in hypercholesterolemia models by inducing CYP1A. Our findings reveal the role of CYP1A as a potential regulator of cholesterol homeostasis and provide a new perspective for the treatment of hypercholesterolemia.

Study of risk factors associated with acute myocardial infarction: An observational study

Background: Cardiovascular disease has emerged as a major health burden in the developing countries. There are significant differences in the prevalence of coronary artery disease exist with respect to gender, age, and ethnicity. Aims and Objectives: This study was planned with an objective to study risk factors associated with acute myocardial infarction (AMI). Material and Methods: The descriptive present study was carried out at tertiary care hospital, intensive care unit and medicine wards, and cardiology department of tertiary care hospital. A total of 300 cases of acute coronary syndrome were included in the present study. Results: Seventy-four (52.85%) females and 56 (35%) males had hypercholesteremia. The difference was observed to be statistically significant (P = 0.0223). The decreased levels of high-density lipoprotein (HDL) cholesterol, that is, ?40 mg % were present in 52 (37.14%) females and 32 (20%) males and this difference was statistically significant (P = 0.0197). Low-density lipoprotein (LDL) cholesterol levels of ?160 mg % were present in more number of females {n = 88 (62.85%)} than males {n = 40 (25%)}. This difference was found to be statistically significant (P = 0.0001). Hypertriglyceridemia was present in 66 (47.14%) females and 44 (27.5%) males. This difference was statistically significant (P = 0.0128). Hence, the lipid profile abnormalities, namely, hypercholesteremia, hypertriglyceridemia, high LDL, and low HDL were significantly present in more numbers of females than in males. Conclusion: Risk factors for AMI such as hypertension, diabetes, family history of premature CAD, obesity, and sedentary lifestyle are more common in females than males. Smoking was risk factor in males only. Hypercholesterolemia, hypertriglyceridemia, and low LDL cholesterol are important risk factors for acute coronary syndrome in females than males.

Bioinformatics Analysis of LDLR Gene Mutation that Shed a New Light on Red Yeast Rice Monacolin K Treatment � Systematic Review

Background: Hypercholesteremia is the major cause of cardiovascular diseases. It results from elevated cholesterol levels in the blood. LDL cholesterol is removed from the circulation by using the LDL receptor. Red mold rice or red yeast rice is produced by fermentation of the Monascus Purpureus yeast on rice. Many researchers suggest that the active component in Red Yeast Rice (monacolin k) serves as a treatment for hypercholesteremic patients. Methods: By using NCBI databases, specifically GenBank to analyze DNA sequence and mRNA sequence of LDLR gene. GenBank file format was helpful to extract an accession number of the gene, number of amino acids, exons, and length of nucleotides. FASTA format was also useful to retrieve the nucleotide sequence and get the function of the protein. BLAST was used to compare the protein product of the LDLR gene between humans and pan paniscus (pygmy chimpanzee). Results: In accession number NC_000019, the number of amino acids in protein product is 44389 bp, and the number of exons found is 18. On the other hand, the gene is located in chromosome 19. The function of LDLR gene is to control the production of LDL receptor where the low-density lipoprotein particles attach to it and are taken into the cell ending up in the lysosome where the protein is degraded and cholesterol is made which will inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase that controls the production of cholesterol. Finally, many organisms have the same gene like dogs, cows, mice, rats, zebrafish, and frogs. Conclusion: Mutation in the LDLR gene causing high level of cholesterol in the blood especially LDL (Low-density Lipoprotein). Monacolin k that found in red yeast rice (RYR) is safe and natural alternative treatment for hypercholesteremic patients by lowering the cholesterol level in the blood.

Kimchi attenuates fatty streak formation in the aorta of low-density lipoprotein receptor knockout mice via inhibition of endoplasmic reticulum stress and apoptosis

BACKGROUND/OBJECTIVES: Endoplasmic reticulum (ER) stress is positively associated with atherosclerosis via elevating macrophage cell death and plaque formation, in which oxidative stress plays a pivotal role. Antioxidative, lipid-lowering, and anti-atherogenic effects of kimchi, a Korean fermented vegetable, have been established, wherein capsaicin, ascorbic acid, quercetin, 3-(4'-hydroxyl-3',5'-dimethoxyphenyl)propionic acid, and lactic acids were identified. In this study, mechanisms of action of kimchi methanol extracts (KME) on fatty streak formation via suppression of ER stress and apoptosis in aorta were examined in low-density lipoprotein receptor knockout mice. MATERIALS AND METHODS: Mice fed a high cholesterol diet with an oral administration of KME (KME group, 200 mg·kg-bw⁻¹·day⁻¹) or distilled water (control group) for 8 weeks (n = 20 for group). Plasma lipid and oxidative stress levels were evaluated. Protein expression was measured by western blot assay. Fatty streak lesion size and the degree of apoptosis were examined in the aorta. RESULTS: Compared to the control group, in the KME group, plasma lipids levels were decreased and oxidative stress was alleviated (P < 0.05). Protein expression levels of nuclear factor (erythroid-derived 2)-like 2-mediated antioxidants in aorta were increased whereas those for ER stress markers, glucose regulated protein 78, phospho-protein kinase RNA-like ER kinase, phospho-eukaryotic initiation factor 2 subunit α, X-box binding protein 1, and C/EBP homologous protein were decreased in the KME group (P < 0.05). Moreover, apoptosis was suppressed via downregulation of phospho-c-Jun N-terminal kinase, bcl-2-associated X protein, caspases-9, and -3 with a concomitant upregulation of anti-apoptotic protein, B-cell lymphoma 2 (P < 0.05). Fatty streak lesion size was reduced and the degree of apoptosis was less severe in the KME group (P < 0.05). CONCLUSIONS: In conclusion, antioxidant activity of KME might prevent fatty streak formation through, in part, inhibition of ER stress and apoptosis in aortic sinus where macrophages are harbored.

Effect of atorvastatin on tau protein phosphorylation in hippocampus of hypercholesteremic mouse / 中华老年医学杂志

Objective To investigate the phosphorylation of tau protein and the effect of atorvastatin on tau protein phosphorylation in hypercholesteremic mouse hippocampus. Methods Male Kunming mice were randomly divided into normal control group, hypercholesteremia group, and low-dose atorvastatin treatment group (8mg·kg-1·d-1), middle-dose group (15mg·kg-1·d-1),and high-dose group (20mg·kg-1·d-1) with five mice in each group. The hypercholesteremia mouse model was induced by cholesterol-enriched diets. The expression level of tau protein phosphorylation in mouse hippocampus was detected by Western blot and immunohistochemistry methods. The activities of mitogen-activated protein kinase (MAPK) and cyelin dependent kinase 5 (Cdk-5) were measured by liquid scintillation counting of the hippocampus incorporated radioactivity and immunoprecipetation activity assay respectively. Results In hypercholesteremic group, the expression level of tau protein phosphorylation in mouse hippocampus was significantly increased(F=14.761,P＜0.01)as compared with control group, and so were MAPK activity and Cdk-5 activity(all P＜0.01). Atorvastatin treatment group showed the decreased expression level of tau protein phosphorylation at ser396/404 site in low-dose group (F=6.349,P＜0.05),middle-dose group (F=10.283,P＜0.01) and high-dose group (F=10.511,P＜0.01) as compared with hypercholesteremia mouse group. The activities of MAPK and Cdk-5 were decreased along with the increasing atorvastatin doses. Conclusions Hypercholesteremia induces tau protein hyperphosphorylation in mouse hippocampus. Abnormal cholesterol metabolism may play an important role in the pathology process of neurodegeneration in brain. Atorvastatin might inhibit tau protein hyperphosphorylation by inhibiting the activations of MAPK and Cdk-5 in brain, atorvastatin may have the protect effect for tau protein.

Motor function changes of sphincter of Oddi in rabbits with hypercholesteremia / 中华消化外科杂志

Objective To investigate the effects of hypercholesteremia on the motor function of sphincter of Oddi (SO). Methods Thirty-two rabbits were divided into control group and experimental groups. In the control group, the rabbits were fed with normal diet. In the experimental groups, the rabbits were fed with normal diet + cholesterol for 4, 6 and 10 weeks. Myoelectric activity and pressures of SO were detected. All data were analyzed by t test. Results The serum total cholesterol and low density lipoprotein cholesterol were at a high level in rabbits which were fed with normal diet + cholesterol for 10 weeks (t=9.63, 11.38, P <0.05); basal pressure, pike pressure and amplitude of SO were significantly elevated (t=5.23, 6.34, 3.24, P < 0.05) ; the spike potential of SO changed to myoelectronic activity, with prolonged time period of myoelectronic activity, while the discharge rate was decreased (t=13.68, 10.18, P < 0.05). Conclusion Hypercholesteremia may change the motor function of SO and enhance its peristalsis to speed up the excretion of bile.

INFLUENCE OF EXPERIMENTAL ATHEROSCLEROSIS ON SERUM COPPER, ZINC, CHROMIUM, MANGANESE, AND SELENIUM / 营养学报

0.05) but a statistically significant negative correlation was noted between serum cholesterol and zinc (r= -0.9986, P

INFLUENCES OF KONJAC-POLYSACCHARIDE ON THE LEVELS OF TISSUE LIPIDS AND FOUR INORGANIC ELEMENTS IN RATS / 营养学报

This paper reports a study regarding the verity of the hypocholestero-lemic effect of konjac-polysaccharide. The konnyaku powder (KP) used in this study was prepared and refined from the tubers of Amorphophallus ko-njac K. Koch and contained 84.8% of glucomannan. Male and female Spra-ue-Dawley rats aged 5 weeks were divided into 5 groups and fed on normal basal diet, hypercholesterolemic diet (control diet) and 3 test diets (i.e. KP was added to the control diet at a dosage of 2.5%, 5% or 10%) respe- ctively, for 12 weeks.The results obtained from this study showed that KP could markedly lower the level of the cholesterol in sera and livers of rats feeding hyper-cholesterolemic diets. At the end of the 4th week of the feeding experiment, the serum cholesterol level of the 5% and the 10% KP groups, and the liver cholesterol level of the 10% KP group were shown to be significantly lower than those of the control group. At the end of the 12th week, serum cholesterol levels of all the 3 KP groups were found to be lowered to the level of the normal group and so did the liver cholesterol level of the 10% KP group. The lipotropic (anticholesteatosis) effect of KP was also confirmed by the hepatic histopathological examination. Besides the hypocholest-eroletmic eftect, KP diets can also increase the bulk of stool. Finally, there were not any harmful effects on the absorption and utilization of Ca, Fe, Zn and Cu being found.