Ultra-small phospholipid nanoparticles in the treatment of combined hyperlipidemia: a randomized placebo-controlled clinical trial.

Background And Purpose: Combined hyperlipidemia is associated with an increased risk of cardiovascular events. This clinical trial investigated phospholipovit (essential phospholipids, Institute of Biomedical Chemistry, Moscow, Russia), an ultra-small phospholipid nanoparticle (micelles), targeted to phospholipids of HDL in lowering non-HDL-cholesterol (non-HDL-C) and triglycerides (TG) levels in patients with combined hyperlipidemia and moderate cardiovascular risk.

Experimental Approach: A randomized, double-blinded, placebo-controlled phase II trial was conducted on 100 patients.

iPSC-Derived Endothelial Cells Reveal LDLR Dysfunction and Dysregulated Gene Expression Profiles in Familial Hypercholesterolemia.

Defects in the low-density lipoprotein receptor (LDLR) are associated with familial hypercholesterolemia (FH), manifested by atherosclerosis and cardiovascular disease. LDLR deficiency in hepatocytes leads to elevated blood cholesterol levels, which damage vascular cells, especially endothelial cells, through oxidative stress and inflammation. However, the distinctions between endothelial cells from individuals with normal and defective LDLR are not yet fully understood.

Calling and Phasing of Single-Nucleotide and Structural Variants of the Gene Using Oxford Nanopore MinION.

The locus has clinical significance for lipid metabolism, Mendelian familial hypercholesterolemia (FH), and common lipid metabolism-related diseases (coronary artery disease and Alzheimer's disease), but its intronic and structural variants are underinvestigated. The aim of this study was to design and validate a method for nearly complete sequencing of the gene using long-read Oxford Nanopore sequencing technology (ONT). Five PCR amplicons from of three patients with compound heterozygous FH were analyzed.

Induced pluripotent stem cell line ICGi037-A, obtained by reprogramming peripheral blood mononuclear cells from a patient with familial hypercholesterolemia due to heterozygous p.Trp443Arg mutations in LDLR.

Familial hypercholesterolemia (FH) is an autosomal dominant disorder increasing premature cardiovascular diseases risk due to atherosclerosis. Pathogenic mutations in the LDLR gene cause most FH cases. Available treatments are effective not for all LDLR mutations.

Induced pluripotent stem cell line ICGi038-A, obtained by reprogramming peripheral blood mononuclear cells from a patient with familial hypercholesterolemia due to compound heterozygous c.1246C > T/c.940 + 3_940 + 6del mutations in LDLR.

The development of cellular models for familial hypercholesterolemia (FH) is an important direction for creating new approaches to atherosclerosis treatment. Pathogenic mutations in the LDLR gene are the main FH source. We generated an iPSC line from peripheral blood mononuclear cells of the patient with compound heterozygous c.

Induced pluripotent stem cell line ICGi036-A generated by reprogramming peripheral blood mononuclear cells from a patient with familial hypercholesterolemia caused due to compound heterozygous p.Ser177Leu/p.Cys352Arg mutations in LDLR.

Familial hypercholesterolemia (FH) is a monogenic disease, leading to atherosclerosis due to a high level of low-density lipoprotein cholesterol. Most cases of the disease are based on pathological variants in the LDLR gene. Hepatocyte-like and endothelial cells derived from individual iPSCs are a good model for developing new approaches to therapy.

Lipoprotein(a) level and apolipoprotein(a) phenotype as predictors of long-term cardiovascular outcomes after coronary artery bypass grafting.

Objective: To evaluate the relationships of lipoprotein(a) (Lp(a)) concentration and apolipoprotein(a) (apo(a)) phenotype to major adverse cardiovascular events after coronary artery bypass grafting (CABG) in long-term follow-up.

Methods: This single-center study included 356 patients with stable coronary heart disease (CHD) who underwent successful CABG. At baseline, we assessed the patient's risk factor profile for atherosclerosis, Lp(a) concentration and apo(a) phenotype.

Effect of intensive versus standard lipid-lowering treatment with atorvastatin on the progression of calcified coronary atherosclerosis over 12 months: a multicenter, randomized, double-blind trial.

Background: Recent clinical trials have suggested that intensive versus standard lipid-lowering therapy provides for additional benefit. Electron-beam computed tomography provides the opportunity to quantify the progression of coronary artery calcification (CAC) in serial measurements.

Methods And Results: In a multicenter, randomized, double-blind trial, 471 patients (age 61+/-8 years) who had no history of coronary artery disease and no evidence of high-grade coronary stenoses (>50% diameter reduction) were randomized if they had > or =2 cardiovascular risk factors and moderate calcified coronary atherosclerosis as evidenced by a CAC score > or =30.

Antioxidants decreases the intensification of low density lipoprotein in vivo peroxidation during therapy with statins.

The oxidative modification of low density lipoprotein (LDL) is thought to play an important role in atherogenesis. Drugs of beta-hydroxy-beta-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) family are usually used as a very effective lipid-lowering preparations but they simultaneously block biosynthesis of both cholesterol and ubiquinone Q10 (coenzyme Q), which is an intermediate electron carrier in the mitochondrial respiratory chain. It is known that reduced form of ubiquinone Q10 acts in the human LDL as very effective natural antioxidant.

Sialyltransferase activity of human plasma and aortic intima is enhanced in atherosclerosis.

Sialyltransferase activity has been determined in membrane preparations containing the Golgi apparatus that were isolated from atherosclerotic and normal human aortic intima as well as in plasma of patients with documented atherosclerosis and healthy donors by measuring the transfer of N-acetylneuraminic acid (NeuAc) from CMP-NeuAc to asialofetuin. The asialofetuin sialyltransferase activity was found to be 2 times higher in the atherosclerotic intima as compared to the normal intima and 2-fold higher in patients' plasma than in that from healthy donors. The mean values of the apparent Michaelis constant (K(m)) for the sialylating enzyme for both tissues did not differ and were close for the intima and plasma.