Reduced Serum Cholesterol Levels Research Articles

Effect of green tea on serum cholesterol level in cholesterol fed rabbits

Background: Since the development of atherosclerosis involves dyslipidemia, we postulated that green tea may exert lowering of serum cholesterol levels. Objectives: To investigate the effects of green tea on serum cholesterol level. Methods: Total 45 rabbits (15 were fed on 1% cholesterol and green tea for 16 weeks, another 15 were fed on 1% cholesterol and plain water for 16 weeks, last batch of 15 rabbits received normal rabbit diet for 16 weeks) in the department of Cardiac Surgery, Bangabandhu Sheikh Mujib Medical University, Dhaka from April 2011 to September 2012.They were evaluated for lipid profile and presence of atherosclerosis. Results: The mean total cholesterol in cholesterol fed rabbits with green tea after 16 weeks was 21.06 ± 5.55, LDL-C was 20.80 ± 6.16, Serum TG was 153.67 ± 33.59, HDL-C neither increased nor decreased. The mean total cholesterol in cholesterol fed rabbits with plain water after 16 weeks was 27 .53 ± 5.15, LDL-C was 32.40 ± 8.24 and TG was 290.13 ± 44.31, no effect were seen on HDL-C. These rabbits were fed on green tea for 8 weeks, cholesterol levels returned to levels at commencement of experiment. Rabbits fed on normal rabbit diet for 16 weeks had TC l9.20 ± 4.85, LDL-C was 19.20 ± 2.04 and TG was 155.06 ± 32.03 mg/dl. HDL-C remained in normal range. But there was no atheroschlerotic change in any group. Conclusion: Green tea significantly reduces serum cholesterol levels in cholesterol fed rabbits. There was no effect of green tea on HDL-C in any group.

Micro-Heterogeneity and Micro-Rheological Properties of High-Viscosity Barley β-Glucan Solutions Studied by Diffusing Wave Spectroscopy (DWS)

Soluble fiber β-glucan is one of the key dietary materials in healthy food products known for reducing serum cholesterol levels. The micro-structural heterogeneity and micro-rheology of high-viscosity barley β-glucan solutions were investigated by the diffusing wave spectroscopy (DWS) technology. By comparing the mean-square displacement (MSD) of the microspheres imbedded in eight concentrations of β-glucan solutions, we found that the solutions exhibited nearly homogeneous behavior at ≤0.1 %, but the material showed a clear degree of heterogeneity at ≥0.25 %. Micro-rheology investigation revealed that β-glucan solutions displayed nearly perfect viscous behavior at ≤0.1 %, but the property changed into viscoelastic one at ≥0.25 %. The magnitude of high-frequency viscoelastic moduli for the 0.25 % - 0.75 % β-glucan solutions can be characterized by ׀G*׀ ∝ ω3/4, which is the semi-flexible polymer behavior. However, the magnitude of high-frequency viscoelastic moduli (׀G*׀) for the 1.0 % - 1.25 % β-glucan solutions is proportional to ω1/2, which is the flexible polymer behavior. All micro-structural heterogeneity and micro-rheological property shifts occurred in relatively small concentration ranges.

Association between prediagnostic glucose, triglycerides, cholesterol and meningioma, and reverse causality.

Background:Although meningioma is a benign tumour, it may cause significant morbidity. Obesity and diabetes are positively associated with meningioma. To evaluate the potential effects of obesity-related prediagnostic glucose, triglycerides and cholesterol on meningioma and of prediagnostic meningioma on these biomarkers, we conducted a cohort study.Methods:We identified 41 355 individuals in the Apolipoprotein MOrtality RISk cohort with values for these biomarkers within 15 years before meningioma diagnosis, death, migration or the end of follow-up. We then estimated hazard ratios (HRs) and their interactions with time and age using Cox regression.Results:Meningioma was diagnosed in 181 women and 115 men whose median follow-up time was 7 years. Fasting serum glucose level was inversely related to meningioma among women (Ptrend=0.0006) but not men (Ptrend=0.24). Prediagnostic diabetes was inversely related to meningioma in both sexes combined (HR=0.45, 95% confidence interval (CI) 0.29-0.71), as was serum cholesterol within the year before diagnosis (HR=0.50, 95% CI 0.34-0.72).Conclusions:Paradoxically, hyperglycaemia is inversely associated with meningioma in women. This finding does not necessarily negate the positive role of obesity or diabetes in meningioma development; rather, it may indicate that their effects depend on the stage of development. Furthermore, the prediagnostic tumour may reduce serum cholesterol levels.

Changes in Serum Cholesterol and Diet in North Karelia and All Finland

Finland in the 1960s, and especially North Karelia in the eastern part of the country, had the highest cardiovascular mortality in the world. The classical cardiovascular risk factors were all common, but serum cholesterol level was extremely high because of the very high intake of saturated fats, mainly from dairy products. The North Karelia Project was started as a comprehensive preventive program to reduce serum cholesterol levels by reducing the intake of saturated fats and increasing the intake of polyunsaturated fats in the whole population. Cross-sectional population surveys were done in North Karelia and nearby Kuopio province every 5 years starting in 1972. After 1982, surveys were started in 2 other areas. Blood cholesterol was measured from serum samples, and diet was assessed by a questionnaire in all surveys-since 1982 by 3-day food record, since 1997 by 24-hour recall, and since 2002 by 48-hour recall. Between 1972 and 2012, the population in North Karelia reduced serum cholesterol from 6.92 mmol/l to 5.46 mmol/l (21%) in men and from 6.81 mmol/l to 5.37 mmol/l (21%) in women. In men, serum cholesterol level reduced more in North Karelia than in the reference province of Kuopio during the first 5 years from 1972 to 1977. Since that time, changes in serum cholesterol level have been very similar in different parts of the country. Saturated fats were reduced from 20% of energy intake to 12% in 2007 but increased from 2007 to 2012 to 14%. In conclusion, serum cholesterol reduction by dietary changes is feasible on the population level but requires active work and large-scale cooperation between all the meaningful sectors in the society.

Soy milk powder supplemented with phytosterol esters reduced serum cholesterol level in hypercholesterolemia independently of lipoprotein E genotype: a random clinical placebo-controlled trial

Phytosterols (PSs) are reported to lower the serum total cholesterol and low-density lipoprotein cholesterol concentrations enriched in some fatty foods, such as margarine. However, these high-fat foods are not very suitable for older people. Soy milk is the favorite food for elderly people in China; therefore, we hypothesized that the consumption of soy milk powder supplemented with PSs would decrease the serum cholesterol levels in older Chinese people independent of the genotypes of apolipoprotein E (ApoE). Mild to moderate hyperlipidemic patients (n = 170) were recruited from different communities and treated with placebo soy milk powder or 3.4 g PS esters–enriched soy milk powder (2.0 g/d free PS in 30 g soy milk powder). The fasting serum lipid profiles at the baseline and after 3 and 6 months of intervention were measured. The ApoE genotype was also determined. After 3 months of PS intervention, the serum lipid profile was not changed significantly in either group. The serum total cholesterol, low-density lipoprotein cholesterol, and non– high-density lipoprotein cholesterol levels decreased by 9.3%, 11.4%, and 12.6%, respectively, in the PS group at the end of the intervention (6 months) compared with the control group, whereas the serum high-density lipoprotein cholesterol and triglyceride levels were not affected significantly. In the PS group, both the ApoE3 and ApoE4 carriers had a similar response to PS consumption. These findings suggested that PS-fortified soy milk powder was effective in lowering the serum cholesterol levels in older Chinese volunteers with mild to moderate hypercholesterolemia in both the ApoE3 and ApoE4 carriers.

Metabolic and reproductive parameters in prepubertal gilts after omega-3 supplementation in the diet

Polyunsaturated fatty acids may benefit reproductive performance of female swine. This study evaluated metabolic and reproductive parameters of prepubertal finishing gilts fed with fish oil as a natural source of omega-3 fatty acids (6.88g/d) (n=12) over a period of 45 d. Gilts in the control group were fed soybean oil (n=13). Body weight and backfat were determined at 15-d intervals. Serum levels of leptin, IGF-1, insulin, cholesterol and triglycerides were measured at the beginning (D0) and at the end of the period (D45). Immunolabeling intensity for leptin and its receptor (ObRb) was assessed in oocytes of preantral follicles. Gilts fed omega-3 presented slightly heavier uteri (P=0.09) than control gilts, but there was no effect on body weight and backfat (P>0.05). Cholesterol serum levels tended to be lower at D45 for omega-3 supplemented gilts than for controls (P=0.06). Triglycerides and IGF-1 serum levels were lower at D45 than at D0 for control gilts (P<0.05), but unaltered for supplemented gilts. Insulin levels were unaffected by supplementation (P>0.05), but were greater at D45 than at D0 in both treatments (P<0.05). Immunolabeling for leptin and ObRb in oocytes included in preantral follicles was more intense for supplemented gilts than for control gilts (P<0.05). Omega-3 supplementation was associated with reduced serum cholesterol level and more intense staining for leptin in oocytes of prepubertal gilts, which suggests some involvement on triggering puberty.

Pleiotropic effects of statins: new therapeutic targets in drug design.

The HMG Co-enzyme inhibitors and new lipid-modifying agents expand their new therapeutic target options in the field of medical profession. Statins have been described as the most effective class of drugs to reduce serum cholesterol levels. Since the discovery of the first statin nearly 30years ago, these drugs have become the main therapeutic approach to lower cholesterol levels. The present scientific research demonstrates numerous non-lipid modifiable effects of statins termed as pleiotropic effects of statins, which could be beneficial for the treatment of various devastating disorders. The most important positive effects of statins are anti-inflammatory, anti-proliferative, antioxidant, immunomodulatory, neuroprotective, anti-diabetes, and antithrombotic, improving endothelial dysfunction and attenuating vascular remodeling besides many others which are discussed under the scope of this review. In particular, inhibition of Rho and its downstream target, Rho-associated coiled-coil-containing protein kinase (ROCK), and their agonistic action on peroxisome proliferator-activated receptors (PPARs) can be viewed as the principle mechanisms underlying the pleiotropic effects of statins. With gradually increasing knowledge of new therapeutic targets of statins, their use has also been advocated in chronic inflammatory disorders for example rheumatoid arthritis (RA) and in systemic lupus erythematosus (SLE). In the scope of review, we highlight statins and their pleiotropic effects with reference to their harmful and beneficial effects as a novel approach for their use in the treatment of devastating disorders. Graphical abstract Pleiotropic effect of statins.

Hypoxia-Inducible Factor Prolyl 4-Hydroxylase-2 Inhibition Protects Against Development of Atherosclerosis.

Small-molecule hypoxia-inducible factor prolyl 4-hydroxylase (HIF-P4H) inhibitors are being explored in clinical studies for the treatment of anemia. HIF-P4H-2 (also known as PHD2 or EglN1) inhibition improves glucose and lipid metabolism and protects against obesity and metabolic dysfunction. We studied here whether HIF-P4H-2 inhibition could also protect against atherosclerosis. Atherosclerosis development was studied in low-density lipoprotein (LDL) receptor-deficient mice treated with an oral HIF-P4H inhibitor, FG-4497, and in HIF-P4H-2-hypomorphic/C699Y-LDL receptor-mutant mice, all mice being fed a high-fat diet. FG-4497 administration to LDL receptor-deficient mice reduced the area of atherosclerotic plaques by ≈50% when compared with vehicle-treated controls and also reduced their weight gain, insulin resistance, liver and white adipose tissue (WAT) weights, adipocyte size, number of inflammation-associated WAT macrophage aggregates and the high-fat diet-induced increases in serum cholesterol levels. The levels of atherosclerosis-protecting circulating autoantibodies against copper-oxidized LDL were increased. The decrease in atherosclerotic plaque areas correlated with the reductions in weight, serum cholesterol levels, and WAT macrophage aggregates and the autoantibody increase. FG-4497 treatment stabilized HIF-1α and HIF-2α and altered the expression of glucose and lipid metabolism and inflammation-associated genes in liver and WAT. The HIF-P4H-2-hypomorphic/C699Y-LDL receptor-mutant mice likewise had a ≈50% reduction in atherosclerotic plaque areas, reduced WAT macrophage aggregate numbers, and increased autoantibodies against oxidized LDL, but did not have reduced serum cholesterol levels. HIF-P4H-2 inhibition may be a novel strategy for protecting against the development of atherosclerosis. The mechanisms involve beneficial modulation of the serum lipid profile and innate immune system and reduced inflammation.

Dyslipidaemia in 2015: Advances in treatment of dyslipidaemia.

Statins remain the first-line therapy for dyslipidaemia. In 2015, however, effectiveness in reducing serum cholesterol levels and decreasing rates of cardiovascular disease in combination with statins has been demonstrated for two new classes of drugs: cholesterol-absorption inhibitors and PCSK9 inhibitors. The latter rival statins in their capacity to lower cholesterol levels.

From the Editor’s desk....: January 2016

Selection of the month Plasma exchange improves survival of ALF patients and liver derived exosomes can improve hepatic regeneration Despite improvements in our understanding of acute liver failure, mortality of patients without liver transplantation remains unacceptably high. The study of Larsen et al. describes the results of a landmark randomized clinical trial that took over 10-years to perform and shows that treatment with plasma exchange can improve the survival of ALF patients , providing proof of concept for ‘detoxification' systems.

Abstract 17586: HSP27 Mediated Atheroprotection Requires GM-CSF Induction: Potential Role in Reverse Cholesterol Transport? (Best of Basic Science Abstract)

Introduction: Previously, we demonstrated that Heat Shock Protein 27 (HSP27) reduces experimental atherogenesis and patients with elevated serum HSP27 levels are relatively protected against future CV events. We previously reported that extracellular HSP27 activates the NF-kB pathway and increases the expression of GM-CSF. While the potential atheroprotective role of GM-CSF remains controversial, clinical reports highlight its effect on reducing serum cholesterol levels. We now hypothesize that GM-CSF plays an important role in HSP27-mediated atheroprotection, potentially by up-regulating reverse cholesterol transport (RCT). Methods / Results: 1. NF-KB signaling in vitro: Treatment of macrophages with recombinant HSP27 (rHSP27) activated NF-kB 15-fold via TLR-4 (NF-kB reporter gene assay; controls: truncated rHSP27 peptide and TLR-4 deficient cells; p&lt;0.05). While rHSP27 substantially induced GM-CSF expression and secretion (300- and 400-fold respectively; p&lt;0.05) both processes were blocked by NF-kB inhibitors. 2. In vivo role of GM-CSF induction in HSP27-mediated atheroprotection: Aortic atherogenesis in apoE null treated with rHSP27 was reduced by an expected 40%, while ApoE null / GM-CSF null did not respond to rHSP27 treatment. Moreover, apoE null / GM-CSF null macrophages expressed ~33% lower levels of the reverse cholesterol transporters, ABC-A1 and ABC-G1. 3. rHSP27 &amp; Reverse Cholesterol Transport: THP-1 macrophages pre-treated with oxLDL and incubated with rHSP27 for 24h showed enhanced mRNA and protein expression of ABCA1 and ABCG1 (p&lt;0.01). In a RCT assay, THP-1 macrophages labeled with NBD-cholesterol and treated with rHSP27 for 24h before being incubated with apoA1 or HDL showed increased cholesterol efflux compared to controls (p&lt;0.0001 for both). Conclusion: HSP27 up regulates expression of GM-CSF that appears to play an important role in RCT-mediated atheroprotection.

Involvement of microRNA214 and transcriptional regulation in reductions in mevalonate pyrophosphate decarboxylase mRNA levels in stroke-prone spontaneously hypertensive rat livers.

Hypocholesterolemia has been epidemiologically identified as one of the causes of stroke (cerebral hemorrhage). We previously reported that lower protein levels of mevalonate pyrophosphate decarboxylase (MPD), which is responsible for reducing serum cholesterol levels in stroke-prone spontaneously hypertensive rats (SHRSP), in the liver were caused by a reduction in mRNA levels. However, the mechanism responsible for reducing MPD expression levels in the SHRSP liver remains unclear. Thus, we compared microRNA (miR)-214 combined with the 3'-untranslated region of MPD mRNA and heterogeneous nuclear RNA (hnRNA) between SHRSP and normotensive Wistar Kyoto rats (WKY). miR-214 levels in the liver were markedly higher in SHRSP than in WKY, whereas hnRNA levels were significantly lower. These results indicate that the upregulation of miR-214 and downregulation of MPD transcription in the liver both play a role in the development of hypocholesterolemia in SHRSP.

Effects of methanolic fruit extract of Solanum macrocarpum L. (Solanaceae) on biochemical profile of albino rats (Rattus norvegicus)

The effects of methanolic fruit extract of Solanum macrocarpum on the biochemical parameters of normal albino rats were investigated for 21 days. Forty-eight (48) adult male albino rats were divided into a control group (A) and three treatment groups (B, C and D) of 12 rats each. Each group was further divided into three replicates of four rats each. Groups B, C and D received daily oral administration of the extract at doses of 400, 800 and 1600 mg/kg of body weight (bw), respectively, while the control group received distilled water for 21 days. Blood samples were collected before the start of experimentation (week 0) and thereafter at weekly intervals from one rat per replicate. Biochemical parameters of the blood samples were determined using bioassay. All the treatment groups showed a progressive significant reduction in serum total cholesterol levels from week 0 to week 3. Similarly, there was significant decrease (p 0.05) in aspartate transaminase (AST), a significant decrease (p 0.05) in bilirubin. There was non-significant decrease in albumin levels of the treated rats across weeks, while total protein showed a non-significant increase. The urea and blood urea nitrogen (BUN) and creatinine levels of the treated rats showed an overall non-significant (p > 0.05) increase. This study suggests that methanolic fruit extract of S. macrocarpum may be useful in reducing serum cholesterol levels.

Rho-GTPase and Atherosclerosis: Pleiotropic Effects of Statins.

3‐Hydroxy‐methylglutaryl‐coenzyme A (HMG‐CoA) reductase inhibitors or statins are a class of medications with potent effects on reducing serum cholesterol level, and currently have been widely used in the primary and secondary prevention of atherosclerotic cardiovascular diseases (ASCVD).

Cognitive function and left ventricular assist device implantation

Cognitive impairment is frequent in patients with heart failure (HF) and can lead to poor quality of life and increased risk of mortality. The Montreal Cognitive Assessment (MoCA) is a simple screening tool that is sensitive to mild cognitive impairment (MCI) and that has been validated in the settings of neurologic and cardiovascular disease. This study determined the extent of cognitive impairment in patients with HF undergoing evaluation for advanced surgical therapy and evaluated changes in MoCA score with follow-up cognitive assessment at 8 months after left ventricular assist device (LVAD) implantation. As part of routine assessment for LVAD candidacy, 176 patients with advanced HF were administered the MoCA; 56 patients were reevaluated 8 months after LVAD implantation. Patients with MCI, indicated by MoCA score <26 out of 30, made up 67% of the study cohort. MCI was associated with significantly older age, higher CHADS2 (congestive HF, hypertension, age >75 years, diabetes mellitus, prior stroke or transient ischemic attack) risk score, statin use, history of stroke and hypertension, and reduced serum cholesterol levels. In 56 patients who underwent follow-up evaluation after LVAD implantation, total MoCA score and visuospatial, executive, and delayed recall cognitive domains were significantly improved. This study assessed the use of the MoCA in patients with end-stage HF being evaluated for advanced surgical therapy. We found the MoCA to be a rapid, simple, and powerful tool for detecting cognitive impairment in these patients. MCI was highly prevalent in the cohort. Significant improvement in overall MoCA score was noted after LVAD implantation.

Fructo-oligosaccharide effects on serum cholesterol levels. An overview.

To address the effects of fructooligosaccharides (FOS) intake on serum cholesterol levels. We performed a search for scientific articles in MEDLINE database from 1987 to 2014, using the following English keywords: fructooligosaccharides; fructooligosaccharides and cholesterol. A total of 493 articles were found. After careful selection and exclusion of duplicate articles 34 references were selected. Revised texts were divided into two topics: "FOS Metabolism" and "FOS effects on plasma cholesterol." The use of a FOS diet prevented some lipid disorders and lowered fatty acid synthase activity in the liver in insulin-resistant rats. There was also reduction in weight and total cholesterol in beagle dogs on a calorie-restricted diet enriched with short-chain FOS. Another study found that 2g FOS daily consumption increased significantly serum HDL cholesterol levels but did not ensure a significant reduction in levels of total cholesterol and triglycerides.. Patients with mild hypercholesterolemia receiving short-chain FOS 10.6g daily presented no statistically significant reduction in serum cholesterol levels. However, when FOS was offered to patients that changed their lifestyle, the reduction of LDL cholesterol and steatosis was higher. Fructooligosaccharides intake may have a beneficial effect on lipid metabolism and regulation of serum cholesterol levels in individuals that change their lifestyle. FOS supplementation use in diets may therefore be a strategy for lowering cholesterol.

Cholesterol-lowering effect of rice bran protein containing bile acid-binding proteins.

Dietary plant protein is well known to reduce serum cholesterol levels. Rice bran is a by-product of rice milling and is a good source of protein. The present study examined whether feeding rats a high-cholesterol diet containing 10% rice bran protein (RBP) for 10 d affected cholesterol metabolism. Rats fed dietary RBP had lower serum total cholesterol levels and increased excretion of fecal steroids, such as cholesterol and bile acids, than those fed dietary casein. In vitro assays showed that RBP strongly bound to taurocholate, and inhibited the micellar solubility of cholesterol, compared with casein. Moreover, the bile acid-binding proteins of the RBP were eluted by a chromatographic column conjugated with cholic acid, and one of them was identified as hypothetical protein OsJ_13801 (NCBI accession No. EAZ29742) using MALDI-TOF mass spectrometry analysis. These results suggest that the hypocholesterolemic action of the RBP may be caused by the bile acid-binding proteins.

Dietary high-polyphenols extra-virgin olive oil is effective in reducing cholesterol content in eggs.

BackgroundExtra-virgin olive oil (EVOO) represents an important food in Mediterranean diet due to its favorable effects on human and animal health derived from the consumption of polyphenols. We studied the effects of dietary EVOO differing in polyphenols levels on egg quality.MethodsA total of 150 laying hens were allotted into three groups over 10 weeks of the experimental period. The three diets were based on wheat-soybean meal with added oils at 2.5%. Hens were fed the following diets: (1) commercial diet containing sunflower oil (Control), (2) diet EVOO from Cima di Bitonto variety (low-polyphenols content; Low-P), and (3) diet EVOO from Coratina variety (high-polyphenols content; High-P). The performance of the hen, the qualitative traits of eggs, and the fatty acid composition and cholesterol content of egg-yolk were measured.ResultsNone of the egg productive parameters studied were influenced by dietary treatment, except for yolk color score that was enhanced in hens fed the both EVOO diets (P < 0.05). Feeding high-polyphenols EVOO reduced serum cholesterol level in hens (P < 0.01) and egg-yolk cholesterol levels (as per egg; P < 0.05). The dietary supplementation of high-polyphenols EVOO raised the polyunsaturated fatty acids (PUFAs) composition and increased the content of oleic and linolenic acids in egg-yolk. Moreover, the atherogenic index in egg-yolk decreased linearly in accordance with increasing levels of dietary polyphenols (P < 0.01).ConclusionIn conclusion, a diet for hens consisting of high-polyphenols level from extra-virgin olive oil can improve the fatty acid quality of egg-yolk while lowering the egg-yolk cholesterol level, which could be a beneficial functional food for human health.

Cholesterol-lowering effects of a putative probiotic strain Lactobacillus plantarum EM isolated from kimchi

Lactobacillus plantarum EM, which was isolated from kimchi, showed high cholesterol removal by growing, resting, and even dead cells. Moreover, cell wall fraction of L. plantarum EM removed cholesterol in a cell wall concentration-dependent pattern. Lactobacillus acidophilus ATCC 43121 as a control showed high cholesterol removal by growing cells, whereas resting and dead cells showed less cholesterol removal. Scanning electron micrographs showed that large amounts of cholesterol adhered to surfaces of growing and dead cells of L. plantarum EM without changes in cell morphology. On the other hand, only a small amount of cholesterol adhered to the surface of L. acidophilus ATCC 43121 cells, and growing cells of L. acidophilus ATCC 43121 showed morphological changes with a thinner and longer shape. Based on these results, cholesterol removal mechanisms by L. plantarum EM could be attributed to enzymatic assimilation including bile salt hydrolase activity and cell surface-binding. Further, L. plantarum EM showed reasonable tolerance to acid and bile stresses and displayed antagonistic activity against pathogens. Moreover, L. plantarum EM did not represent a health risk due to antibiotic resistance. The results of this study indicate that L. plantarum EM may be a promising probiotic candidate and adjunct culture for reduction of serum cholesterol level regardless of its viability.

Lower Squalene Epoxidase and Higher Scavenger Receptor Class B Type 1 Protein Levels Are Involved in Reduced Serum Cholesterol Levels in Stroke-Prone Spontaneously Hypertensive Rats.

A lower serum cholesterol level was recently shown to be one of the causes of stroke in an epidemiological study. Spontaneously hypertensive rats stroke-prone (SHRSP) have lower serum cholesterol levels than normotensive Wistar-Kyoto rats (WKY). To elucidate the mechanisms responsible for the lower serum cholesterol levels in SHRSP, we determined whether the amounts of cholesterol biosynthetic enzymes or the receptor and transporter involved in cholesterol uptake and efflux in the liver were altered in SHRSP. When the mRNA levels of seven cholesterol biosynthetic enzymes were measured using real-time polymerase chain reaction (PCR), farnesyl pyrophosphate synthase and squalene epoxidase (SQE) levels in the liver of SHRSP were significantly lower than those in WKY. SQE protein levels were significantly reduced in tissues other than the brain of SHRSP. No significant differences were observed in low-density lipoprotein (LDL) receptor (uptake of serum LDL-cholesterol) or ATP-binding cassette transporter A1 (efflux of cholesterol from the liver/formation of high-density lipoprotein (HDL)) protein levels in the liver and testis between SHRSP and WKY, whereas scavenger receptor class B type 1 (SRB1: uptake of serum HDL-cholesterol) protein levels were higher in the livers of SHRSP. These results indicated that the lower protein levels of SQE and higher protein levels of SRB1 in the liver were involved in the reduced serum cholesterol levels in SHRSP.