High Blood Cholesterol Levels Research Articles

Therapeutic potential of stem cells from human exfoliated deciduous teeth infusion into patients with type 2 diabetes depends on basal lipid levels and islet function.

Mesenchymal stem cells (MSCs) hold great potential in treating patients with diabetes, but the therapeutic effects are not always achieved. Particularly, the clinical factors regulating MSC therapy in this setting are largely unknown. In this study, 24 patients with type 2 diabetes mellitus (T2DM) treated with insulin were selected to receive three intravenous infusions of stem cells from human exfoliated deciduous teeth (SHED) over the course of 6 weeks and were followed up for 12 months. We observed a significant reduction of glycosylated serum albumin level (P < .05) and glycosylated hemoglobin level (P < .05) after SHED transplantation. The total effective rate was 86.36% and 68.18%, respectively, at the end of treatment and follow‐up periods. Three patients ceased insulin injections after SHED transplantation. A steamed bread meal test showed that the serum levels of postprandial C‐peptide at 2 hours were significantly higher than those at the baseline (P < .05). Further analysis showed that patients with a high level of blood cholesterol and a low baseline level of C‐peptide had poor response to SHED transplantation. Some patients experienced a transient fever (11.11%), fatigue (4.17%), or rash (1.39%) after SHED transplantation, which were easily resolved. In summary, SHED infusion is a safe and effective therapy to improve glucose metabolism and islet function in patients with T2DM. Blood lipid levels and baseline islet function may serve as key factors contributing to the therapeutic outcome of MSC transplantation in patients with T2DM.

Characterization of polycystic ovary syndrome among Flo app users around the world

BackgroundPolycystic ovary syndrome (PCOS) is a complex and multi-faceted endocrine disorder that affects 5–20% of women. Literature is limited regarding potentially differing PCOS phenotypes among women around the world.ObjectiveTo use Flo app technology to understand the multifaceted characteristics of PCOS across several countries and identify contributing risk factors to the development of this condition.Study designFlo is a widely used female health and wellbeing app with period tracking functionality that provides a globally representative and medically unbiased perspective on PCOS symptomatology. A chatbot dialog on PCOS was subsequently administered on the Flo application (app) to users from 142 countries (with at least 100 respondents) who have the app running in English during September–October 2019.ResultsFor analyses, we selected the five countries with the greatest number of respondents: US (n = 243,238), UK (n = 68,325), India (n = 40,092), Philippines (n = 35,131), and Australia (n = 29,926). Bloating was the most frequently reported symptom among PCOS-positive women and appeared to be the main predictor of PCOS in our model (odds ratio 3·76 [95% CI 3·60–3·94]; p < 0·0001). Additional top predictors of PCOS are high blood cholesterol and glucose levels. As BMI increased, the percentage of women who reported a physician-confirmed PCOS diagnosis also increased. However, women in India did not follow this trend.ConclusionOur findings are based on the largest known PCOS dataset and indicate that symptoms are more complex than previously understood. The most frequently reported symptoms (bloating, facial hirsutism, irregular cycles, hyperpigmentation, and baldness) are broader than those included in the Rotterdam criteria. Future work should reevaluate and refine the criteria utilized in PCOS diagnosis.

Influence of Habitual Dairy Food Intake on LDL Cholesterol in a Population-Based Cohort.

Background: Cholesterol has a pivotal role in human physiology, exerting both structural and functional activity. However, higher blood cholesterol levels, especially low-density lipoprotein cholesterol (LDL-C), are a major cardiovascular risk factor. Therefore, special attention has been given to the effect of dietary factors in influencing LDL-C blood levels. In particular, much research has focused on dairy products, since they are a main component of different dietary patterns worldwide. A large body of evidence did not support the hypothesis that dairy products significantly increase circulating LDL-C, but no definitive data are available. Hence, we aimed to assess the relationships among LDL-C, habitual dairy food intake and anthropometric variables in a cohort representative of the general population in a Mediterranean area. Methods: We evaluated 802 healthy adults included in the ABCD_2 (Alimentazione, Benessere Cardiovascolare e Diabete) study (ISRCTN15840340), a longitudinal observational single-center study of a cohort representative of the general population of Palermo, Sicily. The habitual intake of dairy products was assessed with a validated food frequency questionnaire, and LDL-C serum levels and several anthropometric parameters were measured. Results: The group with high LDL-C serum concentrations (≥130 vs. <130 mg/dL) exhibited higher age, body mass index (BMI), waist-to-hip ratio (WHR), body fat percentage, systolic and diastolic blood pressure, carotid intima-media thickness and glycated hemoglobin. The habitual diet was not different between the groups in terms of macronutrient, cholesterol, egg and dairy food intake, with the exception of the weekly number of portions of milk (higher in the low LDL-C group vs. the high LDL-C group) and ricotta cheese (higher in the high LDL-C group vs. the LDL-C group). No significant correlation was found between LDL-C blood levels and the habitual intake of dairy products or the dietary intake of cholesterol and fats. The multivariate regression analyses (R2 = 0.94) showed that LDL-C blood levels were significantly associated with the habitual intake of milk (p < 0.005) and ricotta cheese (p < 0.001) and with BMI (p < 0.001). Conclusion: Our study reported that total dairy food consumption was not correlated with LDL-C blood levels. However, multivariate analyses showed an inverse association between serum LDL-C and milk intake as well as a positive association between ricotta cheese intake and LDL-C concentrations. More studies are needed to better characterize the relationship between dairy products and circulating LDL-C.

OMEGA 3 SUPPLEMENTATION DECREASE A BLOOD CHOLESTROL LEVEL IN TRAINED WOMEN

AbstractBackground : Trained woean who experiencing menstrual disoders are found with high blood cholesterol level. This situation is contrary to who don’t experience menstrual disorder. Mentrual disorder condition has a low estrogen level. The low estrogen level is associated with endothelial disfunction which causes blood cholesterol increase. The benefit of omega 3 supplementation have been clinically proven to prevent atherosclerosis, decrease blood cholesterol levels, and playong an important role in modulating inflamation. Omega 3 supplementation is expected to decrease blood cholesterol levels in trained women. Method: This research is using field experimental with case control method. The samples are 30 trained womens contained by 15 are controlled and 15 are given treatment. The sampling technique is randomized allocation. The independent variabel is omega 3 300mg supplementation and the dependent variabel is blood cholesterol levels. Data are analized using parametric statistic paired T-test. Result: The bivariate analysis showed there is a meaningful difference on blood cholesterol levels in the treatment group p=0,0027 and no change in control group p=0,191 during treatment for 8 weeks. Conclusion: Omega 3 supplementation decrease a blood cholesterol levels in trained women.

Brown Algae Potential as a Functional Food against Hypercholesterolemia: Review.

Brown algae have been part of the human diet for hundreds of years, however, in recent years, commercial and scientific interest in brown algae has increased due to the growing demand for healthier diet by the world population. Brown algae and its metabolites, such as carotenoids, polysaccharides, phlorotannins, and proteins, have been associated with multiple beneficial health effects for different diseases, such as cardiovascular diseases, one of the main causes of death in Europe. Since high blood cholesterol levels are one of the major cardiovascular risks, this review intends to provide an overview of current knowledge about the anti-hypercholesterolemic effect of different brown algae species and/or their isolated compounds.

The frequency of dyslipidemia in patients with idiopathic tinnitus.

OBJECTIVEWe aimed to investigate the presence of dyslipidemia in blood biochemistry of patients with idiopathic tinnitus and to point out that dyslipidemia poses a risk to coronary artery disease.METHODSBlood lipoprotein values and age and gender were compared between 158 patients with idiopathic tinnitus and 160 patients without tinnitus. Results were statistically evaluated.RESULTSIn total, more than half of 318 patients had high blood cholesterol levels. In both groups, the cholesterol average was 215 mg/dl. Furthermore, low density lipoprotein (LDL) and high density lipoprotein (HDL) levels were higher than normal. However, no statistically significant difference was determined in the comparison of Cholesterol, HDL, and LDL levels in both groups (p<0.05). However, serum triglyceride levels of patients with tinnitus were when compared with the control group, a statistically significant difference was found (p=0.001); The numbers of men and women were approximately close to each other and the number of patients between the ages of 50 and 60 was higher. The average age is 53. As a result, the risk of life-threatening coronary heart disease increases, as the majority of patients with tinnitus are in the middle age group and have high lipoprotein values.CONCLUSIONIn patients presenting with the complaint of tinnitus, high serum lipoprotein values may not be directly related to tinnitus. However, it should be remembered that the presence of dyslipidemia may affect coronary vessels and lead to coronary artery diseases. However, a significant correlation was found between high serum triglyceride levels and tinnitus. In addition, if the patient has dyslipidemia, it will be healthy to treat dyslipidemia.

EFFECTS OF PURE AND FAKE HONEY ON GLUCOSE AND LIPID PROFILE in vitro AND in vivo STUDY

Honey authenticity is one of the most critical honey trading issues worldwide. Fake honey (FH) represents almost 80% of the honey market in Malaysia. Apart from violating consumer’s rights, FH consists of none of the beneficial nutritional value other than pure honey (PH). Moreover, prolonged consumption of FH may cause harm to human health. However, data regarding these issues is limited. In this study, both PH and FH were tested using 3T3-L1 adipocytes and in high-fat diet (HFD)-induced obese Sprague Dawley rats. Initially, a physicochemical analysis was performed on both the honey samples according to the Codex Alimentarius Commission and International Honey Commission procedures. After 72 hr, PH significantly reduced lipid accumulation and triglyceride levels in the adipocytes. In the rats, low glucose, cholesterol, and triglyceride levels were significantly detected after orally administered for 16 weeks. Conversely, FH significantly induced higher lipid accumulation and triglyceride levels in adipocytes and excess high blood glucose, cholesterol, and triglyceride levels in rats. The results demonstrated that FH has negative effects on lipid metabolism, and prolonged consumption may cause health complications. Furthermore, prompt actions are required to address this problem.

A new activator of esterase D decreases blood cholesterol level through ESD/JAB1/ABCA1 pathway.

Excessively high cholesterol content in the blood leads to nonalcoholfatty liver disease (NAFLD) and arteriosclerosis. Although there are increasing publications and patent applications to lower blood cholesterol with small chemical molecules, limited effective drugs can be available in clinic. It is necessary to uncover new targets and drugs to alleviate high cholesterol. Esterase D (ESD) is abundant in liver and it remains unknown about its role in cholesterol metabolism. Here we reported that small chemical molecule fluorescigenic pyrazoline derivative 5 (FPD5), a new ESDactivator, could effectively reverse high blood cholesterol level and prevent fatty liver and arteriosclerosis in apoE-/- mice fed the high-fat diet. We also observed that FPD5 could reduce oxidized low density lipoprotein (oxLDL)-induced formation of foam cells. To further investigate the mechanism of FPD5 action on blood cholesterol modulation, we found that ESD trigged by FPD5 was aggregated in lysosome and interacted with Jun activation domain binding protein 1 (JAB1). ESD served as a deacetylase to remove Thr89 acetylation of JAB1 and increased its activity; thus,promoting the ATP-binding cassette transporters A1 (ABCA1) to accelerate cholesterol efflux. Our findings demonstrate that FPD5 decreases blood cholesterol level to ameliorate NAFLD and arteriosclerosis through ESD/JAB1/ABCA1 pathway, and ESD functions as a novel nonclassical deacetylase that hydrolyzes serine/threonine acetyl group. Our findings not only highlight that FPD5 may be a pioneer drug for alleviating blood cholesterolbut also indicate that ESD is a potential drug target that promotes cholesterol metabolism.

Guggulu and Triphala for the Treatment of Hypercholesterolaemia: A Placebo-Controlled, Double-Blind, Randomised Trial

Background: Several herbs are used for lowering high blood cholesterol levels in traditional medicines including Indian Medicine (Ayurveda). We aimed to assess the short-term effects of the combination of Guggulu (Commiphora mukul) and Triphala (Terminalia chebula, Terminalia belerica, and Phyllanthus emblica) on serum cholesterol in healthy subjects with hypercholesterolaemia. Patients and Methods: This was a parallel randomised double-blind controlled trial that included 90 individuals at low-moderate cardiovascular risk. The main outcome measures were serum levels of total and low- and high-density lipoprotein cholesterol (LDL-C, HDL-C). Secondary outcome measures included BMI, waist circumference, and adverse events. Subjects were administered either Guggulu and Triphala or placebo three times daily for 3 months, with 3 months of follow-up after the end of treatment. Results: At intention-to-treat analysis, from baseline to 3 months, total serum cholesterol decreased by 1.9% in the placebo (n = 44) and 3.3% (p = 0.01) in the intervention (n = 46) group. Serum LDL-C decreased by 4.9% (p = 0.03) and 4.8% (p = 0.02) in the placebo and intervention group, respectively, without differences between them. Two participants in the intervention group developed hypersensitivity rash (4.3%) as compared with none in the placebo group. Conclusions: Three months of treatment with Guggulu and Triphala did not show better effects than placebo on serum levels of total and LDL cholesterol, BMI, and waist circumference.

Prevalence and risk factors for overweight and obesity: a cross-sectional countrywide study in Burkina Faso

ObjectiveThe objective of this study was to determine the prevalence and predictors of overweight and obesity in Burkina Faso using a population-based countrywide sample. We hypothesise that there is a...

Role of the Fatty Acid Binding Proteins in Cardiovascular Diseases: A Systematic Review.

Cardiovascular diseases (CVD) remain a global pandemic and leading cause of deaths worldwide. While several guidelines have been developed to control the development of CVDs, its prevalence keeps on increasing until this day. Cardiovascular risk factors, such as reduced exercises and high fat or glucose diets, culminate in the development of the metabolic syndrome and eventually atherosclerosis, which is driven by high blood lipid and cholesterol levels, and by endothelial dysfunction. Late complications of atherosclerosis give rise to serious clinical cardiovascular manifestations such as myocardial infarction and hypertension. Therefore, endothelial functions and the lipid metabolism play critical roles in the pathogenesis of CVDs. Fatty acid-binding proteins are a family of intracellular proteins expressed in many cell types known mainly for their interaction with and trafficking of cellular lipids. The roles of a number of isoforms in this family have been implicated in lipid metabolic homeostasis, but their influence on endothelial function and vascular homeostasis remain largely unknown. This review’s purpose is to update fundamentals about the connection between cardiovascular disease, metabolism, endothelial function, and mainly the roles of fatty acid-binding proteins.

Cholesterol Homeostasis: An In Silico Investigation into How Aging Disrupts Its Key Hepatic Regulatory Mechanisms.

Simple SummaryCardiovascular disease is the leading cause of death worldwide. High blood cholesterol levels are associated with an increased risk of this condition. How high levels of blood cholesterol result in cardiovascular disease during aging is a difficult question to answer. Computational models have been used over the years to help understand this problem, as they are capable of representing complex systems such as this. The aim of this work was to use a computational model of cholesterol metabolism to better understand why, in certain studies involving the oldest old (persons ≥ 85 years), high blood cholesterol levels have been associated with a decreased risk of death. Using our computational model, we found that key age-associated changes to how cholesterol is processed in the liver could be responsible for this observation. The findings from our work contribute to our understanding of cholesterol metabolism in older people and how treatments could be developed in the future to promote healthy aging.The dysregulation of intracellular cholesterol homeostasis is associated with several age-related diseases, most notably cardiovascular disease (CVD). Research in this area has benefitted from using computational modelling to study the inherent complexity associated with the regulation of this system. In addition to facilitating hypothesis exploration, the utility of modelling lies in its ability to represent an array of rate limiting enzymatic reactions, together with multiple feedback loops, which collectively define the dynamics of cholesterol homeostasis. However, to date no model has specifically investigated the effects aging has on this system. This work addresses this shortcoming by explicitly focusing on the impact of aging on hepatic intracellular cholesterol homeostasis. The model was used to investigate the experimental findings that reactive oxygen species induce the total activation of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase (HMGCR). Moreover, the model explored the impact of an age-related decrease in hepatic acetyl-CoA acetyltransferase 2 (ACAT2). The model suggested that an increase in the activity of HMGCR does not have as significant an impact on cholesterol homeostasis as a decrease in hepatic ACAT2 activity. According to the model, a decrease in the activity of hepatic ACAT2 raises free cholesterol (FC) and decreases low-density lipoprotein cholesterol (LDL-C) levels. Increased acetyl CoA synthesis resulted in a reduction in the number of hepatic low-density lipoprotein receptors, and increased LDL-C, FC, and cholesterol esters. The rise in LDL-C was restricted by elevated hepatic FC accumulation. Taken together these findings have important implications for healthspan. This is because emerging clinical data suggest hepatic FC accumulation is relevant to the pathogenesis of non-alcoholic fatty liver disease (NAFLD), which is associated with an increased risk of CVD. These pathophysiological changes could, in part, help to explain the phenomenon of increased mortality associated with low levels of LDL-C which have been observed in certain studies involving the oldest old (≥85 years).

PCSK9 and LRP5 in macrophage lipid internalization and inflammation

Atherosclerosis, the leading cause of cardiovascular diseases, is driven by high blood cholesterol levels and chronic inflammation. Low-density lipoprotein receptors (LDLR) play a critical role in regulating blood cholesterol levels by binding to and clearing LDLs from the circulation. The disruption of the interaction between proprotein convertase subtilisin/kexin 9 (PCSK9) and LDLR reduces blood cholesterol levels. It is not well known whether other members of the LDLR superfamily may be targets of PCSK9. The aim of this work was to determine if LDLR-related protein 5 (LRP5) is a PCSK9 target and to study the role of PCSK9 and LRP5 in foam cell formation and lipid accumulation. Primary cultures of human inflammatory cells (monocytes and macrophages) were silenced for LRP5 or PCSK9 and challenged with LDLs. We first show that LRP5 is needed for macrophage lipid uptake since LRP5-silenced macrophages show less intracellular CE accumulation. In macrophages, internalization of LRP5-bound LDL is already highly evident after 5 h of LDL incubation and lasts up to 24 h; however, in the absence of both LRP5 and PCSK9, there is a strong reduction of CE accumulation indicating a role for both proteins in lipid uptake. Immunoprecipitation experiments show that LRP5 forms a complex with PCSK9 in lipid-loaded macrophages. Finally, PCSK9 participates in TLR4/NFkB signalling; a decreased TLR4 protein expression levels and a decreased nuclear translocation of NFκB were detected in PCSK9 silenced cells after lipid loading, indicating a downregulation of the TLR4/NFκB pathway. Our results show that both LRP5 and PCSK9 participate in lipid uptake in macrophages. In the absence of LRP5, there is a reduced release of PCSK9 indicating that LRP5 also participates in the mechanism of release of soluble PCSK9. Furthermore, PCSK9 up-regulates TLR4/NFκB favouring inflammation.

The Analysis of Changes in Food Preferences and Nutrition-Related Diseases (Conditions) in the Population of the Russian Federation

Introduction: Many countries develop approaches to understanding nutritional balance in order to estimate adequate intakes for each type of food and nutrient required to preserve health of individuals and the population as a whole. The objective of the study was to analyze changes in food preferences and diet-related diseases (conditions) in the population of the Russian Federation over a five-year period. Methods: A retrospective comparative analysis of data of questionnaire-based surveys of the population of the Russian Federation conducted in 2013 and 5 years later in 2018 by the Federal State Statistics Service in accordance with Decree No. 946 of the Russian Government of November 27, 2010 was conducted. Results: Both positive and negative changes were observed in the diet and health status of Russian people over the study period. The positive ones included an increase in the number of people consuming healthy foods on a daily basis and rejecting products with low biological value, especially in big cities, and a decrease in the number of people with diabetes or hyperglycemia. The observed negative changes included an increase in the proportion of people with excessive dietary fat intake, insufficient consumption of complex carbohydrates, and nutrition-related high blood cholesterol levels.

Cytotoxicity and Antimicrobial Activity of Chromium Picolinate Mediated Zinc Oxide Nanoparticle

Aim: To study the chromium picolinate mediated with zinc oxide nanoparticle and its cytotoxicity and antimicrobial activity&#x0D; Introduction: Chromium can alleviate glucose intolerance and insulin resistance and it is involved in the metabolism of glucose, lipid, protein, and nucleic acid .Chromium picolinate [CrPic], also named as picolinic acid chromium and several studies have proved that CrPic, as the source of Chromium, can alleviate the high level of blood glucose, blood lipid, insulin, and cholesterol in the patients with metabolic syndrome and zinc oxide [ZnO] has also gained momentum due to their unique properties in the process of nanotechnology. Chromium picolinate works together with insulin that produced by the pancreas to metabolize carbohydrates. It's made by combining chromium with picolinic acid. The acid helps the body absorb chromium. Randomized controlled trials have failed to demonstrate a link between chromium supplementation and the prevention or treatment of type 2 diabetes or impaired glucose tolerance. Chromium supplementation of young men and women does not promote muscle accretion, fat loss, or gains in strength. Physically active individuals with concerns about meeting guidelines for nutrient intake should be counseled to select and consume foods with high nutrient densities rather than to rely on nutritional supplements.&#x0D; Materials and Methods: Chromium picolinate mediated with ZnO nanoparticles were evaluated for its antibacterial activity and cytotoxicity potential using brine shrimp lethality assay.&#x0D; Results: Chromium picolinate mediated zinc oxide nanoparticles show good results in antimicrobial activity as well as in cytotoxicity.&#x0D; Conclusion: Chromium picolinate mediated Zn nanoparticles is an efficient antibacterial and a potential cytotoxicity agent.

Molecular investigation of modified β-cyclodextrin and cholesterol inclusion complexes through molecular docking simulations

Hypertension, a medical condition which commonly associated with cardiovascular diseases, the most lethal non-communicable diseases in the world, is indicated by the high blood cholesterol level. Thus, maintaining the blood cholesterol level is essential especially for hypertension-diagnosed patients. In this study, the molecular docking simulations were successfully performed between cholesterol and methylene blue (MB) with the modified β-cyclodextrin (BCD) compounds as the guest and host molecules, respectively, to investigate their molecular interaction when forming the inclusion complexes. The docking results showed that the modification on the -OH hydroxyl group at position 6 of BCD improves the binding affinity of the cholesterol when forming the inclusion complex, where the -OCH3 modification has the highest binding affinity toward cholesterol, with ΔGbinding value of -5.9 kcal/mol, followed by -OCH2CHO, -OCH2COOH and -OCOCOH(COOH)2, with ΔGbinding value of -5.8 kcal/mol. Moreover, the hydrophobic and van der Waals interactions were observed as the most dominant interactions when both BCD-modified compounds/cholesterol and BCD-modified compounds/MB inclusion complexes were formed. Thus, the electrochemical technique can be employed toward the cholesterol and these BCD-modified compounds to validate the docking results and determine its sensitivity as cholesterol sensor.

The Effect Of Giving Green Tea To Elderly With Hypertension Disease To Decrease The Level Of Cholesterol At Tamban Baru Health Center

Background: High blood cholesterol levels lead to cholesterol deposits in blood vessels walls, the more sediment will clog blood vessels and disrupt blood circulation. This condition is the trigger of heart disease and stroke. To overcome the problems of high cholesterol in the blood, now it has begun to use natural ingredients to lower blood cholesterol levels that are the treatment by using herbal medicines such as medicines such as medicinal plants one of them is green tea. The main purpose the study is to know the effect of green tea on cholesterol values in elderly hypertensive patients in at Tamban baru community health centre in Tamban Baru Mekar Village. Methods: the research design used for this research is pre experimental one group, pretest and posttest design. The subject is elderly people with high cholesterol hypertension. Sampling technique in this research is purposive sampling technique with numbers of respondents 16 respondents who were given treatment. The research instrument used in this research is independent variable green tea giving and the dependent variable is cholesterol measures on elderly hypertensive patient using rapid test tool of cholesterol stick multi check in three, bivariate analysis using paired T test. Respondents were given green tea twice a day every morning and afternoon for 14 days

Exploring the Bacterial Impact on Cholesterol Cycle: A Numerical Study.

High blood cholesterol levels are often associated with cardiovascular diseases. Therapeutic strategies, targeting different functions involved in cholesterol transport or synthesis, were developed to control cholesterolemia in human. However, the gut microbiota is also involved in cholesterol regulation by direct biotransformation of luminal cholesterol or conversion of bile salts, opening the way to the design of new strategies to manage cholesterol level. In this report, we developed for the first time a whole-body human model of cholesterol metabolism including the gut microbiota in order to investigate the relative impact of host and microbial pathways. We first used an animal model to investigate the ingested cholesterol distribution in vivo. Then, using in vitro bacterial growth experiments and metabolite measurements, we modeled the population dynamics of bacterial strains in the presence of cholesterol or bile salts, together with their bioconversion function. Next, after correct rescaling to mimic the activity of a complex microbiota, we developed a whole body model of cholesterol metabolism integrating host and microbiota mechanisms. This global model was validated with the animal experiments. Finally, the model was numerically explored to give a further insight into the different flux involved in cholesterol turn-over. According to this model, bacterial pathways appear as an important driver of cholesterol regulation, reinforcing the need for development of novel “bacteria-based” strategies for cholesterol management.

Hypercholesterolemia Interferes with Induction of miR-125b-1-3p in Preconditioned Hearts.

Ischemic preconditioning (IPre) reduces ischemia/reperfusion (I/R) injury in the heart. The non-coding microRNA miR-125b-1-3p has been demonstrated to play a role in the mechanism of IPre. Hypercholesterolemia is known to attenuate the cardioprotective effect of preconditioning; nevertheless, the exact underlying mechanisms are not clear. Here we investigated, whether hypercholesterolemia influences the induction of miR-125b-1-3p by IPre. Male Wistar rats were fed with a rodent chow supplemented with 2% cholesterol and 0.25% sodium-cholate hydrate for 8 weeks to induce high blood cholesterol levels. The hearts of normo- and hypercholesterolemic animals were then isolated and perfused according to Langendorff, and were subjected to 35 min global ischemia and 120 min reperfusion with or without IPre (3 × 5 min I/R cycles applied before index ischemia). IPre significantly reduced infarct size in the hearts of normocholesterolemic rats; however, IPre was ineffective in the hearts of hypercholesterolemic animals. Similarly, miR-125b-1-3p was upregulated by IPre in hearts of normocholesterolemic rats, while in the hearts of hypercholesterolemic animals IPre failed to increase miR-125b-1-3p significantly. Phosphorylation of cardiac Akt, ERK, and STAT3 was not significantly different in any of the groups at the end of reperfusion. Based on these results we propose here that hypercholesterolemia attenuates the upregulation of miR-125b-1-3p by IPre, which seems to be associated with the loss of cardioprotection.

SAT-LB95 Low Density Lipoprotein Receptor and Proprotein Convertase Subtilisin/Kexin Type 9 Kinetics Using Heavy Water (2H2O) Labeling and Mass Spectrometry

Abnormally high blood cholesterol levels in low density lipoprotein (LDL) increases the risk of heart disease. Cell surface receptors such as LDL-receptors (LDLr) regulate the clearance of LDL from blood circulation. As cholesterol levels decrease, cells promote cholesterol synthesis and cholesterol uptake by increasing LDLr expression. Another regulatory protein of plasma cholesterol clearance is proprotein convertase subtilisin/kexin type 9 (PCSK9). It is secreted from the liver into circulation where it can bind to and target LDLr to the lysosome for subsequent degradation. The current model of cholesterol regulation describes how increased cholesterol content down-regulates the number of LDLr promoted by PCSK9 mediated degradation, however minimal knowledge is not known about LDLr and PCSK9 kinetics using heavy water labeling, and how cholesterol enriched diet affects LDLr and PCSK9 kinetics in vivo. Therefore, our objective(s) were to establish a method 1) to measure the kinetics of LDLr and PCSK9 via stable isotopic metabolic labeling with heavy water (2H2O) in vivo 2) to further test established models of cholesterol metabolic regulation on LDLr and PCSK9 turnover after feeding mice a cholesterol enriched diet. We hypothesize that a cholesterol enriched diet will decrease both LDLr and PCSK9 synthesis rates. In order to test this, mice were fed a cholesterol enrich diet for 1 week and metabolically labeled with heavy water (2H2O) up to 36 hours. LDLr and PCSK9 were immunoprecipitated from liver and deuterium incorporation into LDLr and PCSK9 were measured via mass spectrometry. Our results revealed high cholesterol feeding down-regulated cholesterol synthesis and LDLr fractional synthesis rate decreased from 10.0% to 6% per hour. PCSK9 concentration also decreased from 1 to 0.2 (ng/ml / total mg protein), but the synthesis rate increased from 9.0%/day in control mice to 19.5%/day in high cholesterol diet. These results suggest high cholesterol feeding increases PCSK9 synthesis that potentially depletes the intracellular pool to target LDLr to the lysosome thus decreasing LDLr turnover. This research provides a flux-based approach to measure the kinetics of LDLr and PCSK9 for a molecular based kinetic insight of their functions in physiology, disease and therapy.