Hyperlipidemia Research Articles

Buerger Disease: Pathological Changes in Elderly Patients.

Reports of vascular lesion changes in elderly Buerger disease patients are rare. Patients are expected to continue to have typical Buerger disease even after the age of 50. However, after 50, when patients suffer from atherosclerotic risk factors, such as hypertension, diabetes mellitus, or hyperlipidemia, what kind of changes will occur? We will report on 3 cases of hypertension, diabetes mellitus, or hyper lipidemia after or around 50 years of age. As a result, atherosclerosis was present in the iliac or aortic regions in the remaining thromboangiitis lesions below the groin area. (This is secondary publication from the J Jpn Coll Angiol 2021; 61: 107–113.)

Hypertriglyceridemia-Induced Pancreatitis and a Lipemic Blood Sample: A Case Report and Brief Clinical Review

Hypertriglyceridemia is the third most common cause of acute pancreatitis after gallstones and long-term alcohol use. There are specific therapeutic options unique to hyperglyceridemia-induced pancreatitis, such as continuous insulin therapy and plasmapheresis, emphasizing the importance of identifying hypertriglyceridemia as the cause. Triglyceride levels > 1000 mg/dL may result in a visibly lipemic blood sample. Lipemic samples may interfere with laboratory equipment, resulting in erroneous levels or the inability to measure several serum blood tests. Consider hypertriglyceridemia as a cause for acute pancreatitis in the setting of a lipemic blood sample or when gallstones have been excluded.

Value of Genetic Testing for Lipoprotein(a) Variants

Value of Genetic Testing for Lipoprotein(a) Variants

Atorvastatin Decreases Renal Calcium Oxalate Stone Deposits by Enhancing Renal Osteopontin Expression in Hyperoxaluric Stone-Forming Rats Fed a High-Fat Diet.

Calcium oxalate (CaOx) is the major constituent of kidney stones. Growing evidence shows a close connection between hyperlipidemia, cardiovascular disease (CVD), and the formation of kidney stones. Owing to their antioxidant properties, statins control hyperlipidemia and may ameliorate CaOx stone formation. The present study was designed to investigate the suppressive effects of statins on CaOx urolithiasis and their potential mechanism. We used rats fed a high-fat diet (HFD) to achieve hyperlipidemia (HL) and hydroxyproline (HP) water to establish a hyperoxaluric CaOx nephrolithiasis model; the animals were administered statins (A) for 28 days. The rats were divided into eight groups treated or not with A, i.e., Control, HP, HL, HL + HP. HL aggravated urinary calcium crystallization compared to the control. Due to increased expression of renal osteopontin (OPN), a key anti-lithic protein, and reduced free radical production, the calcium crystals in the urinary bladder increased as renal calcium deposition decreased. The levels of the ion activity product of CaOx (AP(CaOx)) decreased after statins administration, and AP(Calcium phosphate) (CaP) increased, which suggested the dominant calcium crystal composition changed from CaOx to CaP after statin administration. In conclusion, atorvastatin decreases renal CaOx stone deposits by restoring OPN expression in hyperoxaluric rats fed a HFD.

High levels of FBS and HbA1c and their association with diabetic retinopathy: a study in the north of Iran.

Diabetic retinopathy, which is a common complication of diabetes, is one of the most common reasons of blindness in adults. There are several potential risk factors for diabetic retinopathy such as hypertension (HTN), hyperlipidemia (HLP), high fasting blood sugar (FBS), and high Hemoglobin A1c (HbA1c). Yet, ethnicity is another factor which may contribute to diabetic retinopathy regardless of the potential risk factors mentioned. The aim of this study, therefore, is to find the risk factors associated with diabetic retinopathy in the north of Iran. This was a retrospective cohort study including a total of 1,125 patients divided into three groups as follows: (i) patients with no diabetic retinopathy (NDR group; n = 398); (ii) patients with non-proliferative diabetic retinopathy (non-PDR group; n = 408); (iii) patients with proliferative diabetic retinopathy (PDR group; n = 319). The laboratory data were collected from patients for analysis. Diabetic patients with retinopathy had significantly higher levels of FBS compared with those without retinopathy (p = 0.001). Patients with PDR or non-PDR had higher levels of HbA1c compared with patients without retinopathy (p = 0.001). In contrast, no association was observed between HTN or HLP and diabetic retinopathy. On the other hand, duration of diabetes was another important factor affecting diabetic retinopathy. Higher levels of FBS and HbA1c were observed in patients with diabetic retinopathy. Monitoring and controlling of FBS and HbA1c of diabetic patients could prevent the occurrence of diabetic retinopathy.

An unusual case of familial hyperlipidemia with statin induced rhabdomyolysis

Familial hypercholesterolemia (FH), also known as Type 2 familial dyslipidemia is a genetic disorder characterized by high levels of low-density lipoprotein (LDL) cholesterol in the blood. Elevated LDL cholesterol levels leads to ischemic heart disease in younger age group. FH is well known to cause deposition of cholesterol in muscle tendons causing tendon xanthomas which present as nodules over Achilles' tendon. Familial hypercholesterolemia is treated with high dose of statins to bring down the LDL cholesterol. We hereby report an unusual case of familial hypercholesterolemia with very high LDL levels (504 mg/dl) and tendon xanthomas who developed statin induced rhabdomyolysis due to consumption of high doses of statins. Patient had consumed both atorvastatin and rosuvastatin by mistake which led to rhabdomyolysis. A clinician must look out for this complication in any patient who is started on high dose of statins. Anticipation of this complication, patient education and periodic checking of muscle enzyme creatine phosphokinase (CPK) and serum creatinine in a patient on high dose statins helps in tackling this complication effectively.

Pre-Diagnosis Aspirin Use Has No Effect on Overall Survival in Patients With Colorectal Cancer: A Study of a Multi-Racial Population.

IntroductionAspirin has been associated with a reduction in mortality in patients diagnosed with colorectal cancer (CRC). A possible mechanism for this is related to the programmed cell death 1 (PD-1) immune checkpoint pathway. Aspirin may have a synergistic effect with PD-1 inhibitors via inhibition of prostaglandin E2 (PGE2) production, which can reverse the ability of tumor cells to evade the immune system. This appears to be strongest in cancers that express PI3 kinase (PI3K) signaling activity, which aspirin downregulates. However, the benefit of pre-diagnosis aspirin use on CRC overall survival (OS) and cancer-specific survival is still controversial, and most studies have been performed in racially homogenous populations. Our study examines the effect of pre-diagnosis aspirin therapy on OS in a racially diverse group of patients with CRC.MethodsThis is a retrospective chart review of 782 patients diagnosed with CRC from January 2007 to December 2020. Kaplan-Meier curve was created to study the association of aspirin exposure compared to no exposure on OS. In addition, univariate and multivariate binary logistic regression analyses were done to investigate potential predictors of survival.ResultsOf the 782 patients with CRC, 55.1% were males, 22.2% whites, 58.5% Asians, and 17.7% Pacific-Islanders. Moreover, 38.4% of the patients had a history of aspirin use, 79% of them used it for more than one year. There were more patients with hypertension (HTN), hyperlipidemia (HLD), diabetes mellitus (DM), and chronic kidney disease (CKD) among those with a history of aspirin use. There was no difference in one, three, and five-year OS among aspirin users compared to non-users, p-value = 0.63. Age, grade, and stage were potential predictors of worsened OS. However, treatment with chemotherapy and CKD were potential predictors of worsened OS on univariate analysis only. No significant association was noticed with gender, tumor location, or other associated comorbidities.ConclusionThe effect of pre-diagnosis aspirin use on CRC survival is not clear. In this retrospective analysis of a racially diverse population of CRC patients, we found that aspirin use was not associated with improved OS. Therefore, physicians should be careful about using aspirin as adjuvant therapy in CRC patients until high-quality prospective data are available, given the potential associated complications.

Atheroprotective mechanism by which folic acid regulates monocyte subsets and function through DNA methylation

BackgroundRecent studies have suggested that folic acid can restore abnormal DNA methylation and monocyte subset shifts caused by hyperhomocysteinemia (HHcy) and hyperlipidemia (HL). However, the exact mechanism of action is still not fully understood. In this study, we further investigated the reversal effect and underlying mechanism of folic acid on the shift in monocyte subsets induced by aberrant lipids and Hcy metabolism via DNA methylation in vitro and in vivo.ResultsOur results showed that intermediate monocytes were significantly increased but had the lowest global 5-methylcytosine (5-mC) levels in coronary artery disease (CAD) patients, which might lead to a decrease in the global 5-mC levels of peripheral blood leukocytes (PBLs). We also discovered that ARID5B might mediate the increased proportion of intermediate monocytes, as this factor was related to the proportion of monocyte subsets and the expression of CCR2. The expression of ARID5B was inversely associated with the hypermethylated cg25953130 CpG site, which was induced by HL and HHcy. ARID5B could also regulate monocyte CCR2, MCP-1, and TNF-α expression, adhesion and migration, macrophage polarization, and monocyte/macrophage apoptosis, which might explain the regulatory effect of ARID5B on monocyte subset shifting. Folic acid reversed HL- and HHcy-mediated aberrant global and cg25953130 DNA methylation, reduced the proportion of intermediate monocytes, and inhibited the formation of atherosclerotic plaques.ConclusionFolic acid plays a protective role against atherosclerosis through the regulation of DNA methylation, ARID5B expression, and monocyte subsets.

The Correlation of Lipid Peroxidation and Antioxidant Capacity on Perioperative Outcomes in On-Pump CABG in Adults.

Background: Cardiac surgeries in adults usually use cardiopulmonary bypass (CPB) for cardiac protection and provide a blood-free field for operation. However, due to changes in tissue perfusion and ischemia-reperfusion injury (IRI), there are some side effects for CPB operations. Lipid peroxidation and compromised antioxidant defense are consequences of IRI. This can, in turn, cause organ dysfunction and lead to unwanted biochemical and clinical changes. Methods: In a cross-sectional study 107 patients with the ages of 35 to 79 years old matching the inclusion criteria with indication for elective on-pump CABG were studied. Renal function, serum malondialdehyde (MDA) and total antioxidant capacity (TAC), and clinical outcomes were studied until 24 hours after intensive care unit (ICU) admission. Correlations between MDA and TAC and other outcomes were tested. Between-group comparisons was one-way ANOVA with repeated measures was used for inferring changes in the plasma TAC and MDA levels, creatinine, and BUN over time. Correlations were investigated using regression models. Results: Preoperative EF was inversely correlated with TAC at post- CPB time (r= -0.262, p= 0.031). Hyperlipidemia (HLP) was directly associated with higher MDA at post- CPB time (r= 0.267, p= 0.017. Cross-clamp and CPB duration were inversely correlated with the systemic MDA concentration at 24 hours post-ICU admission (r= -0.314, p= 0.005 and r= -0.312, p= 0.005, respectively). Preoperative TAC was inversely correlated with lactate at ICU admission (r= -0.294, p= 0.011). Creatine phosphokinase (CPK) and TAC were directly correlated with post-CPB time (r= -0.327, p= 0.006). Conclusion: According to the findings, a direct correlation between TAC and myocardial protection during CPB exists. Reduced TAC during CPB is associated with elevation of muscle damage marker CPK. Preoperative HLP is associated with higher circulatory MDA content at the post-CPB time.

Sex Differences in the Use of Cardiovascular Drugs: A Survey of Patients in a Single Center.

Patients and medical professionals have a common misconception that cardiovascular diseases (CVD) predominantly affect men, which can lead to less prescribing of cardiovascular drugs to women. This study examined whether there were sex differences in the administration of cardiovascular (CV) drugs in patients admitted to the intensive care unit of the Internal Medicine Clinic of Foča University Hospital (ICFUH). The study comprised 332 patients hospitalized at the ICFUH from January 1st to June 30th, 2019. The following data on leading CVD and risks related to CV drug administration were collected: age, hyperlipidemia (HLD), diabetes mellitus (DM), chronic kidney disease (CKD), liver disease (LD), heart failure (HF), hypertension (HTN), myocardial infarction (MI), and stroke (S). The amount of the CV drugs of interest (statins, antiplatelet drugs, calcium channel blockers, ACE inhibitors, beta blockers, diuretics) administered during hospitalization was expressed as the Defined Daily Dose (DDD)/100 bed-days (BD) for patients of both sexes separately. During hospitalization in the intensive care unit of ICFUH, female patients were less likely to be treated with statins than male patients (30.1 vs. 57.5 DDD/100 BD, P<0.05). There was no difference between sexes regarding the use of antihypertensive drugs. Women were less likely to be treated by antiplatelet therapy, more precisely by acetylsalicylic acid (30.4 vs. 36.9 DDD/100 BD, P<0.05). Our study indicates that there were sex differences in CV drug administration in ICFUH. Presuming that drugs used during hospitalization were at least partially a continuation of the previous therapy prescribed by the family doctor, it is possible that such differences exist in primary care.

Genome-Wide Characterization of a Highly Penetrant Form of Hyperlipoprotein(a)emia Associated With Genetically Elevated Cardiovascular Risk.

Background:Lp(a) (lipoprotein [a]) is a highly atherogenic lipoprotein strongly associated with coronary artery disease (CAD). Lp(a) concentrations are chiefly determined genetically. Investigation of large pedigrees with extreme Lp(a) using modern whole-genome approaches may unravel the genetic determinants underpinning this pathological phenotype.Methods:A large family characterized by high Lp(a) and increased CAD incidence was recruited by cascade screening. Plasma lipids, lipoproteins, and apolipoproteins concentrations, as well as the size of apo(a) isoforms, were determined enzymatically by high-resolution mass spectrometry and Western blot, respectively. Whole-exome sequencing was performed to search for rare defects in modifier genes. Genetic risk scores (GRS) for Lp(a) and CAD were calculated and their discriminative power was assessed.Results:Seventeen individuals displayed extreme Lp(a) levels including 6 with CAD. Whole-exome sequencing showed no hint for genetic defects outside the LPA locus. The extreme Lp(a) phenotype segregated with the presence of a short apo(a) isoform containing 21 Kringle IV domains. This allele was characterized by the presence of three rare strongly Lp(a) increasing single nucleotide polymorphisms and a significantly increased load of oxidized phospholipids per Lp(a) particle. An Lp(a) GRS consisting of 48 single nucleotide polymorphisms that represent 2001 genome-wide significant LPA single nucleotide polymorphisms, efficiently captured the hyper-Lp(a) phenotype and discriminated affected and nonaffected individuals with great accuracy. The genome-wide GRS for CAD, encompassing 6.6 million single nucleotide polymorphisms, was very high for most family members (>97.5 percentile of the reference population), but this observation was no longer valid when the contribution of the LPA locus was omitted.Conclusions:High-Lp(a) phenotypes can be successfully captured using the Lp(a) GRS even among closely related family members. In hyper-Lp(a) individuals, LPA can be a major locus driving a very high CAD GRS. This underpins the large contribution of the LPA locus to the cardiovascular genetic risk in families.

Causative Variants for Inherited Cardiac Conditions in a Southeast Asian Population Cohort.

Variable penetrance and late-onset phenotypes are key challenges for classifying causal as well as incidental findings in inherited cardiac conditions. Allele frequencies of variants in ancestry-specific populations, along with clinical variant analysis and interpretation, are critical to determine their true significance. Here, we carefully reviewed and classified variants in genes associated with inherited cardiac conditions based on a population whole-genome sequencing cohort of 4810 Singaporeans representing Southeast Asian ancestries. Eighty-nine (1.85%) individuals carried either pathogenic or likely pathogenic variants across 25 genes. Forty-six (51.7%) had variants in causal genes for familial hyperlipidemia, but there were also recurrent variants in SCN5A and MYBPC3, causal genes for inherited arrhythmia and cardiomyopathy, which, despite previous reports, we determined to lack criteria for pathogenicity. Our findings highlight the incidence of disease-related variants in inherited cardiac conditions and emphasize the value of large-scale sequencing in specific ancestries. Follow-up detailed phenotyping and analysis of pedigrees are crucial because assigning pathogenicity will significantly affect clinical management for individuals and their family members.

Abstract WP233: Socioeconomic Status And Comorbidity Variance In Ischemic Stroke

Introduction: Socioeconomic status (SES) is an upstream determinant of cerebrovascular disease comorbidities and subsequently ischemic stroke. Here we examined the association of SES and modifiable ischemic stroke risk factors. Methods: Hospitalized ischemic stroke patient data from 10/1/2015 - 12/31/2018 was obtained via the Healthcare Cost and Utilization Project Nationwide Inpatient Sample (NIS). Demographic characteristics of age, sex, race, US region, SES (defined as median household income range by zip code) and ischemic stroke risk factors of atrial fibrillation/flutter (AF), type II diabetes (DM), hypertension (HTN), hyperlipidemia (HLD), tobacco use, and obesity were identified using published ICD-10 codes. Multivariable logistic regression was used to assess each condition individually and identify which comorbidities were associated with specific socioeconomic quartiles (Q1, Q4) when adjusted for the abovementioned demographics. Results: Of the 382,734 adult ischemic stroke patients identified, mean age was 70 ±14.2 years and 50.3% were female. Socioeconomic status quartiles ranged from &lt;$43,749 (Q1) to &gt;$73,000 (Q4); 30.9% of ischemic stroke patients were in SES Q1 (vs 19.1% in SES Q4). Patients in Q1 experienced ischemic stroke at a younger age (67.9 ±14.1) as compared to patients in Q4 (72.4 ±14), p&lt;0.001. In adjusted models with Q4 as reference, Q1 patients had increased odds for DM [OR 1.27, p&lt;0.001, 95% CI 1.24 - 1.29], obesity [OR 1.05, p&lt;0.004, CI 1.02 - 1.08], and tobacco use [OR 1.66, p&lt;0.001, CI 1.51 - 1.83]. Conversely, Q1 patients had decreased odds of AF [OR 0.91, p&lt;0.001, CI 0.89 - 0.93] and HLD [OR 0.81, p&lt;0.001, CI 0.79 - 0.82]. There was no significant association between SES quartile and HTN. Conclusion: Lower SES was associated with higher odds of specific ischemic stroke risk factors. While the etiology of the risk factor variance is beyond the scope of current data analysis, the cause is likely multifactorial and influenced by underlying detection bias, income inequity, and level of education/health literacy. Further research and subgroup analysis is warranted as it may impact future preventative measures and treatment protocols.

Assessment of causal direction between thyroid function and cardiometabolic health: a Mendelian randomization study.

BACKGROUNDGrowing evidence have demonstrated that thyroid hormones have been involved in the processes of cardiovascular metabolism. However, the causal relationship of thyroid function and cardiometabolic health remains partly unknown.METHODSThe Mendelian randomization (MR) was used to test genetic, potentially causal relationships between instrumental variables and cardiometabolic traits. Genetic variants of free thyroxine (FT4) and thyrotropin (TSH) levels within the reference range were used as instrumental variables. Data for genetic associations with cardiometabolic diseases were acquired from the genome-wide association studies of the FinnGen, CARDIoGRAM and CARDIoGRAMplusC4D, CHARGE, and MEGASTROKE. This study was conducted using summary statistic data from large, previously described cohorts. Association between thyroid function and essential hypertension (EHTN), secondary hypertension (SHTN), hyperlipidemia (HPL), type 2 diabetes mellitus (T2DM), ischemic heart disease (IHD), myocardial infarction (MI), heart failure (HF), pulmonary heart disease (PHD), stroke, and non-rheumatic valve disease (NRVD) were examined.RESULTSGenetically predicted FT4 levels were associated with SHTN (odds ratio = 0.48; 95% CI = 0.04−0.82,P = 0.027), HPL (odds ratio = 0.67; 95% CI = 0.18−0.88,P = 0.023), T2DM (odds ratio = 0.80; 95% CI = 0.42−0.86,P = 0.005), IHD (odds ratio = 0.85; 95% CI = 0.49−0.98,P = 0.039), NRVD (odds ratio = 0.75; 95% CI = 0.27−0.97,P = 0.039). Additionally, genetically predicted TSH levels were associated with HF (odds ratio = 0.82; 95% CI = 0.68−0.99,P = 0.042), PHD (odds ratio = 0.75; 95% CI = 0.32−0.82,P = 0.006), stroke (odds ratio = 0.95; 95% CI = 0.81−0.97,P = 0.007). However, genetically predicted thyroid function traits were not associated with EHTN and MI. CONCLUSIONSOur study suggests FT4 and TSH are associated with cardiometabolic diseases, underscoring the importance of the pituitary-thyroid-cardiac axis in cardiometabolic health susceptibility.

Comorbidity analysis in obstructive sleep apnea patients

Background/Aim: Obstructive sleep apnea (OSA) is a syndrome that causes complete or partial cessation of breathing and as a result of several pathways, hypertension (HT), type 2 diabetes mellitus (DM), and hyperlipidemia (HL) are usually seen as comorbidities. The main problem in the literature is, due to the presence of some confounders, especially body mass index (BMI), it is still not clear that if OSA is an independent risk factor for these comorbidities. This issue may be shown more clearly with BMI and age-matched subjects since they are strongly related to metabolic diseases and HT. Comparison of the ratios of the presence of DM, HL, and hypertension between the age and BMI matched groups is primarily aimed in the present study to see if moderate and severe OSA could be an independent risk factor for these comorbidities. Methods: Patients admitted with sleep problems were retrospectively scanned from the patient files and cases with polysomnography and routine blood test were included. The body mass indexes, ages, smoking, and alcohol habits of the cases were noted. Two groups were formed based on polysomnography, taking a threshold value of the apnea-hypopnea index (AHI) of 15. Group 1 had cases with AHI &lt;15 (normal and mild apnea patients) and Group 2 had cases with AHI≥15 (moderate/severe apnea patients). Subjects were accepted as having DM, HL, or HT if they are on medication or if their examination and/or laboratory results show the presence of these diseases. The ratios of these diseases within the groups were compared. Statistical Analysis: Numerical variables were given as mean±standard deviation. Categorical variables were shown as a number. Categorical variables were tested with the Chi-Square test or Fisher’s exact test and an independent T-test was used for two independent groups. Statistical significance was accepted as p&lt;0.05. Results: There were 22 cases with an AHI&lt;15 and 17 cases with an AHI ≥15, with similar mean BMI and age (p= 0.206, p= 0.054 respectively). The ratio of hypertension was found significantly higher in moderate/severe OSA patients (47% vs 5%; p=0.005). On the other hand, the ratios of DM and HL were found statistically similar (p=0.49, p=1.0 respectively). Conclusion: This study aimed to show the possible independent role of sleep apnea in metabolic diseases and HT, by creating two groups with similar BMI, age, and cigarette and alcohol habits. The results support moderate/Severe OSA as an independent risk factor for hypertension, while DM and HL are thought to be in close relationship with BMI.

Role of hyperuricemia in patients with essential hypertension: A hospital-based case–control study

Background: Essential hypertension (EHT) poses as a major health issue in developed countries. It shows a strong association with cardiovascular disease and significantly contributes to patient morbidity and mortality, as well as economic burden. The association of hyperuricemia with EHT is demonstrated by several researchers. It is postulated that increased serum uric acid (SUA) level is thought to play a pathogenic role in the evolution of EHT. Aim and Objective: The aim of this study was to establish the relationship between SUA and EHT and also to determine the correlation coefficient between SUA levels and blood pressure (BP) in subjects with EHT. Materials and Methods: This hospital-based case–control study included 50 newly diagnosed and untreated hypertensive patients of all genders in age group of 35–65 years having BP ≥140/90 mm Hg as cases. Fifty age- and sex-matched and normotensive subjects were included as controls. Patients with history of diabetes mellitus, renal diseases, chronic liver disease, familial hyperlipidemia, gout, smoking, alcohol consumption, obesity, and patients on lipid lowering drugs were excluded from the study. SUA was measured in all study and control subjects by standard method. Results: Mean SUA level was significantly higher in EHT group (7.83 ± 0.16) as compared to control group (4.99 ± 0.31) (P &lt; 0.001). Positive and significant correlation was found between SUA and systolic BP (R2 = 0.59, P &lt; 0.001), diastolic BP (DBP) (R2 = 0.59, P &lt; 0.001), and mean BP (R2 = 0.62, P &lt; 0.001). Hyperuricemia was observed in significantly higher proportion in cases (n = 47, 94%) as compared to controls (n = 6, 12%) (P &lt; 0.001). Conclusions: Increased SUA level has significant association with EHT after regulating several confounding factors. The count of hyperuricemic individuals as well as mean SUA level was significantly higher in newly diagnosed cases of hypertension in comparison to normotensive controls. There was significant positive association between SUA and BP in hypertensive cases.

The First Report of a Real-World Experience with PCSK9-Inhibitor in a Large Familial Hyperlipidemia and Very-High Risk Middle Eastern Population

The First Report of a Real-World Experience with PCSK9-Inhibitor in a Large Familial Hyperlipidemia and Very-High Risk Middle Eastern Population

Effect of Emodin on Hyperlipidemia and Hepatic Lipid Metabolism in Zebrafish Larvae Fed a High-Cholesterol Diet.

Hyperlipidemia (HLP) is a complex pathological condition results from lipid metabolism disorder, which is closely related to obesity, atherosclerosis and steatohepatitis. Emodin (EM), a natural anthraquinone, exhibits prominent hypolipidemic effects. However, its exact mechanism is still unclear. In this study, we successfully established hyperlipidemic zebrafish model induced by 4 % high-cholesterol diet (HCD) for 10 days and explored the anti-hyperlipidemic roles and underlying mechanisms of EM. The results indicated that EM attenuated the mortality and body mass index (BMI) of zebrafish with HLP, and ameliorated abnormal lipid levels involved in TC, TG, LDL-C and HDL-C levels. Besides, EM effectively reduced lipid accumulation in blood vessels and liver, alleviated hepatic histological damage, and inhibited vascular neutrophil inflammation. Finally, the mRNA expression of molecules related to lipid metabolism were studied by using real-time quantitative polymerase chain reaction (RT-qPCR) to investigated the underlying mechanism. Further results found that treatment with EM up-regulated AMPKα, LDLR, ABCA1 and ABCG1, and down-regulated SREBP-2, PCSK9 and HMGCR expression. In conclusion, EM showed a prominent mitigative effect on lipid metabolism disorder in zebrafish larvae with HCD-stimulated HLP, which was associated with the enhancement of LDL-C uptake and reverse cholesterol transport, and inhibition of cholesterol synthesis.

Unraveling the molecular mechanisms of hyperlipidemia using integrated lncRNA and mRNA microarray data.

Long non-coding RNAs (lncRNAs) have key roles in various diseases; however, their functions in hyperlipidemia (HLP) have remained elusive. In the present study, microarray technology was utilized to analyze the differential expression of lncRNAs and mRNAs in liver tissues of apolipoprotein E-/- mice as a model of HLP compared with control mice. A total of 104 and 96 differentially expressed lncRNAs and mRNAs, respectively, were identified. Differentially expressed genes were significantly enriched in biological processes such as nitric oxide biosynthesis, innate immune response and inflammatory response. Finally, two pairs of target genes and 38 transcription factors with regulatory functions in HLP were predicted based on the lncRNA and mRNA co-expression network. The lncRNA expression profile was significantly altered in liver tissues of the mouse model of HLP and may provide novel targets for research into treatments.

Clusters of the Risk Markers and the Pattern of Premature Coronary Heart Disease: An Application of the Latent Class Analysis

Background: Coronary heart disease (CHD) is the major cause of mortality in the world with a significant impact on the younger population. The aim of this study was to identify prematurity among patients with coronary artery bypass graft surgery (CABG) based on the clustering of CHD risk factors.Methods: Patients were recruited from an existing cohort of candidates for CABG surgery named Tehran Heart Center Coronary Outcome Measurement (THC-COM). A latent class analysis (LCA) model was formed using 11 potential risk factors as binary variables: cigarette smoking, obesity, diabetes, family history of CHD, alcohol use, opium addiction, hypertension, history of stroke, history of myocardial infarction (MI), peripheral vascular disease (PVD), and hyperlipidemia (HLP). We analyzed our data to figure out how the patients are going to be clustered based on their risk factors.Results: For 566 patients who were studied, the mean age (SD) and BMI of patients were 59.1 (8.9) and 27.3 (4.1), respectively. The LCA model fit with two latent classes was statistically significant (G2 = 824.87, df = 21, p < 0.0001). The mean (SD) age of patients for Class I and Class II was 55.66 (8.55) and 60.87 (8.66), respectively. Class I (premature) was characterized by a high probability of smoking, alcohol consumption, opium addiction, and a history of MI (P < 0.05), and class II by a high probability of obesity, diabetes, and hypertension.Conclusion: Latent class analysis calculated two groups of severe CHD with distinct risk markers. The younger group, which is characterized by smoking, addiction, and the history of MI, can be regarded as representative of premature CHD.