MicroRNA-145 Regulates the Differentiation of Adipose Stem Cells Toward Microvascular Endothelial Cells and Promotes Angiogenesis.

Rationale: Adipose-derived stem cells (ASCs) are a potential adult mesenchymal stem cell source for restoring endothelial function in ischemic tissues. However, the mechanism that promotes ASCs differentiation toward endothelial cells (ECs) is not known.

Objective: To investigate the mechanisms of ASCs differentiation into ECs.

Macrophages of genetically characterized familial hypercholesterolaemia patients show up-regulation of LDL-receptor-related proteins.

Familial hypercholesterolaemia (FH) is a major risk for premature coronary heart disease due to severe long-life exposure to high LDL levels. Accumulation of LDL in the vascular wall triggers atherosclerosis with activation of the innate immunity system. Here, we have investigated (i) gene expression of LDLR and LRPs in peripheral blood cells (PBLs) and in differentiated macrophages of young FH-patients; and (ii) whether macrophage from FH patients have a differential response when exposed to high levels of atherogenic LDL.

PAR2-SMAD3 in microvascular endothelial cells is indispensable for vascular stability via tissue factor signaling.

Tissue factor (TF) signaling regulates gene expression and protein synthesis leading to the modulation of cell function. Recently, we have demonstrated in microvascular endothelial cells (mECs) that TF signaling induces activation of ETS1 transcription factor. Because combinatorial control is a characteristic property of ETS family members, involving the interaction between ETS1 and other transcription factors, here we investigate whether additional transcription factors are involved in TF-induced angiogenesis.

rs11613352 polymorphism (TT genotype) associates with a decrease of triglycerides and an increase of HDL in familial hypercholesterolemia patients.

Introduction And Objectives: Recent genome-wide association studies have identified a locus on chromosome 12q13.3 associated with plasma levels of triglyceride and high-density lipoprotein cholesterol, with rs11613352 being the lead single nucleotide polymorphism in this genome-wide association study locus. The aim of the study is to investigate the involvement of rs11613352 in a population with high cardiovascular risk due to familial hypercholesterolemia.

Monocyte-secreted Wnt5a interacts with FZD5 in microvascular endothelial cells and induces angiogenesis through tissue factor signaling.

Angiogenesis during reactive and pathologic processes is characteristically associated with inflammation. Inflammatory cells participate in angiogenesis by secreting different molecules that affect endothelial cell functions. We had previously shown that induced tissue factor (TF) expression in activated microvascular endothelial cells (mEC) is able to induce angiogenesis via autocrine regulation.

Ets-1 transcription is required in tissue factor driven microvessel formation and stabilization.

Tissue factor (TF) has well-recognized roles as initiator of blood coagulation as well as an intracellular signaling receptor. TF signaling regulates gene transcription and protein translation. Recently, we have shown that TF-induced mature neovessel formation is ultimately driven by CCL2 expression.

LRP1 gene polymorphisms are associated with premature risk of cardiovascular disease in patients with familial hypercholesterolemia.

Introduction And Objectives: LRP1 gene overexpression in atherosclerotic plaque is associated with increased lipid uptake through the vascular wall. The aim of the study was to analyze whether LRP1 modulates the genetic risk of developing premature cardiovascular disease in familial hypercholesterolemia, using single nucleotide polymorphism association analysis.

Methods: Ten polymorphisms of the LRP1 gene (rs715948, rs1799986, rs1800127, rs7968719, rs1800176, rs1800194, rs1800181, rs1140648, rs1800164, and rs35282763) were genotyped in 339 patients (77 with premature cardiovascular disease and 262 without) in the SAFEHEART study.

Low-density lipoprotein receptor-related protein 1 mediates hypoxia-induced very low density lipoprotein-cholesteryl ester uptake and accumulation in cardiomyocytes.

Aims: The myocardium accumulates intracellular lipids under ischaemic conditions, and myocardial fat deposition is closely associated with cardiac dysfunction. Our aims were to analyse the effect of hypoxia on low-density lipoprotein receptor-related protein 1 (LRP1) expression in neonatal rat ventricular myocytes (NRVM) and cardiac-derived HL-1 cells and the molecular mechanisms involved in this effect, to determine the role of LRP1 in the very low density lipoprotein (VLDL) uptake by hypoxic cardiomyocytes, and to study the effect of hypoxia on lipoprotein receptor expression and myocardial lipid profile in an in vivo porcine experimental model of acute myocardial infarction.

Methods And Results: Thin-layer chromatography after lipid extraction showed that VLDL exposure leads to cholesteryl ester (CE) and triglyceride (TG) accumulation in a dose-dependent manner and that hypoxic conditions further increased VLDL-derived intracellular lipid accumulation in HL-1 cells.

Tissue factor regulates microvessel formation and stabilization by induction of chemokine (C-C motif) ligand 2 expression.

Objective: Tissue factor (TF) triggers arterial thrombosis. TF is also able to initiate cellular signaling mechanisms leading to angiogenesis. Because high cardiovascular risk atherosclerotic plaques show significant angiogenesis, our objective was to investigate whether TF is able to trigger and stabilize atherosclerotic plaque neovessel formation.

Hypoxia stimulates low-density lipoprotein receptor-related protein-1 expression through hypoxia-inducible factor-1α in human vascular smooth muscle cells.

Objective: Hypoxia is considered a key factor in the progression of atherosclerotic lesions. Low-density lipoprotein receptor-related protein (LRP1) plays a pivotal role in the vasculature. The aim of this study was to investigate the effect of hypoxia on LRP1 expression and function in vascular smooth muscle cells (VSMC) and the role of hypoxia-inducible factor-α (HIF-1α).

Fibulin-5 is up-regulated by hypoxia in endothelial cells through a hypoxia-inducible factor-1 (HIF-1α)-dependent mechanism.

Hypoxia modulates gene expression and affects multiple aspects of endothelial cell biology. Fibulin-5 (FBLN5) is an extracellular matrix protein essential for elastic fiber assembly and vasculogenesis that participates in vascular remodeling and controls endothelial cell adhesion, motility, and proliferation. In this context, we aimed to analyze FBLN5 regulation by hypoxia in endothelial cells.

Structural (betaalpha)8 TIM barrel model of 3-hydroxy-3-methylglutaryl-coenzyme A lyase.

This study describes three novel homozygous missense mutations (S75R, S201Y, and D204N) in the 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) lyase gene, which caused 3-hydroxy-3-methylglutaric aciduria in patients from Germany, England, and Argentina. Expression studies in Escherichia coli show that S75R and S201Y substitutions completely abolished the HMG-CoA lyase activity, whereas D204N reduced catalytic efficiency to 6.6% of the wild type.

CDP-choline prevents glutamate-mediated cell death in cerebellar granule neurons.

Cytidine 5'-diphosphocholine (CDP-choline) has been shown to reduce neuronal degeneration induced in central nervous system (CNS) injury. However, the precise mechanism underlying the neuroprotective properties of this molecule is still unknown. Excitotoxicity causes cell death in CNS injury (trauma or ischemia) and has also been involved in neurodegenerative diseases.

The diagnosis of mitochondrial HMG-CoA synthase deficiency.

Deficiency of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) synthase, the only disorder exclusively affecting hepatic ketogenesis, is a cause of hypoglycemic coma. We report that the diagnosis can be made by typical laboratory findings (hypoketosis, elevated free fatty acids, normal acylcarnitines, specific urinary organic acids) during acute episodes.