Hypercholesterolemic Group Research Articles

ANTI-HYPERLIPIDEMIA ACTIVITY IN THE VIVO TEST FROM A COMBINATION OF AVOCADO LEAF EXTRACT (Persea americana Mill) AND GINGER RHIZOME (Curcuma xanthorrhiza Roxb) IN MICE WITH HYPERCHOLESTEROLEMIA

Herbal and traditional medicine are two of the main types of treatment in developing countries, including Indonesia. Hyperlipidemia is a condition in which cholesterol levels in the body exceed normal limits, impacting cardiovascular disease. Avocado leaves and temulawak rhizomes have been shown to have antihyperlipidemic effects in animals. This study aimed to determine the anti-hyperlipidemic activity of avocado leaf (Persea americana Mill) and temulawak rhizome (Curcuma xanthorrhiza Roxb) combination extract in cholesterol levels of white male mice Sprague Dawley strain. The subjects of this study consisted of 20 white male mice Sprague Dawley strain (Rattus novergicus) and were divided into five groups: F1 (standard); F2 (hypercholesterolemic group); F3 (1:1 treatment group); F4 (1:2 treatment group); and F5 (2:1 treatment group). The induction was conducted for 14 days, while the treatment was carried out for seven days. All data were analyzed using the Kruskal-Wallis and Mann-Whitney tests. The combination extract of avocado and temulawak rhizome has an anti-hyperlipidemic activity. Giving a combination extract of avocado leaf and temulawak rhizome to all treatment groups significantly reduced total cholesterol levels in mice (p = 0.028). Avocado leaves and temulawak rhizomes have potential antihyperlipidemic activity derived from flavonoids. In this study, the potency of the extract efficacy can be achieved when given in combination.

Association of serum irisin levels with glucose and lipid metabolism among adolescents in Yinchuan City from 2017 to 2020

To explore the relationship between serum irisin levels and glucose and lipid metabolism among adolescents in Yinchuan City. From 2017 to 2020, a conbination of convenient sampling and stratified cluster random sampling method were used to select 1219 adolescents aged 12 to 18 years old in Yinchuan City as research subjects. The height and weight were measured using the height and sitting height meter and the bioelectrical impedance analyzer. Blood indicators such as fasting plasma glucose(FPG), totalcholesterol(TC), triglyceride(TG), low-density lipoprotein cholesterol(LDL-C) and high-density lipoprotein cholesterol(HDL-C) were measured using fully automatic biochemical analyzer. Serum irisin levels were measured by enzyme-linked immunosorbent assay(ELISA). Binary logistic regression was used to analyze the correlation between irisin and abnormal glucose and lipid metabolism. The FPG, TC, HDL-C and LDL-C levels of subjects in the highest tertile of irisin levels were significantly lower than those of subjects in the lowest tertile of irisin levels(F values were 5.13, 3.15, 3.07 and 5.01, P<0.05), and the differences were statistically significant(all P<0.05). The serum irisin levels in the hyperglycemia group(t=2.87, P<0.01), hypercholesterolemia group(t=2.36, P=0.02) and hyperLDL-Cemia group(t=2.34, P=0.02) were significantly lower than those in the normoglycemia group, normal TC group and normal LDL-C group. Meanwhile, the irisin level in the low HDL-Cemia group(t=-2.57, P=0.01) was significantly higher than that in the normal HDL-C group, and the differences were statistically significant(P<0.05). Participants in the highest tertile of irisin had 0.51, 0.49 and 0.50 times the risk of hyperglycemia(OR=0.51, 95%CI 0.29-0.87), hypercholesterolemia(OR=0.49, 95%CI 0.27-0.89) and hyperLDL-cemia(OR=0.50, 95%CI 0.25-0.99) compared with those in the lowest tertile. Low levels of irisin are associated with the occurrence of hyperglycemia, hypercholesterolemia, and hyperLDL-Cemia in adolescents.

Proteomic Signatures of Coronary Artery Disease and Hypercholesterolemia

Background: Coronary artery disease (CAD) is the most common type of cardiovascular disease (CVD), it causes narrowing of the blood vessel lumen due to atherosclerotic plaque formation. Atherosclerosis, is strongly influenced by hypercholesterolemia (HC). Proteomics offers advantages over traditional studies that focus on individual biomarkers. This method provides a holistic view by examining the entire proteomic spectrum in a biological sample, making it an indispensable asset for spotting potential novel protein biomarkers directly linked to atherosclerosis occurrence, progression, and complications such as plaque instability or rupture. Methods: Slow Off-rate Modified Aptamer (SOMAmer)-based protein array was used to quantify proteins. Our cross-sectional study involved healthy controls (n=45), and patients diagnosed with HC (n=51) or CAD (n=32). Proteome data was analyzed using multiple statistical methods. Results: The orthogonal partial least square discriminant analysis (OPLS-DA) revealed a clear separation of the 3 study groups based on two principal components, with R2X= 0.267, R2Y= 0.9, and Q2= 0.28, indicating distinct protein alterations between groups. A total of 1,305 proteins were analyzed and 156 of them in CAD vs control, 140 of them in HC vs control, and 326 of the proteins in CAD vs HC comparisons, were significantly differentially expressed with a p-value<0.05. Among those, q-value<0.05 were determined. As a result, in CAD patients, 2 proteins exhibited significantly differential expressions compared to healthy controls. In contrast, HC patients had 15 significantly altered proteins compared to controls. Furthermore, a comparison between CAD and HC patients revealed 87 significantly regulated proteins. The receiver operating characteristic (ROC) was performed on proteins with distinct expressions ( q<0.05) in pairwise group comparisons. The AUC was calculated to identify potential biomarker candidates for the disease groups. In the CAD vs. control analysis, both significant proteins (PCSK9, SDF-1) exhibited an AUC of 0.75. In the comparison between HC and control groups, out of 15 significantly altered proteins, 7 had an AUC of 0.75 or higher (LRP1B, Apo E, QORL1, Apo E3, Apo B, Transferrin, MMP-3). Among the 87 proteins significantly differentially expressed in CAD versus HC, 59 had an AUC ≥ 0.75. Sixteen of these proteins had an AUC ≥ 0.80. Conclusion: Distinct protein patterns associated with each condition were identified. CAD patients showed a significant increase in the cholesterol-metabolizing protein PCSK9 and varying levels of the angiogenesis-related protein SDF-1. Several other proteins (LRP1B, VAV, CSRP3, HSP 60, and TAK1-TAB1) also exhibited unique expressions in disease groups, suggesting potential roles in atherosclerosis development. Moreover, a statistically significant correlation between SDF-1, ApoB levels, and LDL levels was found in CAD patients but not in healthy controls. This discovery phase cohort study unveils potential biomarkers for atherosclerosis within the HC context. This is the full abstract presented at the American Physiology Summit 2024 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.

Ocular manifestations of severe familial hypercholesterolemia

BackgroundTo study ocular manifestations of patients with severe familial hypercholesterolemia (FH). MethodsIn this population-based case-control study, patients suffering from severe familial hypercholesterolemia from the Lebanese Familial Hypercholesterolemia Registry, along with age and gender-matched healthy controls were recruited. All participants underwent a comprehensive eye examination, and patients underwent fluorescein angiography as well. Logistic regression models were used to identify any association between patients with severe familial hypercholesterolemia and abnormal eye findings, while adjusting for hypertension and pack-year smoking. The main outcome measure of this study was the development of ocular vascular abnormalities. Results28 patients and 28 controls were recruited. Patients with severe familial hypercholesterolemia had significantly greater odds of developing corneal arcus and xanthelasmas than the control group (p < 0.001). Retinal vascular abnormalities (plaques) were exclusively and more significantly present in patients with familial hypercholesterolemia (18 %). Similarly, retinal arteriosclerosis was exclusively and significantly more prevalent in the familial hypercholesterolemia group (p < 0.001, adjusted odds ratio 6.8). Stratification by LDL levels and genotypes did not show any significant change in the prevalence of any ocular finding. ConclusionIn addition to the well-established increase in incidence of corneal arcus and xanthelasmas, severe familial hypercholesterolemia patients have more prevalent retinal vascular abnormalities that include vascular plaques and arteriosclerosis.

Effect of Prebiotic, Probiotic Bacteria and Symbiotic Diets Containing Bacillus Coagulans and Gum Arabic on Lipid Profile in Hypercholesterolemic Rats

Purpose: Hypercholesterolemia is a major problem for many societies as well as for health professionals due to the close association between cardiovascular disease and lipid abnormalities. The current study was conducted to determine the effect of prebiotic, probiotic bacteria and symbiotic diets containing Bacillus Coagulans and Gum Arabic on lipid profile in hypercholesterolemic rats.&#x0D; Methodology: The spore suspension was prepared and Gum Arabic was purchased as the natural product. 35 male albino rats (170 ± 5 g) were fed a cholesterol-supplemented diet to induce hypercholesterolemia. The rats were divided into 5 groups (n = 7). The group 1: basal diet (negative control), and the other four groups were given hypercholesterolemia diet supplemented with 25% lard and 2% cholesterol for six weeks to induce hypercholesterolemia in rats. They were divided as follows: Group 2: (positive control), Group 3: fed a supplemented basal diet with 5% Gum Arabic (prebiotic), Group 4: fed a supplemented basal diet with coagulase spores, and group 5: fed a basal diet supplemented with 5% Gum Arabic and spores per day of B. coagulans (synbiotic).&#x0D; Results: The findings showed a significant increase in the levels of total cholesterol and triacylglycerol (mg/dL) (P&lt;0.05) in (positive control) fed the basic diet (B.D.), compared to (negative control).&#x0D; Unique Contribution to Theory, Practice and Policy: The Anti-Inflammatory Theory and The theory of using prebiotics to lower cholesterol and reduce its absorption. This study indicates that the theory used in the study has been validated. The best results that showed significant differences with the negative control group were achieved in the hypercholesterolemia groups treated with Gum Arabic (GA5%), where the highest mean value was recorded (28.54 ± 3.71 mg/dL), which was close to the negative control (36.33 ± 5.00 mg/dL). As for the groups that took B. coagulans and GA 5% + B. coagulans, a decrease in LDL-c, (VLDL-c), AST and AST levels, and the best result recorded was in the group GA 5% + B.coagulans. Histological examinations also showed that the liver sections in the fifth group showed a normal structure, except for slight degeneration of the liver cells. The best result was in the group of GA 5%+ B. coagulans treatment group compared to the other groups.

Quantified Metabolomics and Lipidomics Profiles Reveal Serum Metabolic Alterations and Distinguished Metabolites of Seven Chronic Metabolic Diseases.

The co-occurrence of multiple chronic metabolic diseases is highly prevalent, posing a huge health threat. Clarifying the metabolic associations between them, as well as identifying metabolites which allow discrimination between diseases, will provide new biological insights into their co-occurrence. Herein, we utilized targeted serum metabolomics and lipidomics covering over 700 metabolites to characterize metabolic alterations and associations related to seven chronic metabolic diseases (obesity, hypertension, hyperuricemia, hyperglycemia, hypercholesterolemia, hypertriglyceridemia, fatty liver) from 1626 participants. We identified 454 metabolites were shared among at least two chronic metabolic diseases, accounting for 73.3% of all 619 significant metabolite-disease associations. We found amino acids, lactic acid, 2-hydroxybutyric acid, triacylglycerols (TGs), and diacylglycerols (DGs) showed connectivity across multiple chronic metabolic diseases. Many carnitines were specifically associated with hyperuricemia. The hypercholesterolemia group showed obvious lipid metabolism disorder. Using logistic regression models, we further identified distinguished metabolites of seven chronic metabolic diseases, which exhibited satisfactory area under curve (AUC) values ranging from 0.848 to 1 in discovery and validation sets. Overall, quantitative metabolome and lipidome data sets revealed widespread and interconnected metabolic disorders among seven chronic metabolic diseases. The distinguished metabolites are useful for diagnosing chronic metabolic diseases and provide a reference value for further clinical intervention and management based on metabolomics strategy.

Ampiang-Dadih-a combination of Indonesian traditional fermented buffalo milk and black glutinous rice-prevents hypercholesterolemia and liver cell degeneration in vivo: A pilot study.

We aimed to evaluate the potential of Ampiang-Dadih (AD), a combination of Indonesian traditional fermented buffalo milk (Dadih) and black glutinous rice flakes (Ampiang) as an anti-hypercholesterolemic agent and to prevent liver-cell degeneration using a rat model. A mixture of black glutinous rice powder (0.3 gm/gm feed) and fermented buffalo milk (3.74/200 gm BW) was prepared to obtain AD. Fifteen adult male Sprague Dawley rats were divided into three groups of five animals each: (A) negative control group (distilled water; 5 weeks), (B) hypercholesterolemia group (1% cholesterol per feed; 5 weeks), and (C) preventive AD group (1% cholesterol and AD; 5 weeks). The blood lipid profiles were measured at weeks 2, 4, and 5. The liver enzyme activity, cholesterol level, and histology were observed at the end of week 5. AD administration simultaneously with cholesterol in Group C significantly prevented an increase in total plasma cholesterol and low-density lipoprotein levels compared to Group B. Alanine transaminase and aspartate transaminase were maintained at normal levels in Group C. Furthermore, the levels of liver cholesterol and liver cell degeneration in Group C were also maintained because of AD administration compared to that in Group B. This study demonstrated that AD has the potential to be developed as a functional food for hypercholesterolemia prevention.

#248 : Maternal Hypercholesterolemia Would Increase the Incidence of Embryo Aneuploidy in Couples with Recurrent Implantation Failure

Background and Aims: The association of dyslipidemia with reproductive outcomes is largely unknown, especially in recurrent implantation failure (RIF) patients. This study aimed to explore the impact of abnormal blood lipid levels on embryo genetic status and pregnancy outcomes in unexplained RIF (uRIF) patients after preimplantation genetic testing for aneuploidy (PGT-A). Method: In this retrospective study, they were divided into 4 groups according to the levels of cholesterol and triglyceride: non-hyperlipidemia group (NonH group), simple hypercholesterolemia group (SHC group), simple hypertriglyceridemia group (SHC group) and mixed hyperlipidemia group (MixH group). Additionally, patients were divided into 2 groups according to their HDL-C level. Embryos’ genetic status and pregnancy outcomes after transfer of euploid embryos were analyzed. Binary logistic regression and/or generalized estimating equation model were conducted to investigate the association of different types of dyslipidemia with aneuploid embryo rate and cumulative live-birth rate. Results: A total of 474 women were divided into four groups: NonH group (N=349), SHC group (N=55), SHT group (N=52) and MixH group (N=18). Compared with the NonH group, SHC group had a significantly increased aneuploid embryo rate [48.3% vs. 36.7%, P=0.006; adjusted OR (95% CI) = 1.52(1.04-2.22)], as well as a reduced number of good-quality blastocysts [3.00±2.29 vs. 3.74±2.77, P=0.033]. The SHC group showed a lower cumulative live-birth rate (47.0% vs. 40.0%), good birth outcome (37.2% vs. 34.5%) and a higher risk of clinical pregnancy loss (11.1% vs. 17.9%) but did not reach statistical significance. The incidences of obstetric or neonatal complications and other adverse events were similar in the four groups. Conclusion: We found that uRIF women with hypercholesterolemia had an increased proportion of aneuploid embryos and a reduced number of high-quality embryos, while different types of hyperlipidemias had no correlation with cumulative live birth rate as well as pregnancy and neonatal outcomes.

Alterations of ileal mucosa-associated microbiota in hypercholesterolemia patients

Many metabolic diseases have been demonstrated to be associated with changes in the microbiome. However, no studies have yet been conducted to examine the characteristics of the mucosal microbiota of patients with hypercholesterolemia. We aimed to examine mucosa-associated microbiota in subjects with hypercholesterolemia. We conducted a case-control study, in which ileal mucosal samples were collected from 13 hypercholesterolemia patients and 13 controls for 16S rRNA gene sequencing. There were differences in the composition of ileal mucosal microbiota based on beta diversity between the hypercholesterolemia and control groups (P < 0.05). Compared with the control group, the phylum Bacteroidetes and the genera Bacteroides, Butyricicoccus, Parasutterella, Candidatus_Soleaferrea, and norank_f__norank_o__Izemoplasmatales were less abundant in the hypercholesterolemia group (P < 0.05), while the genus Anaerovibrio was enriched in the hypercholesterolemia group (P < 0.05). The relative abundance of Bacteroides was negatively correlated with total cholesterol and low-density lipoprotein cholesterol (P < 0.01). The relative abundance of Coprococcus was negatively correlated with triglycerides and body mass index (all P < 0.05). PICRUSt functional prediction analysis showed that pathways related to Glycerophospholipid metabolism, ABC transporters, Phosphotransferase system, and Biofilm formation - Escherichia coli, and infectious diseases of pathogenic Escherichia coli were enriched in the hypercholesterolemia group. This work suggests a potential role of ileal mucosal microbiota in the development of hypercholesterolemia.

Maternal hypercholesterolemia would increase the incidence of embryo aneuploidy in couples with recurrent implantation failure

BackgroundThe association of dyslipidemia with embryo development and pregnancy outcomes is largely unknown, especially in unexplained recurrent implantation failure (uRIF) patients. Here, this study aimed to explore the impact of abnormal blood lipid levels on embryo genetic status and pregnancy outcomes after preimplantation genetic testing for aneuploidy (PGT-A) from a clinical perspective.MethodsThis study retrospectively analyzed 502 patients diagnosed as uRIF. They were divided into four groups according to the levels of cholesterol and triglyceride: nonhyperlipidemia group (NonH group), simple hypercholesterolemia group (SHC group), simple hypertriglyceridemia group (SHC group) and mixed hyperlipidemia group (MixH group). At the same time, patients were divided into non-low HDL-C group and low HDL-C group according to their HDL-C level. The outcomes of embryos genetic testing and pregnancy outcomes after PGT-A was analyzed between groups. Binary logistic regression and/or generalized estimating equation (GEE) model were conducted to investigate the association of different types of dyslipidemia with embryonic aneuploidy rate and cumulative live-birth rate.Results474 women who met the inclusion criteria were divided into four groups: NonH group (N = 349), SHC group (N = 55), SHT group (N = 52) and MixH group (N = 18). Compared with the NonH group, SHC group had a significantly increased rate of embryo aneuploidy [48.3% vs. 36.7%, P = 0.006; adjusted OR (95% confidence interval) = 1.52(1.04–2.22), P = 0.029], as well as a reduced number of good-quality embryos on day 5 or 6 [3.00 ± 2.29 vs. 3.74 ± 2.77, P = 0.033]. The SHC group showed a tendency of a lower cumulative live birth rate (47.0% vs. 40.0%), a lower incidence of good birth outcome (37.2% vs. 34.5%) and a higher risk of clinical pregnancy loss (11.1% vs. 17.9%), but did not reach statistical significance (P > 0.05). The incidences of obstetric or neonatal complications and other adverse events were similar in the four groups. Whether patients have low HDL-C did not differ in pregnancy outcomes.ConclusionsWe found that uRIF women with hypercholesterolemia had an increased proportion of aneuploid embryos and a reduced proportion of high-quality embryos, while different types of hyperlipidemia had no correlation with cumulative live birth rate as well as pregnancy and neonatal outcomes.

Carob Extract (Ceratonia siliqua L.): Effects on Dyslipidemia and Obesity in a High-Fat Diet-Fed Rat Model.

Dyslipidemia and obesity are recognized as two of the major global health issues and main risk factors for coronary heart disease and cerebrovascular disease. In recent years, carob has shown certain antioxidant and anti-dyslipidemic potential. In this study, Wistar rats were fed with a standard and cholesterol-enriched diet and treated orally with carob extract and simvastatin for four weeks. After sacrifice, blood samples were collected for biochemical analysis, and liver tissue was taken for histological and immunohistochemical assessment. Weight gain was significantly higher in groups fed with cholesterol-fortified granules; total cholesterol was found to be significantly lower in the hypercholesterolemic groups treated with simvastatin and simvastatin/carob combined regimens compared with hypercholesterolemic animals treated with saline (p < 0.05). The same was true for low-density lipoprotein cholesterol and the LDL/HDL ratio (p < 0.05). Adiponectin was remarkably higher in animals treated with simvastatin compared to all other groups (p < 0.05). Leptin was significantly lower in groups treated with carob and simvastatin compared to the hypercholesterolemic group treated with saline (p < 0.05). Carob/simvastatin co-administration reduced hepatocyte damage and improved liver morphology. A study confirmed the anti-dyslipidemic, anti-obesity, and hepatoprotective potential of carob pulp alone or in combination with simvastatin in the treatment of high-fat diet-fed rats.

Effect of leaf extract of Terminalia catappa on haematological profile in poloxamer induced hypercholesterolemia in Wistar rats

This research was aimed at assessing the effect of the administration of ethanol extract of Terminalia catappa, on haematological indices following poloxamer induced hypercholesterolemia in male Wistar rats. Thirty- five (35) Wistar male rats were allowed to acclimatize for a period of 7 days, in a well-ventilated room at room temperature and relative humidity of 29°C and 70% respectively with 12 hours natural light-dark cycle. They were allowed food and water ad libitum. Good hygiene was maintained by daily cleaning and removal of faeces and spills from their cages. The rats were randomly divided into 5 groups of 7 rats each. Group A: were fed with standard chow and distilled water (NC). Group B: were induced with 1.0mg/kg dose of P-407 without treatment (HC). Group C: were induced with 1.0 mg/kg dose of P-407 and treated with atorvastatin (ATV) at 20mg/kg body weight/day Group D: were induced with 1.0mg/kg dose of P-407 and treated with leaves extract (HLE) at 100mg/kg body weight/day Group E: were induced with 1.0mg/kg dose of P-407 and treated with leaf extract (HLE) at 200mg/kg body weight/ day. The dose regimens were administered once daily for 14 days. The rats were monitored for clinical signs and death. The result reveals that there was a significant (P&lt;0.05) increase in RBC, Hb and WBC when compared to the normal, standard and hypercholesterolemic group in the group treated with T. catappa ethanol extract. Similarly, there was a significant (P&lt;0.05) decrease in PCV when compared with the normal, standard and hypercholesterolemic control. On the other hand, the extract produced no significant(P&lt;0.05) difference in serum MCV, MCH and MCHC, neutrophil, platelet and lymphocytes when compared with the normal, standard and hypercholesterolemic control.It can be inferred from this present research work that T.catappa contains some phytochemical, and/or neutraceuticals with haematopoietic and immunomodulatory effect which may trigger or boost the defense system against invasion by either pathogens or pathogenic organisms in poloxamer induced hypercholesterolemic rats.

Therapeutic Aspects of Prunus cerasus Extract in a Rabbit Model of Atherosclerosis-Associated Diastolic Dysfunction.

This study evaluates the potential therapeutic effects of anthocyanin-rich Prunus cerasus (sour cherry) extract (PCE) on atherosclerosis-associated cardiac dysfunction, described by the impairment of the NO-PKG (nitric oxide-protein kinase G) pathway and the antioxidant capacity. Initially, a rabbit model of atherosclerotic cardiovascular disease was established by administering a cholesterol-rich diet, enabling the examination of the impact of 9 g/kg PCE on the pre-existing compromised cardiovascular condition. After that, the animals were divided into four groups for 12 weeks: the (1) untreated control group; (2) PCE-administered healthy rabbits; (3) hypercholesterolemic (HC) group kept on an atherogenic diet; and (4) PCE-treated HC group. Dyslipidemia, impaired endothelial function, and signs of diastolic dysfunction were evident in hypercholesterolemic rabbits, accompanied by a reduced cardiac expression of eNOS (endothelial nitric oxide synthase), PKG, and SERCA2a (sarco/endoplasmic reticulum calcium ATPase 2a). Subsequent PCE treatment improved the lipid profile and the cardiac function. Additionally, PCE administration was associated with elevated myocardial levels of eNOS, PKG, and SERCA2a, while no significant changes in the vascular status were observed. Western blot analysis further revealed hypercholesterolemia-induced increase and PCE-associated reduction in heme oxygenase-1 expression. The observed effects of anthocyanins indicate their potential as a valuable addition to the treatment regimen for atherosclerosis-associated cardiac dysfunction.

Heavy Ion Irradiation Reduces Vulnerability to Atrial Tachyarrhythmias - Gap Junction and Sympathetic Neural Remodeling.

Low-invasive stereotactic body radiation therapy is a novel anti-arrhythmic strategy. The mechanisms underlying its effects against ventricular tachycardia/fibrillation (VT/VF) are gradually becoming clear, whereas those underlying atrial tachycardia/fibrillation (AT/AF) remain unknown. This study investigated the effects of carbon ion beam on gap junction expression and sympathetic innervation.Methods and Results: Atrial and ventricular tachyarrhythmia models was established in 26 hypercholesterolemic (HC) 3-year-old New Zealand white rabbits; 12 rabbits were irradiated with a single 15-Gy carbon ion beam (targeted heavy ion irradiation [THIR]) and 14 were not (HC group). Eight 3-month-old rabbits (Young) were used as a reference group. In vivo induction frequencies in the Young, HC, and HC+THIR groups were 0%, 9.9%, and 1.2%, respectively, for AT/AF and 0%, 7.8%, and 1.2%, respectively, for VT/VF (P<0.01). The conduction velocity of the atria and ventricles on optical mapping was significantly reduced in the HC group; this was reversed in the HC+THIR group. Connexin-40 immunolabelling in the atria was 66.1-78.7% lower in the HC than Young group; this downregulation was less pronounced in the HC+THIR group (by 23.1-44.4%; P<0.01). Similar results were obtained for ventricular connexin-43. Sympathetic nerve densities in the atria and ventricles increased by 41.9-65.3% in the HC vs. Young group; this increase was reversed in the HC+THIR group. Heavy ion radiation reduced vulnerability to AT/AF and VT/VF in HC elderly rabbits and improved cardiac conductivity. The results suggest involvement of connexin-40/43 upregulation and suppression of sympathetic nerve sprouting.

Intratumoral Restoration of miR-137 Plus Cholesterol Favors Homeostasis of the miR-137/Coactivator p160/AR Axis and Negatively Modulates Tumor Progression in Advanced Prostate Cancer.

MicroRNAs (miRNAs) have gained a prominent role as biomarkers in prostate cancer (PCa). Our study aimed to evaluate the potential suppressive effect of miR-137 in a model of advanced PCa with and without diet-induced hypercholesterolemia. In vitro, PC-3 cells were treated with 50 pmol of mimic miR-137 for 24 h, and gene and protein expression levels of SRC-1, SRC-2, SRC-3, and AR were evaluated by qPCR and immunofluorescence. We also assessed migration rate, invasion, colony-forming ability, and flow cytometry assays (apoptosis and cell cycle) after 24 h of miRNA treatment. For in vivo experiments, 16 male NOD/SCID mice were used to evaluate the effect of restoring miR-137 expression together with cholesterol. The animals were fed a standard (SD) or hypercholesterolemic (HCOL) diet for 21 days. After this, we xenografted PC-3 LUC-MC6 cells into their subcutaneous tissue. Tumor volume and bioluminescence intensity were measured weekly. After the tumors reached 50 mm3, we started intratumor treatments with a miR-137 mimic, at a dose of 6 μg weekly for four weeks. Ultimately, the animals were killed, and the xenografts were resected and analyzed for gene and protein expression. The animals' serum was collected to evaluate the lipid profile. The in vitro results showed that miR-137 could inhibit the transcription and translation of the p160 family, SRC-1, SRC-2, and SRC-3, and indirectly reduce the expression of AR. After these analyses, it was determined that increased miR-137 inhibits cell migration and invasion and impacts reduced proliferation and increased apoptosis rates. The in vivo results demonstrated that tumor growth was arrested after the intratumoral restoration of miR-137, and proliferation levels were reduced in the SD and HCOL groups. Interestingly, the tumor growth retention response was more significant in the HCOL group. We conclude that miR-137 is a potential therapeutic miRNA that, in association with androgen precursors, can restore and reinstate the AR-mediated axis of transcription and transactivation of androgenic pathway homeostasis. Further studies involving the miR-137/coregulator/AR/cholesterol axis should be conducted to evaluate this miR in a clinical context.

Obesity and Its Association with Undiagnosed Diabetes Mellitus, High Blood Pressure and Hypercholesterolemia in the Malaysian Adult Population: A National Cross-Sectional Study Using NHMS Data.

This study aimed to report the prevalence of obesity, classified using Asian cut-off, and its relationships with undiagnosed diabetes mellitus, high blood pressure, and hypercholesteremia. We analyzed the nationally representative data from 14,025 Malaysian adults who participated in the NHMS 2015. The relationship between obesity and undiagnosed diabetes mellitus, high blood pressure, and hypercholesteremia was determined using multivariable logistic regressions, and lifestyle risk factors and sociodemographic characteristics were adjusted. The undiagnosed high blood pressure group showed the highest proportionate of overweight/obese (80.0%, 95% CI: 78.1-81.8) and central obesity (61.8%, 95% CI: 59.3-64.2). Inverse association was observed between underweight with undiagnosed high blood pressure (aOR: 0.40, 95% CI: 0.26-0.61) and hypercholesterolemia (aOR: 0.75, 95% CI: 0.59-0.95) groups. In contrast, positive relationships were shown between overweight/obese and risk of undiagnosed diabetes mellitus (aOR: 1.65, 95% CI: 1.31-2.07), high blood pressure (aOR: 3.08, 95% CI: 2.60-3.63), and hypercholesterolemia (aOR: 1.37, 95% CI: 1.22-1.53). Likewise, central obesity was positively associated with a risk of undiagnosed diabetes mellitus (aOR: 1.40, 95% CI: 1.17-1.67), high blood pressure (aOR: 2.83, 95% CI: 2.45-3.26), and hypercholesterolemia (aOR: 1.26, 95% CI: 1.12-1.42). Our findings indicated the importance of periodical health examinations to assess the risk of non-communicable diseases among the general and abdominal obese Malaysian adults.

Apigenin ameliorates hypercholesterolemic-induced kidney injury via modulating renal KIM-1, Fn1, and Nrf2 signaling pathways.

Hypercholesterolemia (HC) is a devastating metabolic disorder that has a negative effect on the kidneys' functional and structural modalities via oxidative stress and inflammation. The aim of this paper is to elaborate on the role of the flavonoid apigenin (Apg), considering its antioxidant, anti-inflammatory, and antiapoptotic capabilities, in alleviating hypercholesterolemic-induced kidney injury. Twenty-four adult Wister male rats were allocated into four equal groups and treated for eight consecutive weeks: a control group, supplemented with a normal pellet diet (NPD); the Apg group, supplemented with NPD and Apg (50 mg/Kg); the HC group, fed with NPD enriched with 4% cholesterol and 2% sodium cholate; and the HC/Apg group, concomitantly rendered hypercholesterolemic and gavaged with Apg. At the end of the experiment, serum samples were collected to measure renal function parameters, lipid profile, MDA, and GPX-1. Thereafter, the kidneys were processed for histological study and homogenized to assess IL-1β, IL-10, and the gene expression of kidney injury molecule-1 (KIM-1), fibronectin 1 (Fn1), and NF-E2-related factor 2 (Nrf2) via RT-qPCR. HC disturbed the renal function, lipid profile, and serum redox balance. In addition, HC elicited a proinflammatory/anti-inflammatory imbalance, upregulating KIM-1 and Fn1 and downregulating the Nrf2 gene expression of the kidney tissue. Moreover, HC induced marked histopathological changes in the kidney cytoarchitecture. Efficaciously, upon concomitant Apg supplementation with a high-cholesterol diet, most functional, histological, and biomolecular impairments of the kidney were comparatively restored in the HC/Apg group. Apg mitigated HC-induced kidney injury via modulating the KIM-1, Fn1, and Nrf2 signaling pathways, a promising effect that may be useful as an adjunct to antihypercholesterolemic medications to treat the devastating renal complications of HC.

Clinicopathological Characteristics and Outcomes of Immunoglobulin A Nephropathy with Different Types of Dyslipidemia: A Retrospective Single-Center Study

Introduction: Immunoglobulin A nephropathy (IgAN) is one of the most common glomerulonephritic diseases in the world. Several lines of evidence have suggested that dyslipidemia is related to the disease progression and prognosis of IgAN. However, the study is scarce on the clinicopathological characteristics and outcomes of IgAN with dyslipidemia. Methods: This study retrospectively analyzed 234 patients with biopsy-proven idiopathic IgAN at the Department of Nephrology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, between January 2015 and June 2021. The participants were divided into dyslipidemia (n = 119) and non-dyslipidemia (n = 115), and the dyslipidemia group was also divided into the following 4 groups: hypertriglyceridemia group, hypercholesterolemia group, mixed hyperlipidemia group, and low high-density lipoprotein cholesterol group. The estimated glomerular filtration rate (eGFR) was estimated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Results: The prevalence of dyslipidemia in IgAN patients in our center was 50.9% (119/234). The patients with dyslipidemia presented with higher systolic blood pressure (BP), diastolic BP, serum creatinine, uric acid, hemoglobin, proteinuria, and eGFR (p < 0.05). Proportions of males, hypertension, and chronic kidney disease stage 2∼5 were also higher in the dyslipidemia group (p < 0.05). Similarly, the pathological characteristics performed were worse in the dyslipidemia group. Most dyslipidemia patients had a higher percentage of mesangial hypercellularity (M1) and tubular atrophy/interstitial fibrosis (T1∼2) in the Oxford Classification’s scoring system (p < 0.05). Multivariate logistic regression analysis revealed that male gender (odds ratio [OR] = 2.397, 95% confidence interval [CI]: 1.051–5.469, p = 0.038) and proteinuria (OR = 1.000, 95% CI: 1.000–1.001, p = 0.035) were possible risk factors for dyslipidemia. A total of 13 patients (13.8%) in the dyslipidemia group had an endpoint event, of which 6 patients (6.4%) had a ≥50% decrease in eGFR from baseline and 7 patients (7.4%) reached the end-stage renal disease stage. Kaplan-Meier survival curve analysis showed that patients in the dyslipidemia group had a worse outcome than those in the non-dyslipidemia group (log-rank test, p = 0.048). Conclusions: IgAN patients with dyslipidemia presented more severe clinicopathological characteristics. Male gender and proteinuria are significantly associated with the occurrence of dyslipidemia in IgAN patients. Patients in the dyslipidemia group had a worse prognosis than those in the non-dyslipidemia group, which may be essential for the disease management of IgAN and help identify the high-risk patients.

Effect of Linoleic Acid on Cholesterol Levels in a High-Fat Diet-Induced Hypercholesterolemia Rat Model.

Cardiovascular disease is the leading cause of morbidity and mortality worldwide, accounting for almost one-third of all deaths. The risk factors for developing this disease include high levels of serum total cholesterol (TC), triglycerides (TG), and low-density lipoprotein (LDL), alongside low levels of high-density lipoprotein (HDL). Dietary linoleic acid has been suggested to reduce these risk factors. This study aims to determine the effects of linoleic acid on cholesterol levels, liver function tests, and structural changes in liver tissue in comparison with fenofibrate in a hypercholesterolemic rat model. Thirty-six male Sprague Dawley rats (150-180 g) were divided into non-hypercholesterolemic and hypercholesterolemic groups. Hypercholesterolemia was induced in the rats by feeding them with a high-fat diet for two weeks. After two weeks, the non-hypercholesterolemic and hypercholesterolemic rats were equally divided into six groups (n = 6): control non-hypercholesterolemic rats, non-hypercholesterolemic rats treated with fenofibrate (60 mg/kg), non-hypercholesterolemic rats treated with linoleic acid (5 mg/kg), control hypercholesterolemic rats, hypercholesterolemic rats treated with fenofibrate (60 mg/kg), and hypercholesterolemic rats treated with linoleic acid (5 mg/kg). The changes in the rats' body weight, serum lipid profiles, atherogenic indices, and liver function test results were obtained. The rats' liver tissues were stained for histopathological analysis. The linoleic acid-treated hypercholesterolemic rats exhibited significantly reduced serum TC, TG, LDL, aspartate aminotransferase, and alanine aminotransferase levels, as well as increased HDL levels compared with the control hypercholesterolemic rats. These linoleic acid effects were comparable to those in the fenofibrate-treated hypercholesterolemic rats. In conclusion, linoleic acid possesses early anti-hypercholesterolemic properties, which may be due to the reductions in serum cholesterol levels and mild early structural changes in the liver tissues of hypercholesterolemic rats. Therefore, continued studies on linoleic acid in atherosclerotic and/or obese animal models are suggested.

Cholesterol Triggers Nuclear Co-Association of Androgen Receptor, p160 Steroid Coactivators, and p300/CBP-Associated Factor Leading to Androgenic Axis Transactivation in Castration-Resistant Prostate Cancer.

Cholesterol modulates intratumoral androgenic signaling in prostate cancer; however, the molecular mechanisms underlying these changes in castration-resistant prostate cancer (CRPC) are not fully elucidated. Herein, we investigated the effect of cholesterol on androgen receptor (AR) coactivators expression and tumorigenesis in vitro and in vivo. Herein, we monitored the expression of AR coactivators (SRC-1, 2, 3 and PCAF) genes in PC-3 cells exposed to 2µg/mL of cholesterol for 8 hours by qPCR. We also performed cell migration at 0, 8, 24, 48 and 72h and flow cytometry assays (viability, apoptosis, and cell cycle) after a 24h exposure. Immunofluorescence assay was performed to evaluate the protein expression of the AR coactivators. Additionally, in vivo experiments were conducted using 22 male NOD/SCID mice. Mice were fed a standard (Control) or hypercholesterolemic (HCOL) diet for 21 days and then subcutaneously implanted with PC-3 cells. The tumor volume was calculated every two days, and after four weeks, the tumors were resected, weighed, and the serum lipid profile was measured. We also measured the intratumoral lipid profile and AR coactivators gene and protein expression by qPCR and Western Blot, respectively. Intratumor testosterone and dihydrotestosterone (DHT) concentrations were determined using ELISA. Cholesterol up-regulated the gene expression of coactivators SRC-1, SRC-2, SRC-3 and PCAF, increasing AR expression in PC-3 cells. Next, cholesterol-supplemented PC-3 cells exhibited increased cell migration and altered cell cycle phases, leading to changes in proliferation and reduced apoptosis. We found that SRC-1, SRC-2, SRC-3 and PCAF proteins co-localized in the nucleus of cholesterol-supplemented cells and co-associate with AR. In the in vivo model, the hypercholesterolemic (HCOL) group displayed higher serum total and intratumoral cholesterol levels, increased testosterone and dihydrotestosterone concentrations, and up-regulated AR coactivator expression. The tumor volume of the HCOL group was significantly higher than the control group. Our findings revealed that increased nuclear translocation of the coactivators leads to up-regulated AR gene and protein expression, potentially influencing tumor progression. Studies targeting cholesterol-modulated changes in AR coactivator expression may provide insights into the molecular mechanisms associated with the CRPC phenotype.