Bernal-López, María RosaLlorente-Cortés, VicentaGómez-Carrillo, VíctorLópez-Carmona, DoloresCalleja, FernandoGómez-Huelgas, RicardoBadimón, LinaTinahones, Francisco J2013-02-082013-02-082012-07-24Bermal-López MR, Llorente Cortés V, Gómez Carrillo V, López Carmona D, Calleja F, Gómez Huelgas R, et al. Alterations of specific biomarkers of metabolic pathways in vascular tree from patients with Type 2 diabetes. Cardiovasc Diabetol; 11:86http://hdl.handle.net/10668/762Journal Article; Research Support, Non-U.S. Gov't;The aims of this study were to check whether different biomarkers of inflammatory, apoptotic, immunological or lipid pathways had altered their expression in the occluded popliteal artery (OPA) compared with the internal mammary artery (IMA) and femoral vein (FV) and to examine whether glycemic control influenced the expression of these genes. The study included 20 patients with advanced atherosclerosis and type 2 diabetes mellitus, 15 of whom had peripheral arterial occlusive disease (PAOD), from whom samples of OPA and FV were collected. PAOD patients were classified based on their HbA1c as well (HbA1c ≤ 6.5) or poorly (HbA1c > 6.5) controlled patients. Controls for arteries without atherosclerosis comprised 5 IMA from patients with ischemic cardiomyopathy (ICM). mRNA, protein expression and histological studies were analyzed in IMA, OPA and FV. After analyzing 46 genes, OPA showed higher expression levels than IMA or FV for genes involved in thrombosis (F3), apoptosis (MMP2, MMP9, TIMP1 and TIM3), lipid metabolism (LRP1 and NDUFA), immune response (TLR2) and monocytes adhesion (CD83). Remarkably, MMP-9 expression was lower in OPA from well-controlled patients. In FV from diabetic patients with HbA1c ≤6.5, gene expression levels of BCL2, CDKN1A, COX2, NDUFA and SREBP2 were higher than in FV from those with HbA1c >6.5. The atherosclerotic process in OPA from diabetic patients was associated with high expression levels of inflammatory, lipid metabolism and apoptotic biomarkers. The degree of glycemic control was associated with gene expression markers of apoptosis, lipid metabolism and antioxidants in FV. However, the effect of glycemic control on pro-atherosclerotic gene expression was very low in arteries with established atherosclerosis.enAterosclerosisMarcadores BiológicosIsquemia MiocárdicaInflamaciónDiabetes MellitusArteriopatías OclusivasInhibidor p21 de las Quinasas Dependientes de la CiclinaCiclooxigenasa 2Metaloproteinasa 2 de la MatrizMetaloproteinasa 9 de la MatrizHemoglobina A GlucosiladaInhibidores Tisulares de MetaloproteinasasReceptor Toll-Like 2Diabetes Mellitus tipo 2Metabolismo de los LípidosReacción en Cadena en Tiempo Real de la PolimerasaHumanosMedical Subject Headings::Chemicals and Drugs::Biological Factors::Biological MarkersMedical Subject Headings::Diseases::Cardiovascular Diseases::Vascular Diseases::Arterial Occlusive Diseases::Arteriosclerosis::AtherosclerosisMedical Subject Headings::Diseases::Cardiovascular Diseases::Heart Diseases::Myocardial IschemiaMedical Subject Headings::Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::InflammationMedical Subject Headings::Diseases::Nutritional and Metabolic Diseases::Metabolic Diseases::Glucose Metabolism Disorders::Diabetes Mellitus::Diabetes Mellitus, Type 2Medical Subject Headings::Diseases::Cardiovascular Diseases::Vascular Diseases::Arterial Occlusive DiseasesMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intracellular Signaling Peptides and Proteins::Cyclin-Dependent Kinase Inhibitor Proteins::Cyclin-Dependent Kinase Inhibitor p21Medical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Multienzyme Complexes::Prostaglandin-Endoperoxide Synthases::Cyclooxygenase 2Medical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Peptide Hydrolases::Endopeptidases::Metalloendopeptidases::Matrix Metalloproteinases::Matrix Metalloproteinases, Secreted::Matrix Metalloproteinase 2Medical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Peptide Hydrolases::Endopeptidases::Metalloendopeptidases::Collagenases::Matrix Metalloproteinase 9Medical Subject Headings::Chemicals and Drugs::Carbohydrates::Glycosides::Hemoglobin A, GlycosylatedMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Tissue Inhibitor of MetalloproteinasesMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, Immunologic::Receptors, Pattern Recognition::Toll-Like Receptors::Toll-Like Receptor 2Medical Subject Headings::Diseases::Nutritional and Metabolic Diseases::Metabolic Diseases::Glucose Metabolism Disorders::Diabetes Mellitus::Diabetes Mellitus, Type 2Medical Subject Headings::Phenomena and Processes::Metabolic Phenomena::Metabolism::Lipid MetabolismMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Nucleic Acid Amplification Techniques::Polymerase Chain Reaction::Real-Time Polymerase Chain ReactionMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humansresearch article22828168open access10.1186/1475-2840-11-861475-2840PMC3461422