Mendelian randomization studies of lifestyle-related risk factors for stroke: a systematic review and meta-analysis.

Objective: Stroke risk factors often exert long-term effects, and Mendelian randomization (MR) offers significant advantages over traditional observational studies in evaluating the causal impact of these factors on stroke. This study aims to consolidate and evaluate the relationships between potential causal factors and stroke risk, drawing upon existing MR research.

Methods: A comprehensive search for MR studies related to stroke was conducted up to August 2023 using databases such as PubMed, Web of Science, Embase, and Scopus.

PCSK9 in metabolism and diseases.

PCSK9 is a serine protease that regulates plasma levels of low-density lipoprotein (LDL) and cholesterol by mediating the endolysosomal degradation of LDL receptor (LDLR) in the liver. When PCSK9 functions unchecked, it leads to increased degradation of LDLR, resulting in elevated circulatory levels of LDL and cholesterol. This dysregulation contributes to lipid and cholesterol metabolism abnormalities, foam cell formation, and the development of various diseases, including cardiovascular disease (CVD), viral infections, cancer, and sepsis.

Assessing the Impact of Serum Calcium, 25-Hydroxy Vitamin D, Ferritin, and Uric Acid Levels on Colorectal Cancer Risk.

Background: The aim of this study is to investigate whether vitamin D, calcium, ferritin, and uric acids play a beneficial biomarker role in the prevention of colorectal cancer (CRC) risk.

Methods: The case-control design was employed, including 650 CRC cases and 650 controls aged 35 to 70 years, comprising both men and women. The study encompasses sociodemographic data, clinical information, radiological diagnoses, and biochemical measurements.

Proteome-wide association studies for blood lipids and comparison with transcriptome-wide association studies.

Blood lipid traits are treatable and heritable risk factors for heart disease, a leading cause of mortality worldwide. Although genome-wide association studies (GWASs) have discovered hundreds of variants associated with lipids in humans, most of the causal mechanisms of lipids remain unknown. To better understand the biological processes underlying lipid metabolism, we investigated the associations of plasma protein levels with total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL) cholesterol, and low-density lipoprotein (LDL) cholesterol in blood.

Determination of selected oxysterol levels, oxidative stress, and macrophage activation indicators in children and adolescents with familial hypercholesterolemia.

Aim: Elevated levels of cholesterol in the bloodstream, also referred to as hypercholesterolemia, pose a significant risk for the onset of cardiovascular and cerebrovascular diseases. Oxysterols, cholesterol-derived oxidized compounds that form enzymatically or non-enzymatically, contribute to the development of atherosclerosis and coronary artery disease. This study aimed to examine the critical oxysterol levels in children and adolescents with hypercholesterolemia and explore the correlation between these levels, oxidative stress, and atherosclerosis progression.

Identification of a homozygous variant in ABCG5 by panel sequencing in a Pakistani family with sitosterolemia: Genotype-phenotype correlation and management considerations.

Sitosterolemia is a rare autosomal recessive disorder characterized by impaired excretion of plant sterols, leading to their accumulation in tissues and organs. We identified a hitherto unreported homozygous variant, in ATP-binding cassette sub-family G member 5 (ABCG5) (NM_022436.3) c.

Performance of LDL-C only compared to the Dutch Lipid Clinic Network Score for screening of familial hypercholesterolaemia: the Austrian experience and literature review.

Aims: Familial hypercholesterolaemia (FH) is a severely underdiagnosed, inherited disease, causing dyslipidaemia and premature atherosclerotic cardiovascular disease. In order to facilitate screening in a broad clinical spectrum, we aimed to analyse the current yield of routine genetic diagnostics for FH and to evaluate the performance of the Dutch Lipid Clinic Network Score (DLCNS) compared to a single value, the off-treatment LDL-cholesterol exceeding 190 mg/dL.

Methods And Results: We investigated all patients that underwent molecular genotyping routinely performed for FH over a 4-year period in two Austrian specialist lipid clinics.

Decreased lipidated ApoE-receptor interactions confer protection against pathogenicity of ApoE and its lipid cargoes in lysosomes.

While apolipoprotein E (APOE) is the strongest genetic modifier for late-onset Alzheimer's disease (LOAD), the molecular mechanisms underlying isoform-dependent risk and the relevance of ApoE-associated lipids remain elusive. Here, we report that impaired low-density lipoprotein (LDL) receptor (LDLR) binding of lipidated ApoE2 (lipApoE2) avoids LDLR recycling defects observed with lipApoE3/E4 and decreases the uptake of cholesteryl esters (CEs), which are lipids linked to neurodegeneration. In human neurons, the addition of ApoE carrying polyunsaturated fatty acids (PUFAs)-CE revealed an allelic series (ApoE4 > ApoE3 > ApoE2) associated with lipofuscinosis, an age-related lysosomal pathology resulting from lipid peroxidation.

Variants in LPA are associated with Familial Hypercholesterolaemia: whole genome sequencing analysis in the 100,000 Genomes Project.

Background: Familial Hypercholesterolaemia (FH) is an inherited disease of high LDL-cholesterol (LDL-C) caused by defects in LDLR, APOB, APOE and PCSK9 genes. A pathogenic variant cannot be found in ∼60% of clinical FH patients. Using whole genome sequencing (WGS) we examined genetic determinants of FH.

Evolocumab treatment reduces carotid intima-media thickness in paediatric patients with heterozygous familial hypercholesterolaemia.

Aim: Children with heterozygous familial hypercholesterolaemia (HeFH) show greater carotid intima-media thickness (cIMT). Evolocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor monoclonal antibody, substantially reduced low-density lipoprotein cholesterol (LDL-C) and modestly reduced lipoprotein(a) in children with HeFH. We investigated evolocumab's effect on cIMT progression.

Sphingosine 1-phosphate receptor 1signaling in macrophages reduces atherosclerosis in LDL receptor-deficient mice.

Sphingosine 1-phosphate (S1P) is a lysosphingolipid with antiatherogenic properties, but mechanisms underlying its effects remain unclear. We here investigated atherosclerosis development in cholesterol-rich diet-fed LDL receptor-deficient mice with high or low overexpression levels of S1P receptor 1 (S1P1) in macrophages. S1P1-overexpressing macrophages showed increased activity of transcription factors PU.

Development of a hamster model of spontaneous hypertriglyceridemia in diabetes.

Hypertriglyceridemia (HTG) often accompanies diabetes and is considered a risk factor for diabetic vascular complications. However, inducing diabetic HTG typically requires high-fat diets in certain animal models. Leveraging our newly developed LDL receptor knockout hamster model, which exhibits features akin to human lipid metabolism, we sought to determine whether these animals would develop HTG without dietary manipulations in diabetes.

Leukemia inhibitory factor receptor inhibition by EC359 reduces atherosclerotic stenosis grade in Ldlr mice.

Cytokines are involved in all stages of atherosclerosis, generally contributing to disease progression. Previously, members of the Interleukin (IL)-6 cytokine family, such as IL-6, oncostatin M, and cardiotrophin-1, have been extensively studied in atherosclerosis. However, the role of leukemia inhibitory factor (LIF), member of the IL-6 family, and its receptor (LIFR), remains to be further elucidated.

CYP3A4*1B and CYP3A5*3 SNPs significantly impact the response of Egyptian candidates to high-intensity statin therapy to atorvastatin.

Background: A single nucleotide polymorphism (SNP) is a variation in the DNA sequence that results from the alteration of a single nucleotide in the genome. Atorvastatin is used to treat hypercholesterolemia. It belongs to a class of drugs called statins, which lower elevated levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C).

Antarctic Krill Oil Supplementation Attenuates Hypercholesterolemia, Fatty Liver, and Oxidative Stress in Diet-Induced Obese Mice.

Background: Several Previous studies indicate that consuming krill oil may aid in reducing hypercholesterolemia and improving cholesterol metabolism. Therefore, our study was designed to investigate the effectiveness of Antarctic krill oil () (ESKO) in combating obesity and lowering fat/lipid/cholesterol levels.

Methods: The study aimed to investigate the molecular docking model targeting 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) using ESKO-derived eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and astaxanthin.

Phenotype in Individuals with Heterozygous Rare Variants in Encoding Hepatic Lipase.

Hepatic lipase deficiency is a rare genetic condition caused by biallelic loss-of-function variants in the gene encoding hepatic lipase. These variants reduce or abolish the protein's lipolytic activity, resulting in elevated plasma lipids. The condition is classified as autosomal recessive, since dyslipidemia is inconsistently observed in heterozygous patients with only one variant.

Alkaline Mineral Complex Water Attenuates Transportation-Induced Hepatic Lipid Metabolism Dysregulation by AMPKα-SREBP-1c/PPARα Pathways.

Transportation, an unavoidable process in livestock farming, causes metabolic disorders in the body, which then lead to endocrine disruption, being immunocompromised, and growth suppression. Lipid metabolism dysregulation is a critical phenotype induced by transportation. The liver is a vital organ in lipid metabolism, with a role in both lipid synthesis and lipolysis.

Association analysis of gut microbiota with LDL-C metabolism and microbial pathogenicity in colorectal cancer patients.

Background: Colorectal cancer (CRC) is the most common gastrointestinal malignancy worldwide, with obesity-induced lipid metabolism disorders playing a crucial role in its progression. A complex connection exists between gut microbiota and the development of intestinal tumors through the microbiota metabolite pathway. Metabolic disorders frequently alter the gut microbiome, impairing immune and cellular functions and hastening cancer progression.

Homozygous familial hypercholesterolemia in Spain. Data from Registry of the Spanish Atherosclerosis Society.

Unlabelled: Homozygous familial hypercholesterolemia (HoFH) is a rare disease characterized by the presence of two pathogenic variants in the LDLR, APOB, PCSK9 or LDLRAP1 genes, which cause very high levels of LDL cholesterol and premature atherosclerotic cardiovascular disease (ASCVD).The objective of this study is to analyze the current situation regarding diagnosis, cardiovascular disease, lipid-lowering treatment and degree of control of lipids in patients with HoFH in the National Dyslipidemia Registry of the Spanish Atherosclerosis Society.

Methods: Subjects with HoFH, confirmed by the presence of two pathogenic variants in the genes mentioned above, included in the registry from 2013 to June 2023 with an updated review were analyzed.

Gastroesophageal reflux disease influences blood pressure components, lipid profile and cardiovascular diseases: Evidence from a Mendelian randomization study.

Background: Gastroesophageal reflux disease (GERD) is a prevalent gastrointestinal disorder associated with a range of cardiovascular and metabolic complications. However, the relationship between GERD and blood pressure components, lipid profile, and cardiovascular diseases remains unclear.

Methods: Leveraging genetic variants associated with GERD as instrumental variables, we performed this Mendelian randomization (MR) analyses.