Hypercholesterolemic Group Research Articles

Effect of Olive Pomace Oil on Cardiovascular Health and Associated Pathologies.

Background: olive pomace oil (OPO) is a nutritionally relevant fat due to its high oleic acid content (C18:1) and the presence of a wide range of minor bioactive components. Although numerous in vitro and preclinical studies have been developed to study some of its characteristic components, the health effect of prolonged OPO consumption is unknown. Methods: a randomised, blinded, cross-over, controlled clinical trial was carried out in 31 normocholesterolemic and 37 hypercholesterolemic subjects. Participants consumed 45 g/day of OPO or sunflower oil (SO) for 4 weeks, each preceded by a 3-week run-in/wash-out phase with corn oil (CO). Results: regular consumption of OPO and SO had no statistically significant effect on any of the markers related to lipid profile, blood pressure, and endothelial function in both groups, except for eNOS levels, which were close to statistical significance due to the effect of oil (OPO and SO) (p = 0.083). A decrease in visceral fat (p = 0.028) in both groups was observed after OPO intake, accompanied by an increment of leptin (p = 0.017) in the hypercholesterolemic group. Conclusion: reducing visceral fat after prolonged OPO intake might contribute to improve cardiometabolic status, with a potentially positive effect on the vascular tone. Further clinical trials are needed to confirm the present results.

α-Subunit Tyrosine Phosphorylation Is Required for Activation of the Large Conductance Ca2+-Activated Potassium Channel in the Rabbit Sphincter of Oddi

Large conductance Ca2+-activated potassium (BKCa) channels are regulated by intracellular free Ca2+ concentrations ([Ca2+]i) and channel protein phosphorylation. In hypercholesterolemia (HC), motility impairment of the sphincter of Oddi (SO) is associated with abnormal [Ca2+]i accumulation in smooth muscle cells of the rabbit SO (RSOSMCs), which is closely related to BKCa channel activity. However, the underlying mechanisms regulating channel activity remain unclear. In this study, an HC rabbit model was generated and used to investigate BKCa channel activity of RSOSMCs via SO muscle tone measurement invitro and manometry invivo, electrophysiological recording, intracellular calcium measurement, and Western blot analyses. BKCa channel activity was decreased, which correlated with [Ca2+]i overload and reduced tyrosine phosphorylation of the BKCa α-subunit in the HC group. The abnormal [Ca2+]i accumulation and decreased BKCa channel activity were partially restored by Na3VO4 pretreatment but worsened by genistein in RSOSMCs in the HC group. This study suggests that α-subunit tyrosine phosphorylation is required for [Ca2+]i to activate BKCa channels, and there is a negative feedback between the BKCa channel and the L-type voltage-dependent Ca2+ channel that regulates [Ca2+]i. This study provides direct evidence that tyrosine phosphorylation of BKCa α-subunits is required for [Ca2+]i to activate BKCa channels in RSOSMCs, which may be the underlying physiological and pathologic mechanism regulating the activity of BKCa channels in SO cells.

Achilles Tendon Softness and Thickness in Patients With Hypercholesterolemia.

BackgroundHypercholesterolemia is a condition where blood levels of cholesterol are high. It is of two types: The first type is familial hypercholesterolemia, which is hereditary, and the second one is due to diseases like diabetes, thyroid, etc. Achilles tendon xanthomas are noted in both types of hypercholesterolemia, which can be used as an indicator that predicts early cardiovascular disease. The aim of the study is to estimate the Achilles tendon thickness (ATT) and softness among hypercholesterolemia patients and to find the correlation between ATT and total cholesterol.MethodologyA hospital-based cross-sectional, analytical study was done in a tertiary care hospital, Salem, for eight months. Patients of age over 18 years of both sexes who came for screening of total cholesterol in the outpatient department were included in the study. Those patients with a history of previous leg injury involving the Achilles tendon were excluded from the study. A pre-structured questionnaire was used to collect the data, and analysis was done using Statistical Package for the Social Sciences (SPSS) v20 (IBM Corp., Armonk, NY). The analysts performed the Pearson correlation test to determine the correlation between two continuous variables. A p-value of less than 0.05 was used to indicate statistical significance.ResultsIn this study, there are 40 participants in the normal group and about 60 participants in the secondary hypercholesterolemia group. The mean ATT value among males and females was 9.3 and 6.1 mm, respectively. A positive correlation was noted between the ATT and total cholesterol value (p-value = 0.0001).ConclusionThe thickness and softness of the Achilles tendon are positively correlated with the serum total cholesterol level. Males are the group where this correlation is most significant. As a result, men have a higher risk of developing Achilles tendon thickening than women. The thickness of the Achilles tendon can therefore be one of the early signs of high cholesterol levels. The clinician can utilize this indicator to evaluate early abnormal cardiac illness.

Increased interleukin-6 and TP53 levels in rotator cuff tendon repair patients with hypercholesterolemia.

A previous study reported that hyperlipidemia increases the incidence of tears in the rotator cuff tendon and affects healing after repair. The aim of our study was to compare the gene and protein expression of torn rotator cuff tendons in patients both with and without hypercholesterolemia. Thirty patients who provided rotator cuff tendon samples were classified into either a non-hypercholesterolemia group (n=19, serum total cholesterol [TC] <200 mg/dL) and hypercholesterolemia group (n=11, serum TC ≥240 mg/dL) based on their concentrations of serum TC. The expression of various genes of interest, including COL1A1, IGF1, IL-6, MMP2, MMP3, MMP9, MMP13, TNMD, and TP53, was analyzed by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). In addition, Western blot analysis was performed on the proteins encoded by interleukin (IL)-6 and TP53 that showed significantly different expression levels in real-time qRT-PCR. Except for IGF1, the gene expression levels of IL-6, MMP2, MMP9, and TP53 were significantly higher in the hypercholesterolemic group than in the non-hypercholesterolemia group. Western blot analysis confirmed significantly higher protein levels of IL-6 and TP53 in the hypercholesterolemic group (p<0.05). We observed an increase in inflammatory cytokine and matrix metalloproteinase (MMP) levels in hypercholesterolemic patients with rotator cuff tears. Increased levels of IL-6 and TP53 were observed at both the mRNA and protein levels. We suggest that the overexpression of IL-6 and TP53 may be a specific feature in rotator cuff disease patients with hypercholesterolemia.

Metabolic Disorders and Risk of Portal Vein Thrombosis in Liver Cirrhosis: A Systematic Review and Meta-Analysis.

Portal vein thrombosis is considered to be an indicator of worse outcomes in patients with hepatic cirrhosis. More and more evidence shows that metabolic disorders are noticeable pro-thrombotic factors. However, whether or not metabolic disorders increase the risk of cirrhotic portal vein thrombosis is controversial. We aim to quantify the magnitude of the association between metabolic disorders and the risk of cirrhotic portal vein thrombosis. Databases were searched for papers to identify studies in which metabolic disorders were compared in liver cirrhosis with or without portal vein thrombosis. Based on data from the eligible studies, metabolic disorders related to portal vein thrombosis included diabetes mellitus, nonalcoholic fatty liver disease, hypercholesterolemia, and body mass index. Pooled adjusted odds ratios with 95% CIs were calculated. Data for 22 studies with a total of 57 371 portal vein thrombosis cases and 3 979 015 participants were included. Statistically significant pooled odds ratios for portal vein thrombosis were obtained for diabetes mel- litus (odds ratio 1.80, 95% CI 1.42-2.28), nonalcoholic fatty liver disease (odds ratio 1.61, 95% CI 1.34-1.95), and hypercholesterolemia (odds ratio 3.59, 95% CI 1.83-7.03). Body mass index was likely irrelevant with cirrhotic portal vein thrombosis (odds ratio 1.01, 95% CI 0.87-1.17), both in overall and subgroup meta-analyses. Significant heterogeneities among studies were observed, except for the hypercholesterolemia group. Metabolic disorders, such as diabetes mellitus, nonalcoholic fatty liver disease, and hypercholesterolemia, increased the risk of portal vein thrombosis in cirrhotic patients by 1.80-fold, 1.61-fold, and 3.59-fold, respectively. Body mass index did not appear to be a risk predictor of cirrhotic portal vein thrombosis. Further, well-designed clinical and mechanistic studies are required to strengthen the arguments, especially in obese patients.

Endothelial Microparticles as Potential Biomarkers in the Assessment of Endothelial Dysfunction in Hypercholesterolemia.

Background and Objectives: Endothelial microparticles (EMP) particularly CD31+/42−/AV+, CD144+/AV+ and CD62e+/AV+ have been reported as having increased in cardiovascular-related diseases, making them potential biomarkers for endothelial dysfunction. This study aimed to compare these EMPs in patients with hypercholesterolemia and healthy controls and to correlate their levels with endothelium-dependent vasodilation (EDV) assessed via pulse wave analysis (PWA); an established method of assessing endothelial function. Materials and Methods: EMPs from 88 subjects (44 hypercholesterolemia patients and 44 controls) were quantified from whole blood using flow cytometry analysis. Endothelial function was determined using PWA combined with pharmacological challenge. Results: CD31+/42−/AV+ (3.45 ± 4.74 count/µL vs. 1.33 ± 4.40 count/µL; p = 0.03), CD144+/AV+ (7.37 ± 12.66 count/µL vs. 1.42 ± 1.71 count/µL; p = 0.003) and CD62e+/AV+ (57.16 ± 56.22 count/µL vs. 20.78 ± 11.04 count/µL; p < 0.001) were significantly elevated in the hypercholesterolemic group compared with the controls, respectively. There was a significant inverse moderate correlation between all circulating EMPs and EDV: CD31+/42−/AV+ (r = −0.36, p = 0.001), CD144+/AV+ (r = −0.37, p = 0.001) and CD62e+/AV+ (r = −0.35, p = 0.002). Conclusions: All EMPs were raised in the patients with hypercholesterolemia, and these values correlated with the established method of assessing endothelial function.

Maternal High-Fat Diet Aggravates Allergic Asthma in Offspring via Modulating CD4+ T-Cell Differentiation.

Maternal improper nutrition has been reported to trigger respiratory disorders in offspring. Here, we characterized the effects of high-fat environment in the fetal period on mice and human cord blood CD4+ T-lymphocytes, and investigated their roles in susceptibility to asthma. Mice born to mothers that consumed a high-fat diet (HFD) throughout the gestation period were sensitized by ovalbumin to establish an experimental asthma model. To further extrapolate to humans, we collected cord blood from neonates of hypercholesterolemic (HC) mothers (n = 18) and control mothers (n = 20). In mice, aggravated airway hyperresponsiveness and inflammation revealed that maternal high-fat diet could lead to exacerbated allergic asthma in adult offspring. It was partially due to augmented activation and proliferation of CD4+ T-cells, where upregulated klf2 mRNA levels may be potentially involved. Notably, naïve HFD CD4+ T-cells had enhanced TH2-based immune response both in vivo and in vitro, resulting from DNA hypomethylation of the Il-4 promoter region. Moreover, in human, TH2 cytokines transcripts were enhanced in CD4+ T-cells of the HC group, which was associated with an increased risk of developing allergic diseases at 3 years old. Together, our study indicated that early life improper nutrition-triggered epigenetic changes in T-cells may contribute to long-lasting alterations in allergic diseases.

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.

Cilostazol attenuates cardiac oxidative stress and inflammation in hypercholesterolemic rats.

Atherosclerosis is a multifactorial chronic disease associated with pro-inflammatory and pro-oxidative cardiovascular states. Cilostazol, a selective phosphodiesterase 3 inhibitor (PDE3), is clinically used in the treatment of intermittent claudication and secondary prevention of cerebral infarction. The aim of this study was to evaluate the cardioprotective effects of cilostazol and the molecular mechanisms involved in hypercholesterolemic rats. Male Wistar rats were divided into four groups: control group (C) and control + cilostazol group (C+CILO), that were fed a standard chow diet, and hypercholesterolemic diet group (HCD) and HCD + cilostazol (HCD+CILO) that were fed a hypercholesterolemic diet. Cilostazol treatment started after 30 days for C+CILO and HCD+CILO groups. Animals were administered cilostazol once a day for 15 days. Subsequently, serum and left ventricles were extracted for evaluation of lipid profile, inflammatory, and oxidative biomarkers. The HCD group displayed increased serum lipid levels, inflammatory cytokines production, and cardiac NF-kB protein expression and decreased cardiac Nrf2-mediated antioxidant activity. Conversely, the cilostazol treatment improved all these cardiac deleterious effects, inhibiting NF-kB activation and subsequently decreasing inflammatory mediators, reestablishing the antioxidant properties through Nrf2-mediated pathway, including increased SOD, GPx, and catalase expression. Taken together, our results indicated that cilostazol protects hypercholesterolemia-induced cardiac damage by molecular mechanisms targeting the crosstalk between Nrf2 induction and NF-kB inhibition in the heart.

Protective Effect of Tiger Nut (Cyperus esculentus L.) on Hypercholesterolemia Rats

The aim of the present work was to investigate the effect of tiger nut on rats suffering from hypercholesterolemia. Forty-eight male albino rats weighing 160 ± 5 g were used in this study. The rats divided into two main groups, the 1st main group (n=6) was fed on the basal diet (-ve control).The 2nd group (n = 6) was fed on hypercholesterolemic diet with addition of 1% cholesterol +0.5% colic acid+10% corn oil to induce hypercholesterolemia. Groups (3-5) were fed on basal diet supplemented with (10, 15, 25%) tiger nut, respectively. Groups (6-8) were fed on hypercholesterolemic diet supplemented with (10, 15, 25%) from tiger nut. The results revealed that all hypercholesterolemic groups which treated with 10%, 15%, and 25% of tiger nut resulted a varied increase in body weight gain, feed intake and feed efficiency ratio. Results declared that there was a significant difference (P≤0.05) among the positive control group and cholesterol groups treated with the different levels of tiger nut in internal organ weights. On the other hand, data showed that there was no significant difference (P≥0.05) in organs weight between the negative control group, and the group which treated with 25% tiger nut rats group. The results showed a significant decrease in AST, ALT, ALP enzymes activity, creatinine, blood urea and uric acid for treated groups as compared with positive control group. Results indicated that hypercholesterolemic rat groups, which treated with 10,15 or 25% tiger nut resulted in significant decreases (P≤0.05) in the values of serum total cholesterol, T.G, LDL-cholesterol, VLDL and LDL-cholesterol but showed mostly significant increase (P≤0.05) in the values of serum HDL-cholesterol compared to control (+ve) group. Tiger nut also, lowered malondialdehyde, while raised glutathione in serum. So, the study recommended using tiger nut in diets to overcome the problems of hypercholesterolemia and also improving the liver and kidney functions. ملخص البحث التأثير الوقائى لحب العزيز على الفئران المصابه بارتفاع مستوى الکولسترول أجريت هذه الدراسة لمعرفة التاثير الوقائى لحب العزيز على الفئران التى تعانى من ارتفاع مستوى الکوليسترول. تم استخدام 48 من ذکور الفئران من سلالة الالبينو يتراوح وزنهم (160±5 جرام).تم تقسيم الفئران الى مجموعتين اساسيتين . المجموعة الاولي وهي المجموعة الضابطة السالبة وتتغذي علي الغذاء الاساسي فقط . المجموعة الثانية تغذت على الغذاء الاساسى بالاضافه الى 1%کوليسترول+05 حمض الکوليک لاحداث ارتفاع فى مستوى الکوليسترول للفئران. المجاميع من (3-5) تغذت علي الغذاء الاساسي فقط بالاضافه الى (25,15,10%) من حب العزيز على التوالى. المجاميع من(6-8) تم تغذيتهم على الغذاء العالى فى مستوى الکوليسترول مع اضافة (25,15,10%) من حب العزيز على التوالى لمدة 12 اسبوع. تشير نتائج تحليل الدم الى ارتفاع کلا من معدل الزيادة فى الوزن ,معدل تناول الطعام ومعدل کفاءة الطعام فى کل المجاميع التى تغذت على الغذاء العالى فى مستوى الکوليسترول عن المجموعه الضابطه السالبه. اوضحت النتائج ان هناک اختلاف فى الوزن الداخلى للاعضاء فى المجموعه الضابطه الموجبه والمجاميع التى تغذت على الکوليسترول و(10,15,25% ) من حب العزيز.بينما لم يکن هناک اختلاف معنوى بين المجموعه الضابطه السالبه والمجاميع الصحيه.اظهرت النتائج انخفاض معنوى فى انزيمات ,AST,ALT اليوريا والکرياتينين وحمض اليورک فى المجاميع التى تمت معالجتها مقارنة بالمجموعة الضابطه الموجبه .اظهرت النتائج انخفاض فى قيم کلا من (الکولسترول الکلى ,الدهون الثلاثيه ,البروتينات ذات الکثافة المنخفضة والبروتينات ذات الکثافة المنخفضة جدا بينما کان هناک غالبا ارتفاع ملحوظ فى قيم البروتينات المرتفعه الکثافة للفئران المصابه بارتفاع مستوى الکولسترول وتغذت على الثلاث مستويات المستخدمه من حب العزيز فى الدراسة . وقد ادت التغذيه على حب العزيز ايضا الى انخفاض مالون داى الدهيد وارتفاع الجلوتاثيون فى السيرم.الترکيب الکيميائى للأحماض الدهنية لحب العزيز مناسب للدفاع والحد من تدهور حاله الدهون .لذلک اوصت الدراسة باهميه استخدام حب العزيز فى الغذاء للتغلب على مشاکل ارتفاع مستوى الکوليسترول وايضا تحسين وظائف الکلى والکبد. الکلمات المفتاحية: الکولسترول – حب العزيز – وظائف الکلى –وظائف الکبد.

Achillea Fragrantissima Ethanolic Extract Exerts Hypocholesterolemia and Hepatic Antioxidant Effects in High Fat-Cholesterol Diet: An Experimental Study

Background: Hypercholesterolemia and oxidative stress consider the main causes for atherosclerotic cardiovascular diseases, that are one of the major non-communicable diseases responsible for more than a third of deaths in Saudi Arabia. Cholesterol-lowering medications as Atorvastatin® (ATOR) are linked to a variety of side effects. Achillea fragarntissima (AF) is a valuable medicinal plant in Saudi Arabia with potent antioxidant activity. Aim: The current study was performed to determine the efficacy of AF in the treatment of hypercholesterolemia through the antioxidant metabolic pathway. Methodology: Dried aerial parts of AF were extracted by ethanol (70%). Induction of hypercholesterolemia in rats was induced through feeding a high fat-cholesterol diet (HFCD) for 8 weeks. Rats were assigned to two main groups; control group (Cont, n=10) rats fed a standard diet, and hypercholesterolemic group (HFCD) (n=40) rats fed HFCD. The HFCD group was further assigned after measured lipid profile to confirm the induction of hypercholesterolemia to HFCD; HFCD+AF (hypercholesterolemic rats treated orally with 500 mg/kg AF); HFCD+ ATOR (hypercholesterolemic rats treated orally with 20 mg/kg ATOR, as a reference drug); and HFCD+AF+ATOR (hypercholesterolemic rats treated orally with AF+ ATOR). Different treatments were ingested to rats for 4 weeks. Results: The results revealed that the HFCD group showed significant hyperlipidemia (elevation of serum TC, TG, LDL-C, and VLDL-C levels concurrent with a reduction in serum HDL-C level); significant disturbance in liver functions (elevation in serum ALT, AST, and ALP enzymes activities); and significant oxidative stress (elevation in hepatic MDA level with a reduction in hepatic SOD activity) compared with the Cont group. Besides, hepatic central vein section showed deposition of large lipid within hepatocytes and abundant focal cell necrosis. Oral treatment with AF, ATOR, and the mixture of the drug and AF produced significant hypocholesterolemia, antioxidant, and improved liver function enzymes, with normalized hepatic central vein tissue compared with the HFCD group. The mixture of AF+ATOR had a superior effect than either treatment alone. Conclusion: In hypercholesterolemic rats, AF may be used to prevent atherosclerosis through improving lipid profile levels, protecting against hepatic oxidative stress, and ameliorating hepatic functions. Thus highlighting its valuable effects in the treatment of atherosclerotic cardiovascular diseases. Keywords: Achillea fragarntissima, lipid profile, hepatic oxidative stress, hepatic function, hypercholesterolemia.

Effect of Hypercholesterolemia on Retina of Adult and Aged Male Albino Rat: A Histological and Immunohistochemical Study

Abstract Introduction Age related degeneration (ARD) is the leading cause of irreversible blindness among old people. Epidemiologic studies have suggested that nutritional parameters such as dietary fat and cholesterol may play a role in the pathogenesis of retinal degeneration. High intake of saturated fat and cholesterol is correlated with a higher risk for early ARD which occurs either directly or through the promotion of vascular pathology. Aim of the work was to evaluate the early histological and immunohistochemical changes of the retina, induced by hypercholesterolemia in adult male albino rat and comparing these changes with similar results in aged male albino rat and to apply a comparative lipid profile biochemical study between the different groups. Materials and methods Forty male albino Sprague Dawley rats were used in the study. They were divided into four groups, ten rats per each; Group I: control adult: aged 3-6 months and group II: control aged: aged 24 months were fed on standard diet, Group III: adult hypercholesterolemic group and group IV: aged hypercholesterolemic group were fed on hypercholesterolemic diet which consisted of the same ingredients of the standard diet except for the cellulose was reduced to (4%) with addition of cholesterol (1%) for duration of 6 weeks. At the end, retinal specimens were collected and processed for light microscopic and immunohistochemical examination. Results The aged rats showed marked disruption of the normal histological architecture of retina and affection of each individual retinal layer. Hypercholesterolemia markedly affected the adult rat retina and aggravated the aged retina. The affected retinae showed marked thinning of the retinal thickness, disorganization of the cell within the neuronal cell layer with decreased number of the cells within ganglion-cell layer. Immunohistochemistry revealed significant increase in retinal reactivity to glial fibrillary acidic protein, vascular endothelial growth factor, caspase 3 and nitric oxide synthase by aging and hyperlipidaemia. Conclusion The present work suggested that hypercholesterolemia is an important risk factor that can accelerates aging of healthy adult retina producing age related retinal degeneration.

The effects of cholesterol accumulation on Achilles tendon biomechanics: A cross-sectional study.

Familial hypercholesterolemia, a common genetic metabolic disorder characterized by high cholesterol levels, is involved in the development of atherosclerosis and other preventable diseases. Familial hypercholesterolemia can also cause tendinous abnormalities, such as thickening and xanthoma (tendon lipid accumulation) in the Achilles, which may impede tendon biomechanics. The objective of this study was to investigate the effect of cholesterol accumulation on the biomechanical performance of Achilles tendons, in vivo. 16 participants (10 men, 6 women; 37±6 years) with familial hypercholesterolemia, diagnosed with tendon xanthoma, and 16 controls (10 men, 6 women; 36±7 years) underwent Achilles biomechanical assessment. Achilles biomechanical data was obtained during preferred pace, shod, walking by analysis of lower limb kinematics and kinetics utilizing 3D motion capture and an instrumented treadmill. Gastrocnemius medialis muscle-tendon junction displacement was imaged using ultrasonography. Achilles stiffness, hysteresis, strain and force were calculated from displacement-force data acquired during loading cycles, and tested for statistical differences using one-way ANOVA. Statistical parametric mapping was used to examine group differences in temporal data. Participants with familial hypercholesterolemia displayed lower Achilles stiffness compared to the control group (familial hypercholesterolemia group: 87±20 N/mm; controls: 111±18 N/mm; p = 0.001), which appeared to be linked to Achilles loading rate rather than an increased strain (FH: 5.27±1.2%; controls: 4.95±0.9%; p = 0.413). We found different Achilles loading patterns in the familial hypercholesterolemia group, which were traced to differences in the centre of pressure progression that affected ankle moment. This finding may indicate that individuals with familial hypercholesterolemia use different Achilles loading strategies. Participants with familial hypercholesterolemia also demonstrated significantly greater Achilles hysteresis than the control group (familial hypercholesterolemia: 57.5±7.3%; controls: 43.8±10%; p<0.001), suggesting that walking may require a greater metabolic cost. Our results indicate that cholesterol accumulation could contribute to reduced Achilles function, while potentially increasing the chance of injury.

Abstract P137: Hypercholesterolemia Aggravates In-stent Restenosis In Rabbits By Escalating Vascular Inflammation

Background: Hypercholesterolemia (HC) has previously been shown to augment restenotic response in several animal models. However, the mechanistic aspects of in-stent restenosis (ISR) on an HC background are not fully understood. Methods: HC was induced in 5 NZW rabbits by hypercholesterolemic diet (HCD) fed for 4 weeks prior to bilateral implantation of stainless steel stents in the iliac location. The diet was continued until sacrifice. In parallel, stents were deployed in the iliac arteries of 5 normocholesterolemic (NC) rabbits. All animals were euthanized 4 weeks after stenting. Harvested arteries were formalin-fixed. The stent struts were dissolved in a mixture of nitric and hydrofluoric acids. The destented arteries were paraffin-embedded, sectioned, stained according to the Verhoeff-vanGieson method, and the lumen area, neointimal thickness, neointimal area, neointima-to-media ratio, and percent of luminal stenosis were determined morphometrically. A semiquantitative scale was used to assess the intensity and spread of TNFa expression by immunohistochemistry (IHC). The prevalence of peri-strut macrophages (MΦ) was determined by IHC as a percentage of a strut circumference infiltrated with MΦ. Results: HC diet drastically increased severity of ISR (Fig). The corresponding values of the lumen area, neointimal thickness, neointimal area, neointima-to-media ratio and percent of luminal stenosis for the groups of NC and HC animals were 1.86±0.44 vs 1.48±0.54 (p&lt;0.05), 0.06±0.02 vs 0.31±0.14 (p&lt;0.0001), 0.66±0.16 vs 2.07±0.56 (p&lt;0.0001), 1.99±0.11 vs 4.57±0.76 (p&lt;0.0001), and 26.35±4.78 vs 57.89±13.71 (p&lt;0.0001). Compared to NC animals, TNFa immunopositivity and MΦ infiltration of peri-strut areas increased in HC group animals 1.81- and 2.58-fold, respectively (p&lt;0.001 for both). Conclusions: The inflammatory response to stent deployment is intensified in HC metabolic conditions, leading to the augmented neointimal expansion and ISR.

Effects of cholesterol and Lactobacillus acidophilus on testicular function.

ObjectiveIn this study, the effects of Lactobacillus acidophilus on testosterone (TES), follicle-stimulating hormone (FSH), luteinizing hormone (LH), androgen-binding protein (ABP), factor-associated apoptosis (FAS), and total cholesterol (TC), as well as histopathological changes, were investigated in male rats fed a high-cholesterol diet. MethodsThe study included three groups. The control (C) group was fed standard-diet for 8 weeks. The hypercholesterolemia (HC) group was fed a 2% cholesterol-diet for 8 weeks. The therapeutic group (HCL) was fed a 2% cholesterol-diet for 8 weeks and administered L. acidophilus for the last 4 weeks. FSH, TES, and FAS levels in testicular tissue were determined using an enzyme-linked immunosorbent assay (ELISA), while another sample was examined histopathologically. LH and ABP levels were determined using ELISA, and serum TC levels were assessed via an autoanalyzer. ResultsIn the HC group, the TC levels were significantly higher and the LH levels were lower (p<0.05) than in the C group. The ABP levels were lower (p>0.05). In the HCL group, the LH and ABP levels were higher (p>0.05) and the TC level significantly lower (p<0.05) than in the HC group. The TES and FSH levels were lower, and the FAS levels were higher, in the HC than in the C group (p<0.05). In the HCL group, levels of all three resembled control levels. Histologically, in the testicular tissue of the HC group, the cells in the tubular wall exhibited atrophy, vacuolization, and reduced wall structure integrity. However, in the HCL group, these deteriorations were largely reversed.Conclusion Supplementary dietary administration of an L. acidophilus to hypercholesterolemic male rats positively impacted testicular tissue and male fertility hormone levels.

Regular transient limb ischemia protects endothelial function against hypercholesterolemic damage in rabbits.

Regular transient limb ischemia (RTLI) can prevent atherosclerosis in hypercholesterolemic rabbits. As endothelial dysfunction is the initial factor leading to atherosclerosis, we investigated the effect of RTLI on endothelial function in hypercholesterolemic rabbits. We randomly allocated 15 New Zealand white rabbits to three groups, five animals per group: the hypercholesterolemic group (Group H), the sham RTLI group (Group S), and the RTLI group (Group L). All rabbits received hypercholesterolemic fodder daily. No intervention was performed on the rabbits in Group H. Rabbits in Group S were kept in hutches, with a deflated cuff applied to their left hind limb for 60 min every day. For rabbits in Group L, RTLI (six cycles of 5-min ischemia and 5-min reperfusion of the left hind limb) was applied once daily for 12 weeks. At the end of week 12, a segment of the abdominal aorta was isolated from each rabbit for in vitro measurement of the endothelium-dependent vasodilation (EDV) response to different concentrations of acetylcholine and the endothelium-independent vasodilation (EIV) response to sodium nitroprusside. The EDV response was significantly higher in Group L than in Groups S and H (p < 0.05), with no significant difference between Groups S and H (p > 0.05). There was no difference in the EIV response among the three groups. RTLI could improve the EDV response, protecting endothelial function against hypercholesterolemic damage.

ANTIHYPERCHOLESTEROLEMIC AND ANTIATHEROGENIC POTENTIAL OF AQUEOUS EXTRACT OF ADANSONIA DIGITATA STEM BARK INDUCED BY HEATED PALM OIL SUPPLEMENTED WITH EGG YOLK IN RAT

Objective: Poor control of hypercholesterolemia which mediated by overproduction of reactive oxygen species and endothelial dysfunction leads to atherosclerosis. The present study aimed to investigate the antihypercholesterolemic and anti-atherogenic effects of Adansonia digitata (AD) in heated palm oil/cholesterol supplemented with egg yolk in rat.&#x0D; Methods: Quantitative phytochemical screening of aqueous extract of A. digitata was carried out to identify the phytoconstituents. In vitro and in vivo antioxidant potential was evaluated. The antihypercholesterolemic and anti-atherosclerosis activity of A. digitata was evaluated by inducing hypercholesterolemia in rats with heated palm oil/cholesterol diet supplemented with egg yolk for 10 w. At the end of the induction period, animals were divided into 5 groups of 8 rats each after 6 w of induction: Group I (normocholesterolemic rat, NCR), Group II (hypercholesterolemia rat, HCR), Group III (Atorvastatin 2 mg/kg), Groups IV (AD. 100 mg/kg) and V (AD. 200 mg/kg). Hemodynamic parameters, lipid profile, atherogenic indices and oxidative stress markers were evaluated.&#x0D; Results: Adansonia digitata significantly reduced the systolic arterial blood pressure (SBP), diastolic arterial blood pressure (DBP), pulsatile pressure (PP) and heart rate compared to the hypercholesterolemic group. Plant extract reveal important flavonoids and phenolic contents and has significant in vivo antioxidant efficacy. The higher dose (200 mg/kg) of the extract significantly reduced in the level of total cholesterol by 27.29 %, triglycerides by 27.60 % and the LDL-c by 36.04 % meanwhile the HDL-c increased by 277.47 % when compared to 5HPOC treated group. Atorvastatin (2 mg/kg) administered in addition to 5HPOC significantly improved in lipid profile as compared to untreated rats. Furthermore, the histopathological examination of aorta of 5HPOC-treated rats indicated that the aqueous extract of A. digitata significantly attenuated atherosclerosis lesions.&#x0D; Conclusion: The aqueous extract of A. digitata possessed antihypercholesterolemic and anti-atherogenic effects via modulation overproduction of reactive oxygen species and endothelial dysfunction.

Health Costs of Older Opioid Users with Pain and Comorbid Hypercholesterolemia or Hypertension in the United States.

This retrospective cross-sectional database study used 2018 Medical Expenditure Panel Survey data to quantify and assess differences in healthcare expenditures between opioid users and non-users among a non-institutionalized sample of older (≥50 years) United States adults with pain in the past four weeks and a diagnosis of comorbid hypercholesterolemia (pain–hypercholesterolemia group) or hypertension (pain–hypertension group). Hierarchical multivariable linear regression models were constructed by using logarithmically transformed positive cost data and adjusting for relevant factors to assess cost differences between groups. Percent difference between opioid users and non-users was calculated by using semi-logarithmic equations. Healthcare costs included inpatient, outpatient, office-based, emergency room, prescription medication, other, and total costs. In adjusted analyses, compared to non-users, opioid users in the pain–hypercholesterolemia and pain–hypertension groups respectively had 66% and 60% greater inpatient expenditure, 46% and 55% greater outpatient expenditure, 67% and 72% greater office-based expenditure, 50% and 60% greater prescription medication expenditure, 24% and 22% greater other healthcare expenditure, and 85% and 93% greater total healthcare expenditure. In conclusion, adjusted total healthcare expenditures were 85–93% greater among opioid users versus non-users in older United States adults with pain and comorbid hypercholesterolemia or hypertension. Future research is needed to identify opioid use predictors among these populations and reduce expenditures.

Progressivity of TNF-α production and miR-29b-3p expression during hypercholesterolemia

Hypercholesterolemia triggers atherosclerosis, characterized by releasing TNF-α and miR-29-3p that may be applicable for biomarker or therapeutic targets. This study was aimed to analyze the correlation between TNF-α production and miR-29b-3p expression during hypercholesterolemia progression. Total 12-male-Sprague Dawley rats weighted of 170-180 gr were randomly divided into normal control group and hypercholesterolemia (HC) group, equally. The Sprague Dawley (SD) rats were given only standard feed for seven weeks, combined with placebo for normal group and 2 ml of cholesterol/200 grBM/day, orally for hypercholesterolemia group. The miR-29b-3p expression analysis was performed by qRT-PCR and TNF-α using ELISA, by followed manufacture procedures. The miR-29b-3, then analyzed using Kruskal-Wallis analysis, whereas TNF-α was analysed using t-test. During, initial week, TNF-α was produced 5.19±0.20 pg/ml in the normal group and significantly different with HC group there was 4.43±0.32 pg/ml, then it significantly increases up to 6.12±0.21 pg/ml in the normal group and 14.10±0.33 in the HC group. Increased of miR-29b-3p expression was occurred in the normal group by from 1.33±0.24-fold change in 1st week to 2.55±0.08 fold change in 8th week, then 1.66x104±1.06x104 to 1.94x104±1.19x104 fold change in HC group.

Baseline Serum Cholesterol Levels Predict the Response of Patients with Advanced Non-Small Cell Lung Cancer to Immune Checkpoint Inhibitor-Based Treatment.

PurposeAlthough predictive markers of immune checkpoint inhibitor (ICI)-based treatments have been extensively studied, with the exception of programmed death ligand 1 (PD-L1), most are not widely used in the clinic due to poor effects or defective practicability. The aim of this study was to identify those patients with high baseline serum cholesterol who benefit from ICI-based treatments.Patients and MethodsPatients with advanced non-small cell lung cancer (NSCLC) treated at Ningbo Medical Center, Li Huili Hospital between August 2017 and December 2019 were enrolled in this retrospective study. The Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) were used to evaluate the efficacy of the ICI-based treatment. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan–Meier survival curves and compared using the log rank test. Univariate and multivariate analyses were conducted using the logistic regression analysis and Cox proportional hazards model. A receiver operating characteristic curve was created, and the area under the curve (AUC) was calculated to compare the predictive value of baseline serum cholesterol with PD-L1 expression for patient response to ICI-based treatment.ResultsIn our cohort of 169 NSCLC patients, the objective response rate (ORR) and disease control rate (DCR) of the treatment were significantly higher in patients with hypercholesterolemia (>5.18 mmol/L) than in those with hypocholesterolemia (ORR: 33.67% vs 14.08%, P=0.004; DCR: 68.37% vs 42.25%, P=0.001). The median PFS was 7.9 months in the hypercholesterolemia group, significantly longer than in the hypocholesterolemia group (4.4 months, 95% CI: 4.620–7.380, P<0.001). The median OS in the two groups were 11 months and 8 months, with 95% CIs of 8.980–10.420 (P<0.001). The AUC for the baseline level of cholesterol was 0.706 (P<0.001), while it was 0.643 (P=0.001) for PD-L1 expression.ConclusionThe baseline serum cholesterol level is predictive of a clinical benefit for advanced NSCLC patients who undergo ICI-based treatment, and hence it is a promising prognostic indicator for ICI-based treatment of NSCLC.