Elevated Serum Cholesterol Levels Research Articles

Surgical removal of multiple xanthomas in familial hypercholesterolemia: a case report

Introduction: Xanthomas are skin swellings that are caused by the accumulation of cholesterol and lipids in the body. They are associated with lipid disorders, such as familial hypercholesterolemia (FH). FH is a rare genetic disorder which is characterized mainly by high levels of LDL cholesterol. Case presentation: We report a case of an 11-year-old female who had multiple swellings all over the body with the largest measuring 7×4×3 cm in diameter. These lesions were gradually increasing in size since 4 years. She was being bullied by her school colleagues because of swellings appearance. Clinical examination revealed multiple yellowish masses on the patient’s elbows, knees, and buttocks which were painless, firm, and non-tender. Laboratory tests revealed elevated levels of serum cholesterol (512 mg/dL) and LDL cholesterol (469.2 mg/dL). Masses Ultrasound showed similar echogenicity to upper and lower extremities subcutaneous fat. Incisional biopsy microscopic images revealed clusters of foam cells. These findings led to a diagnosis of Homozygous FH (HoFH) and she underwent surgery to remove the xanthomas on her elbows. Discussion: Xanthomas are small, yellowish skin swellings that form due to the presence of high lipids. As they are typically painless and small, this could lead to a late treatment or misdiagnosis. Drugs, life style changes and surgery represent treatment plan options. Conclusion: Xanthomas can be the first indication of an underlying hypercholesterolemia problem and this case report highlights the importance of early diagnosis of HoFH by providing the suitable management for this case in its early stages which can prevent developing serious complication.

High-iron consumption decreases copper accumulation and colon length, and alters serum lipids

In this study, we aimed to demonstrate that a significant increase in dietary iron intake disrupts the regulation of copper availability, ultimately leading to systemic copper deficiency. To investigate this, we conducted experiments using five-week-old male weanling Sprague–Dawley rats fed diets based on AIN-93G with some modifications. These diets featured varying iron content, offering choices of adequate iron (~ 120 μg/g, near the upper limit [UL]) or high iron (~ 7544 μg/g), along with low (~ 0.3 μg/g), adequate (~ 6 μg/g), or high (~ 153 μg/g) levels of dietary copper over a 5-week period. Rats consuming the high-iron diets displayed anemia, reduced copper levels in their organs and feces, and shortened colon lengths. Increased dietary iron intake resulted in an overall reduction in copper distribution within the body, likely leading to severe copper deficiency-related disorders in the experimental rats. However, the physiological disturbances caused by a high-iron diet were prevented when additional copper was included in the rodent diet. Furthermore, high iron intake led to copper deprivation, and high iron consumption resulted in elevated serum cholesterol levels. However, increasing dietary copper consumption led to a decrease in overall serum cholesterol levels. Additionally, serum alkaline phosphate and aspartate aminotransferase levels were increased by high-iron feeding, regardless of dietary copper concentration, while alanine aminotransferase levels decreased.

Investigating the relationship between intracranial atherosclerotic plaque remodelling and diabetes using high-resolution vessel wall imaging.

Intracranial atherosclerosis, a leading cause of stroke, involves arterial plaque formation. This study explores the link between plaque remodelling patterns and diabetes using high-resolution vessel wall imaging (HR-VWI). To investigate the factors of intracranial atherosclerotic remodelling patterns and the relationship between intracranial atherosclerotic remodelling and diabetes mellitus using HR-VWI. Ninety-four patients diagnosed with middle cerebral artery or basilar artery atherosclerosis were enrolled. Their basic clinical data were collected, and HR-VWI was performed. The vascular area at the plaque (VAMLN) and normal reference vessel (VAreference) were delineated and measured using image postprocessing software, and the Remodelling index (RI) was calculated. According to the value of the RI, the patients were divided into a positive remodelling (PR) group, intermediate remodelling (IR) group, negative remodelling (NR) group, PR group and non-PR (N-PR) group. The PR group exhibited a higher prevalence of diabetes and serum cholesterol levels than the IR and NR groups [45.2%, 4.54 (4.16, 5.93) vs 25%, 4.80 ± 1.22 and 16.4%, 4.14 (3.53, 4.75), respectively, P < 0.05]. The diabetes incidence was also significantly greater in the PR group than in the N-PR group (45.2% vs 17.5%, P < 0.05). Furthermore, the PR group displayed elevated serum triglyceride and cholesterol levels compared to the N-PR group [1.64 (1.23, 2.33) and 4.54 (4.16, 5.93) vs 4.54 (4.16, 5.93) and 4.24 (3.53, 4.89), P < 0.05]. Logistic regression analysis revealed diabetes mellitus as an independent influencing factor in plaque-PR [odds ratio (95% confidence interval): 3.718 (1.207-11.454), P < 0.05]. HR-VWI can clearly show the morphology and signal characteristics of intracranial vascular walls and plaques. Intracranial atherosclerotic plaques in diabetic patients are more likely to show PR, suggesting poor plaque stability and a greater risk of stroke.

Effect of Chronic Hepatitis B Virus (HBV) Infection on Lipid Profile in Iraqi Patients

Hepatitis B Virus (HBV) is known to target the liver, potentially leading to liver diseases. There's a notable link between dyslipidemia, an anomaly in lipid levels, and HBV infection. This research seeks to delve into the relationship between abnormal lipid profiles and HBV infection. The current study analyzed 90 participants; 50 of whom were patients with chronic HBV infection, and the remaining 40 were healthy individuals serving as the control group. Each participant took part in interviews and contributed blood samples for the analysis of their lipid profiles. The Cobas C 311 Roche System was employed to measure levels of HDL, cholesterol, LDL, triglyceride, and VLDL cholesterol, adhering to established lab protocols. The results showed that the HBV patient group had significantly elevated serum cholesterol, LDL, and triglyceride levels when compared to the healthy controls. Conversely, the HDL levels in the patient group were notably lower. Serum VLDL levels did not show any significant variation between the groups. The study identified altered lipid profiles in HBV patients, suggesting increased dyslipidemia and cardiovascular risks. Additional investigation is required to identify the root causes and suggest appropriate solutions.

Low-dose atorvastatin protects skeletal muscle mitochondria in high-fat diet-fed mice with mitochondrial autophagy inhibition and fusion enhancement

Despite the great clinical benefits of statins in cardiovascular diseases, their widespread use may lead to adverse muscle reactions associated with mitochondrial dysfunction. Some studies have demonstrated that statins provide substantial improvement to skeletal muscle health in mice. Our previous study found that oral treatment with atorvastatin (Ator, 3 mg/kg) protected myocardial mitochondria in high-fat diet (HFD)-fed mice. Therefore, this study aimed to explore the influence of low-dose Ator (3 mg/kg) on mitochondria in skeletal muscle under cholesterol overload. Male C57BL/6J mice were fed a HFD for 18 weeks and orally administered Ator (3 mg/kg) during the last 12 weeks. Ator treatment had no effects on elevated serum cholesterol and glucose levels in HFD-fed mice. Serum creatine kinase levels and the cross-sectional area of muscle cells were not affected by HFD feeding or Ator treatment. Increased expression of PINK1-LC3 II (activated mitophagy), MFN2 (fusion), and PGC-1α (biogenesis) proteins was induced in the skeletal muscles of HFD-fed mice. Treatment with Ator inhibited PINK1 and LC3 II protein expression, but further promoted MFN1, MFN2, and OPA1 expression. The impairments in mitochondrial quality and morphology in HFD-fed mice were attenuated by treatment with Ator. Furthermore, Ator treatment enhanced glucose oxidation capacity and restored ATP production in the skeletal muscles of HFD-fed mice. The study reveals that low-dose Ator has a protective effect on muscle mitochondria in mice, likely through inhibiting mitophagy and enhancing mitochondrial fusion. This suggests that skeletal muscle mitochondria may be one of low-dose Ator-mediated protective targets.

The effect of HLA-DRB1*04:01 on a mouse model of atherosclerosis

ObjectivesHLA-DRB1 is associated with an increased risk of cardiovascular disease in patients with rheumatoid arthritis (RA). This study aimed to determine the effect of HLA-DRB1 on atherosclerotic cardiovascular disease (ASCVD) using a novel mouse model. MethodsMice transgenic for HLA-DRB1*04:01 (DR4tg) were crossed with low density lipoprotein receptor knock-out (Ldlr−/−) mice that develop atherosclerosis when fed a high fat, high cholesterol (HFHC) diet. Male and female DR4tgLdlr−/− (n = 48), Ldlr−/− (n = 24), DR4tg (n = 24), and C57Bl/6 (B6) background (n = 24) mice were fed HFHC or regular diet (RD) for 12 weeks. Blood samples were analyzed for serum lipoproteins using a colorimetric assay. C-reactive protein (CRP) and oxidized LDL (OxLDL) were measured using ELISA. Atherosclerosis in the aortas was assessed using the lipid stain, Sudan IV. The presence of citrulline in atherosclerotic plaque was determined by immunohistochemistry. ResultsSera low-density lipoprotein cholesterol (LDL-C) levels were higher in HFHC-fed Ldlr−/− versus DR4tgLdlr−/−-; p = 0.0056, but the aortic plaque burden and degree of citrullination in the plaque were similar for these two strains. The ratio of pro-atherogenic OxLDL to LDL levels was higher in DR4tgLdlr−/− than Ldlr−/−mice; p = 0.0017. All mice had an increase in CRP when fed a HFHC diet, most pronounced for DR4tgLdlr−/−; p = 0.0009. There were no significant sex differences for DR4tgLdlr−/− mice; however, male Ldlr−/− mice had worse atherosclerosis. B6 and DR4tg mice did not have significant elevations in serum cholesterol levels and did not develop atherosclerosis. ConclusionsExpression of HLA-DRB1 resulted in an elevation of OxLDL and a reduction in the male bias for atherosclerosis, mimicking what is observed in RA.

619-P: An Isocaloric High Saturated Fat Diet Increases Endogenous Cholesterol Production Which Is Reversed by a Protein-Enriched Diet in Normal-Weight Humans

Lathosterol is a marker of endogenous cholesterol synthesis whereas plant sterols (e. g. campesterol) reflect cholesterol absorption. Obesity and type 2 diabetes mellitus are associated with increased endogenous cholesterol production and decreased cholesterol absorption. Only few studies evaluated cholesterol homeostasis under isocaloric nutritional conditions. This study investigated endogenous cholesterol production in healthy humans after consumption of isocaloric diets enriched with carbohydrates (KH) or saturated fat (HF) or protein (HP). 24 normal weight participants (women and men, age 18 - 70) were investigated for 18 weeks. An isocaloric diet rich in carbohydrates (55% carbohydrates, 30% fat, 15% protein, KH) was applied followed by an isocaloric diet rich in saturated fat (40% carbohydrates, 45% fat, 15% protein, HF) and finally followed by an isocaloric diet enriched with proteins (45% carbohydrates, 30% fat, 25% protein, HP); each for 6 weeks. Body weight (BW), serum total and LDL cholesterol and serum lathosterol and campesterol levels were analyzed after the KH period, after one week (HF1) and 6 weeks (HF6) of the HF and after the HP period. BW did not change during the study. Serum total and LDL cholesterol increased from 4.38±0.2 and 2.74±0.2 mmol/L, respectively at KH to 4.82±0.2 and 2.97±0.2 mmol/L, respectively at HF6 (both P&amp;lt;0.01) and were decreased back to KH levels at HP. Serum lathosterol levels increased 1.26-fold and 1.16-fold, respectively at HF1 and HF6 (P&amp;lt;0.05 compared to LF), however decreased by 10.1% at HP (compared to KH levels, P&amp;lt;0.05). Serum campesterol levels moderately decreased at HF1 and HF6 and were restored to KH levels at HP (P&amp;lt;0.01 compared to HF6). These data show that composition of macronutrients are responsible for diet induced elevation of serum cholesterol levels due to an increased endogenous cholesterol production in normal weight humans regardless of the energy content of the diet. Disclosure M.Kruse: None. S.Matysik: None. D.Hoffmann: None. T.Frahnow: None. A.F.Pfeiffer: Advisory Panel; Abbott Diabetes, Speaker's Bureau; Novo Nordisk, Sanofi-Aventis Deutschland GmbH. Funding German Federal Ministry of Education and Research (0315424)

Probiotics supplementation attenuates high cholesterol diet-induced hypercholesterolemia in rat model

Hypercholesterolemia is characterized by elevated total serum cholesterol levels, reflecting a high LDL (low-density lipoprotein cholesterol) level, a high TG (triglyceride) level and a low HDL (high-density lipoprotein cholesterol) level. Hypercholesterolemia may cause cardiovascular diseases such as heart attack, stroke and coronary artery diseases. Nowadays, several drugs like statins that lower serum cholesterol are used to treat hypercholesterolemia. However, the cholesterol-lowering drugs have side effects including liver damage and kidney failure. For these reasons, alternatives like probiotics are expected to attenuate hypercholesterolemia instead. Recent studies have shown that probiotics protect against hypercholesterolemia and liver dysfunction via gut-liver axis. Probiotics such as lactic acid bacteria (LAB) may modulate gut microbiota, regulate lipid metabolism and lead to alleviate liver disease. This study aims to determine whether LABs have a protective effect on hypercholesterolemia. LAB strains were selected by acid tolerance, bile tolerance, and antibiotic activity through in vitro screening. 6-week SD rats were fed normal diet or high cholesterol diet (HCD) for 7 weeks. Treatment groups were fed HCD with statin and LABs respectively. LAB supplements effectively improved serum lipid profiles. LABs prevented HCD-induced intestinal and liver damage by enhancing tight junction, reducing inflammation. LABs suppressed lipid accumulation in the liver and enhanced the inhibition of the liver toxicity. Also, LAB supplements changed HCD-induced gut microbiota composition and influenced diversity of gut microbiome. The concentration of bile acid and short chain fatty acids in feces were increased by LAB supplements. Thus, results suggest that LABs are potential therapeutic agents for HCD-induced intestine and liver dysfunction. This work is supported by Cellbiotech Co., Ltd. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Abstract 1741: Inhibition of pcsk9 impairs the development of vessel co-option and potentiates anti-angiogenic therapy in colorectal cancer liver metastases

Abstract Colorectal cancer liver metastatic (CRCLM) tumours present as two main histopathological growth patterns (HGPs) including desmoplastic HGP (DHGP) and replacement HGP (RHGP). The DHGP tumours obtain their blood supply by sprouting angiogenesis, whereas the RHGP tumours utilize an alternative vascularisation known as vessel co-option. In vessel co-option, the cancer cells hijack the mature sinusoidal vessels to obtain blood supply. Vessel co-option has been reported as an acquired mechanism of resistance to anti-angiogenic treatment in CRCLM. Herein, we show the connection between serum cholesterol concentration and vessel co-option development in CRCLM. Our clinical data suggested that the elevation of serum cholesterol levels correlates with the risk of developing vessel co-opting tumours. Moreover, inhibition of PCSK9, the key modulator of cholesterol metabolism, significantly attenuated the development of vessel co-opting CRCLM tumours and sensitized the tumours to anti-angiogenic therapy in vivo. Altogether, these data suggest the importance of cholesterol in the development of vessel co-option tumours and propose that inhibiting PCSK9 is a promising strategy to overcome resistance to anti-angiogenic therapy in CRCLM. Citation Format: Miran Rada, Lucyna Krzywon, Audrey Kapelanski-Lamoureux, Stephanie Petrillo, Andrew Reynolds, Anthoula Lazaris, Nabil Seidah, Peter Metrakos. Inhibition of pcsk9 impairs the development of vessel co-option and potentiates anti-angiogenic therapy in colorectal cancer liver metastases [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1741.

Dyslipidemia And Nephropathy In Diabetes Mellitus: A Review

The prolonged increase of blood glucose give rise to complications of diabetes- premature atherosclerosis (including cardiovascular diseases and stroke), retinopathy, nephropathy and neuropathy. The lipid abnormality (dyslipidemia) associated with type 2 diabetes predominantly consists of elevated triglycerides and decreased HDL cholesterol levels. The incident of dyslipidemia in male is higher in comparison to female type 2 diabetic patients. It was also observed that type 2 diabetic patients with higher BMI has higher chance of developing dyslipidemia Diabetic nephropathy is one of the main microvascular complication of diabetes. In diabetic subjects, a major cause of morbidity and mortality is diabetic nephropathy (DN). Diabetic patients are in risk for the development of dyslipidemia and Diabetic nephropathy. Hyperglycemia causes lipid derangement and nephropathy. Elevated levels of serum cholesterol, triglycerides and lipoproteins are the main lipid derangements in diabetes which are common risk factor for coronary artery disease. It is found that elevated blood glucose levels and duration of diabetes are responsible for nephropathy and microalbuminuria. However Apo B and Lp(a) increases in the microalbuminuria and macroalbuminuria respectively.

The Interaction Between Age and Risk Factors for Diabetes and Prediabetes: A Community-Based Cross-Sectional Study.

This study aimed to investigate the interaction between age groups and risk factors for diabetes and prediabetes in Shanghai communities and to identify the effect of age on other risk factors for diabetes and prediabetes. This study recruited 3540 participants with undiagnosed diabetes or prediabetes in 14 communities in Shanghai from February to August 2019. All participants underwent a comprehensive examination, including filling out a detailed questionnaire, physical examination, 75 g oral glucose tolerance test, and blood sample collection. In addition, logistic regression was used to analyze the interaction between age and risk factors for prediabetes and diabetes. The statistical analysis included 2776 people. In this study, the prevalence of diabetes and prediabetes were 15.1% and 52.3%, respectively. The prevalence of diabetes and prediabetes is higher in the elderly than in the middle-aged group. Among the risk factors for diabetes, overweight was associated with higher age (P-interaction 0.028). In addition, among the risk factors for prediabetes, a high level of education was associated with higher age (P-interaction 0.039) and elevated serum cholesterol level was associated with lower age (P-interaction 0.019). This study confirmed an interaction between age and other influencing factors, which may be important in explaining differences in risk factors for diabetes and prediabetes in the middle-aged and elderly populations. Community health facilities can provide health guidance to people of different age groups to prevent and control prediabetes and diabetes.

Burden and correlates of significant liver fibrosis among HIV-infected and uninfected adults in urban Uganda.

Following chronic inflammation and other disease specific factors, the risk of liver disease is believed to be higher among HIV-infected patients than in the general population despite shared risk factors. Understanding this differentiated burden and its drivers will inform policy and priority populations for intervention. This was a cross sectional study among 516 adults attending care clinics in Kampala Uganda. Significant liver fibrosis (SLF) was defined as liver stiffness measurement ≥7.2 KPa identified by Fibroscan®. Data analyses were stratified by HIV status and we performed logistic regression performed to identify correlates. The prevalence of SLF was higher among HIV un-infected patients ((24% Vs 14%; p0.004). Overall HIV-uninfected patients were more likely to be overweight and or obese, with elevated serum cholesterol levels. Elevated measurement of fatty change in the liver (CAP scores >248 dB/m) was associated with SLF among HIV un-infected patients (OR 2.3 CI (1.0-5.2); p = 0.046). Low nadir CD4 counts (200cell/mm3) was predictive of SLF among HIV-infected patients (OR 3.3 CI (1.0-10.7); p = 0.05). The prevalence of SLF was unexpectedly higher among HIV un-infected than HIV affected patients attending care clinics in urban Uganda. This observed burden is most likely driven by non-alcoholic fatty liver disease (NAFLD) resulting from metabolic syndrome.

Processing Alaska Pollock Protein (Theragra chalcogramma) into Kamaboko Protein Mitigates Elevated Serum Cholesterol and Postprandial Glucose Levels in Obese Zucker fa/fa Rats

Fish paste products such as kamaboko (KB) are traditional Japanese foods prepared from fish meat. The health-promoting properties of fish proteins and their lysates include improving glucose and lipid metabolism. Although the KB manufacturing process and quality have been examined, limited studies have reported the health-promoting function of KB. This study aimed to evaluate the effects of processing Alaska pollock protein (APP) into KB protein (KBP) on serum lipids levels and postprandial glucose tolerance. Obese male Zucker fa/fa rats were fed on different diets for 4 weeks as follows: APP group, fed on a diet in which APP constituted 25% of total protein intake; KBP group, fed on a diet with APP-processed protein as the protein source; control group, fed on a diet with 100% casein as the protein source. Compared with those in the control group, the serum total cholesterol (TC) level was reduced and the elevated postprandial blood glucose level was mitigated during the high-carbohydrate meal tolerance test in the APP and KBP groups. Further, KBP exerted significantly higher effects on serum TC levels and glucose tolerance than APP.

Correlation of Serum Cholesterol and Bone Mineral Density in post Menopausal Women

Background: To find a correlation between serum cholesterol and Bone mineral density in post menopausal women&#x0D; Methods: The experimental group consisted of 100 females at postmenopausal age, in which by the DEXA method was diagnosed osteoporosis while the control group consisted of 100 females in a postmenopausal age but without diagnosed osteoporosis who served as controls.&#x0D; Results: Postmenopausal women in the BMI range 18.5 to 25 (normal)were only included in the study. Others were excluded from the study to avoid confounding factors. The mean BMI in women with osteoporosis was 22.03±1.54 kg/mt2 and in Group-II was 21.09±2.12 kg/mt2. The results were statistically insignificant. Analyzing the average values of serum cholesterol in our study,we found that the mean cholesterol level in group-I was 216.32 ±33.12 mg/dl and 182.32 ±52.10 mg/dl in group-II. The mean cholesterol level was significantly higher in women with osteoporosis.&#x0D; Conclusion: On the decrease in bone mineral density and osteoporosis in postmenopausal women influence many risk factors. Preventive strategies for development of osteoporosis should be initiated in women with elevated serum cholesterol levels.&#x0D; Keywords: Osteoporosis, Menopause, Lipid Profile, BMI.

Dioscin Ameliorates Hyperuricemia-Induced Atherosclerosis by Modulating of Cholesterol Metabolism through FXR-Signaling Pathway

Hyperuricemia is one of the independent risk factors for atherosclerotic cardiovascular disease. Herein, we investigate the association between uric acid and cholesterol metabolism and the effect of dioscin on the prevention of hyperuricemia-induced atherosclerosis. In the potassium oxonate-treated ApoE−/−−/− mice, atherosclerosis was accelerated along with elevated serum cholesterol levels in the hyperuricemic state, which can be ameliorated by dioscin. Together with the in vitro assays, we found that the effect of dioscin was at least partially through the regulation of the farnesoid X receptor (FXR) -small heterodimer partner (SHP) -7α-hydroxylase (CYP7A1) signaling pathway in the liver. Tigogenin (a metabolite of dioscin) suppressed FXR activation and increased CYP7A1, resulting in an increased conversion rate of cholesterols into bile acids. Further clinical study revealed that treatment with a dioscin-enriched preparation decreased serum cholesterol levels in individuals with hyperuricemia. In summary, this study demonstrated a slowdown effect of dioscin on the progression of hyperuricemia-induced atherosclerosis.

Abstract 423: Imatinib Promotes Reverse Cholesterol Transport And Elevates Sr-bi

Dyslipidemia is a cardiovascular risk factor for coronary artery disease and atherosclerosis that is characterized by elevated serum cholesterol and lipid levels. Although high-density lipoprotein-associated cholesterol (HDL-C) is associated with reduced risk of cardiovascular events, targeted therapy to increase HDL-C levels have been unsuccessful in altering outcomes of associated atherosclerotic disease. Single nucleotide polymorphisms in SCARB1 , the gene that encodes HDL receptor Scavenger Receptor B1 (SR-BI), are associated with dyslipidemia and atherosclerotic cardiovascular disease. We were the first to identify inherited mutations in SCARB1 that segregate with disease in a family with severe coronary artery disease and dyslipidemia, including elevated HDL. Our findings suggest that HDL function (vs. HDL-C concentration) may be a promising target for cholesterol-based therapy. Here, we performed an unbiased high throughput drug screen with 788 FDA-approved compounds, using HepG2 cells to measure endogenous HDL binding. We identified five compounds that significantly increased endogenous HDL binding: imatinib, trimethoprim, eszopiclone, clemastine, and mepenzolate, of which, imatinib was the only compound to increase SR-BI expression. Imatinib is a tyrosine kinase inhibitor that is a chemotherapeutic agent designed to treat individuals with chronic myeloid leukemia. Limited clinical evidence suggests a reduction in total cholesterol with 400mg/day imatinib. Additionally, imatinib treatment (150mg/kg) in mouse models of atherosclerosis reduces total cholesterol. Yet, no data is available on the effects of imatinib on HDL and reverse cholesterol transport. We have found that imatinib promotes HDL binding and SR-BI expression in vitro . Furthermore, in wildtype C57Bl/6 mice on a high fat, high cholesterol diet, imatinib treatment (50mg/kg) was sufficient to decrease plasma total cholesterol, HDL-C and triglyceride levels and elevate hepatic SR-BI expression. In summary, our data supports the exploration of imatinib-mediated SR-BI regulation, HDL metabolism, and RCT pathway to identify new therapeutic targets for dyslipidemia.

The Role of High-Density Lipoprotein in Lowering Risk of Dementia in the Elderly: A Review.

Dementia is one of the major causes of disability and hospitalization in the elderly. As far as non-invasive markers of dementia are concerned, we only have age and Apolipoprotein-E (Apo-E) gene, which can be considered as clinically relevant. Modifiable risk factors have been found to be the cause in one-third of the patients who develop dementia. The compatible data supporting the same, in particular for dyslipidemia, is limited, which in turn makes it difficult to devise prevention and interventional methods for both dementia and mild cognitive impairment. Hence, the objective of the review is to summarize the findings on the relation established between the high-density lipoprotein type C( HDL-C) levels and lower the chance of dementia in the elderly, and the possible role of HDL-C as a potential predictive biomarker for cases of dementia in elderly people.Dyslipidemia, a known risk factor for the occurrence of cardiovascular diseases, seems to be linked to Alzheimer’s disease. Elevated levels of serum cholesterol in mid-adult life increases the risk of dementia in older age. But elevated high-density lipoprotein (HDL) level and its principal apolipoprotein A-I (ApoA-I ) equates with a low risk of dementia in the elderly populationHDL cholesterol has been found to promote endothelial nitric oxide synthase activity which in turn reduces the neural and vascular inflammation and suppresses vascular adhesion thereby exhibiting its vasoprotective function. It has been believed that all these factors have a role to play in the pathogenesis of dementia.The relation between the higher levels of HDL cholesterol or its key protein component ApoA-I and the lower dementia prevalence in the elderly had been documented in numerous observational studies. Some studies have reported conflicting results. Yet, observational studies measuring the baseline HDL level in middle age found a significant association between HDL level and dementia risk in the elderly, whereas those studies measuring HDL cholesterol level only in old age found no association. Likewise, a significant association between HDL cholesterol and dementia risk has been reported with studies that carry through to 10 years or longer. However, the studies with follow-up of fewer than 10 years had failed to document any such association between HDL cholesterol and dementia. HDL assays may also be used as a predictive biomarker for dementia patients to target the interventions. Although statins do not target HDL directly but can be an area of interest for dementia.

Effect of activation of liver X receptor alpha on cardiac & hepatic ABCC10 and SLC17A5 drug transporters in hypercholesterolemic rat model

BackgroundLiver x receptor α (LXRα) is a ligand-activated transcription factor belonging to the nuclear receptor superfamily. Oxysterols (endogenous oxidized cholesterol derivatives) are the most potent endogenous LXRα-agonist. LXRα has a direct impact on several members of drug transporter superfamilies; ATP-binding cassette (ABC) and solute linked carrier (SLC). ObjectiveThe current study aimed to investigate the effect of LXRα-activation by either endogenous oxysterols or a synthetic LXRα-agonist (LXRa) such as TO901317 on hepatic and cardiac gene expression of ABCC10 and SLC17A5 drug transporters in an experimentally hypercholesterolemic rat model. Methods48 male rats were divided randomly into four groups (n = 12); control group rats received vehicle; hypercholesterolemic group (HCH group) rats received diet contain 2.5% cholesterol &deoxycholic acid for 8 weeks; (LXRa group) rats were fed standard pellet chow for 8 weeks, then a single dose of LXRa was administered (IP) at a dose of 10 mg/kg; (HCH + LXRa group) rats received diet contain 2.5% cholesterol &deoxycholic acid for 8 weeks, then a single dose of LXRa was administered (IP) at a dose of 10 mg/kg. ResultsOur findings revealed that hypercholesterolemia and LXRa significantly activated LXRα to varying degrees in both hepatic and cardiac tissues with subsequent alteration of LXRα and ABCC10 gene expression. Whereas, SLC17A5 gene expression was primarily affected by elevated serum cholesterol level and unmediated via LXRα-activation. ConclusionsAccordingly, it was concluded that ABCC10 is a specific LXRα-target gene and that LXRα autoregulates its own expression in rats.

Prevalence and Risk Factors of Prediabetes in Madurai City

Type 2 Diabetes is common today among people irrespective of age and as a known fact India has high prevalence of it. Preventing this growing rate of Type 2 Diabetes can be done by making prediabetes screening a mandatory measure as it poses a high risk factor. Hence, this study focuses on the prevalence and risk factors of prediabetes in Madurai City. A cross-sectional survey among people aged above 18 years was conducted and sixteen prediabetes screening centers were set up in different places in Madurai after ethical clearance. 1050 individuals volunteered with prior consent. Their demographics, anthropometric measurements, diets, physical activity, and medical history including blood pressure and venous fasting plasma glucose were collected. It was classified as prediabetes if the fasting plasma glucose was &gt;100 mg/dl and &lt;126 mg/dl and were not previously diagnosed with diabetes. Statistical significance for pair wise comparisons was assessed by one-way ANOVA test. Fasting blood sugar was computed with age, weight, body mass index (BMI), family history, physical activity, polycystic ovarian disease, and gestational diabetes mellitus. Chi square test was used to compare the categorical outcomes between the study groups. P value &lt;0.05 was considered statistically significant. 15% were prediabetes and other contributing factors found were family history, elevated serum cholesterol levels and blood pressure, BMI, and lifestyle changes. Therefore, the study suggests that lifestyle modifications among prediabetes like strict calorie restriction, low fat and high fiber rich food with regular exercise will help prevent diabetes.

Comparative Effect of Bergamot Polyphenolic Fraction and Red Yeast Rice Extract in Rats Fed a Hyperlipidemic Diet: Role of Antioxidant Properties and PCSK9 Expression.

Elevated serum cholesterol levels, either associated or not with increased triglycerides, represent a risk of developing vascular injury, mostly leading to atherothrombosis-related diseases including myocardial infarction and stroke. Natural products have been investigated in the last few decades as they are seen to offer an alternative solution to counteract cardiometabolic risk, due to the occurrence of side effects with the use of statins, the leading drugs for treating hyperlipidemias. Red yeast rice (RYR), a monacolin K-rich natural extract, has been found to be effective in counteracting high cholesterol, being its use accompanied by consistent warnings by regulatory authorities based on the potential detrimental responses accompanying its statin-like chemical charcateristics. Here we compared the effects of RYR with those produced by bergamot polyphenolic fraction (BPF), a well-known natural extract proven to be effective in lowering both serum cholesterol and triglycerides in animals fed a hyperlipidemic diet. In particular, BPF at doses of 10 mg/Kg given orally for 30 consecutive days, counteracted the elevation of both serum LDL cholesterol (LDL-C) and triglycerides induced by the hyperlipidemic diet, an effect which was accompanied by significant reductions of malondialdehyde (MDA) and glutathione peroxidase serum levels, two biomarkers of oxidative stress. Furthermore, the activity of BPF was associated to increased HDL cholesterol (HDL-C) levels and to strong reduction of Proprotein convertase subtilisin/kexin type 9 (PCSK9) levels which were found increased in hyperlipidemic rats. In contrast, RYR at doses of 1 and 3 mg/Kg, produced only significant reduction of LDL-C with very poor effects on triglycerides, HDL-C, glutathione peroxidase, MDA and PCSK9 expression. This indicates that while BPF and RYR both produce serum cholesterol-lowering benefits, BPF produces additional effects on triglycerides and HDL cholesterol compared to RYR at the doses used throughout the study. These additional effects of BPF appear to be related to the reduction of PCSK9 expression and to the antioxidant properties of this extract compared to RYR, thereby suggesting a more complete protection from cardiometabolic risk.