Depending on Their Concentration Oxidized Low Density Lipoproteins Stimulate Extracellular Matrix Synthesis or Induce Apoptosis in Human Coronary Artery Smooth Muscle Cells
-
Max G. Bachem
Abstract
Various lines of evidence indicate that oxidative stress resulting in lipid peroxidation and protein modification is involved in the pathogenesis of atherosclerosis and coronary heart disease. We have investigated the effect of modified (oxidized) low-density lipoproteins (oxLDL) on collagen and fibronectin synthesis in cultured human coronary artery smooth muscle cells (HCA-SMC). As shown by immunofluorescence microscopy and time-resolved fluorescence immunoassay, oxLDL dose-dependently stimulated collagen type I and fibronectin synthesis in cultured HCA-SMC. The effect on matrix synthesis was biphasic, with a maximum effect at concentrations between 1 and 10 μg/ml oxLDL. Higher oxLDL concentrations (>25 μg/ml) were cytotoxic. Beside oxLDL, malondialdehyde-modified LDL also stimulated extracellular matrix synthesis. In the presence of 100 μg/ml ascorbic acid, 25, 50 and 100 μg/ml oxLDL induced apoptosis within 6–8 hours (demonstrated by TUNEL-reaction, annexin-V binding and APO-2.7-expression). Apoptosis was not induced by normal (unmodified) LDL and malondialdehyde-modified LDL. The radical scavengers and antioxidants TROLOX and probucol and the hydrogen peroxide eliminator catalase significantly reduced oxLDL-induced apoptosis. Our results demonstrate that low concentrations of oxLDL are profibrogenic by stimulating extracellular matrix synthesis, whereas higher oxLDL concentrations induce oxidative stress and apoptosis in coronary artery smooth muscle cells. The profibrogenic effect might be relevant in the formation of atherosclerotic plaques, and the proapoptotic effect might contribute to an increased plaque vulnerability.
Copyright (c)1999 by Walter de Gruyter GmbH & Co. KG
Articles in the same Issue
- IFCC/Beckman European Conference 1998 Frontiers in Molecular Basis of Disease: Inflammatory Diseases
- Frontiers in Molecular Basis of Disease: Inflammatory Diseases
- Mechanisms of Antigen Presentation
- How to Extinguish Lymphocyte Activation, Immunotyrosine-Based Inhibition Motif (ITIM)-Bearing Molecules a Solution?
- Association between Reduced Human Leukocyte Antigen (HLA)-DR Expression on Blood Monocytes and Increased Plasma Level of Interleukin-10 in Patients with Severe Burns
- Immunostimulatory CpG Motifs Trigger a T Helper-1 Immune Response to Human Immunodeficiency Virus Type-1 (HIV-1) gp160 Envelope Proteins
- Activation and Regulation of NFκB during Acute Inflammation
- CD 14++ Monocytes, CD14+/CD16+ Subset and Soluble CD14 as Biological Markers of Inflammatory Systemic Diseases and Monitoring Immuno-suppressive Therapy
- A Potential Role of an Intracellular Signaling Defect in Neutrophil Functional Abnormalities and Promotion of Tissue Damage in Patients with Localized Juvenile Periodontitis
- Polymorphonuclear Oxidative Burst after Helicobacter pylori Water Extract Stimulation Is not Influenced by the Cytotoxic Genotype but Indicates Infection and Gastritis Grade
- Flow Cytometry of Cerebrospinal Fluid (CSF) Lymphocytes: Alterations of Blood/CSF Ratios of Lymphocyte Subsets in Inflammation Disorders of Human Central Nervous System (CNS)
- Effects of Oxidized Low Density Lipoprotein, Lipid Mediators and Statins on Vascular Cell Interactions
- Mycophenolic Acid Influences T Helper 2 (Th2) Cytokine Induced Expression of Intercellular Cell Adhesion Molecule -1 (ICAM-1) on Human Endothelial Cells
- Alterations of Endothelial Nucleotide Levels by Mycophenolic Acid Result in Changes of Membrane Glycosylation and E-Selectin Expression
- C-Reactive Protein: Structural Biology and Host Defense Function
- A Novel Acute-Phase Marker: Lipopolysaccharide Binding Protein (LBP)
- Detection of Acute Phase Response and Infection. The Role of Procalcitonin and C-Reactive Protein
- Lactoferrin: A Multifunctional Glycoprotein Involved in the Modulation of the Inflammatory Process
- Annexin V and Phospholipid Metabolism
- Regulation of Leukocyte Trafficking by Lipoxins
- Lipoxin and Aspirin-Triggered 15-epi-Lipoxin Cellular Interactions Anti-Inflammatory Lipid Mediators
- Differentiation and Assessment of Cell Death
- Depending on Their Concentration Oxidized Low Density Lipoproteins Stimulate Extracellular Matrix Synthesis or Induce Apoptosis in Human Coronary Artery Smooth Muscle Cells
- Apheresis of Plasma Compounds as a Therapeutic Principle in Severe Sepsis and Multiorgan Dysfunction Syndrome
- Supportive Therapy of the Sepsis Syndrome
- Supplemental Immune Globulins in Sepsis
- Polymorphonuclear Granulocyte Stimulation by Cellulose-Based Hemodialysis Membranes
- Reduction of Circulating Cholesterol and Apolipoprotein Levels during Sepsis
- Outcome Prediction by Traditional and New Markers of Inflammation in Patients with Sepsis
- Isolation of Highly Enriched Human Monocytes from Ten ml Samples of Heparinised Whole Blood
- Endotoxin Adsorbant Based on Immobilized Human Serum Albumin
Articles in the same Issue
- IFCC/Beckman European Conference 1998 Frontiers in Molecular Basis of Disease: Inflammatory Diseases
- Frontiers in Molecular Basis of Disease: Inflammatory Diseases
- Mechanisms of Antigen Presentation
- How to Extinguish Lymphocyte Activation, Immunotyrosine-Based Inhibition Motif (ITIM)-Bearing Molecules a Solution?
- Association between Reduced Human Leukocyte Antigen (HLA)-DR Expression on Blood Monocytes and Increased Plasma Level of Interleukin-10 in Patients with Severe Burns
- Immunostimulatory CpG Motifs Trigger a T Helper-1 Immune Response to Human Immunodeficiency Virus Type-1 (HIV-1) gp160 Envelope Proteins
- Activation and Regulation of NFκB during Acute Inflammation
- CD 14++ Monocytes, CD14+/CD16+ Subset and Soluble CD14 as Biological Markers of Inflammatory Systemic Diseases and Monitoring Immuno-suppressive Therapy
- A Potential Role of an Intracellular Signaling Defect in Neutrophil Functional Abnormalities and Promotion of Tissue Damage in Patients with Localized Juvenile Periodontitis
- Polymorphonuclear Oxidative Burst after Helicobacter pylori Water Extract Stimulation Is not Influenced by the Cytotoxic Genotype but Indicates Infection and Gastritis Grade
- Flow Cytometry of Cerebrospinal Fluid (CSF) Lymphocytes: Alterations of Blood/CSF Ratios of Lymphocyte Subsets in Inflammation Disorders of Human Central Nervous System (CNS)
- Effects of Oxidized Low Density Lipoprotein, Lipid Mediators and Statins on Vascular Cell Interactions
- Mycophenolic Acid Influences T Helper 2 (Th2) Cytokine Induced Expression of Intercellular Cell Adhesion Molecule -1 (ICAM-1) on Human Endothelial Cells
- Alterations of Endothelial Nucleotide Levels by Mycophenolic Acid Result in Changes of Membrane Glycosylation and E-Selectin Expression
- C-Reactive Protein: Structural Biology and Host Defense Function
- A Novel Acute-Phase Marker: Lipopolysaccharide Binding Protein (LBP)
- Detection of Acute Phase Response and Infection. The Role of Procalcitonin and C-Reactive Protein
- Lactoferrin: A Multifunctional Glycoprotein Involved in the Modulation of the Inflammatory Process
- Annexin V and Phospholipid Metabolism
- Regulation of Leukocyte Trafficking by Lipoxins
- Lipoxin and Aspirin-Triggered 15-epi-Lipoxin Cellular Interactions Anti-Inflammatory Lipid Mediators
- Differentiation and Assessment of Cell Death
- Depending on Their Concentration Oxidized Low Density Lipoproteins Stimulate Extracellular Matrix Synthesis or Induce Apoptosis in Human Coronary Artery Smooth Muscle Cells
- Apheresis of Plasma Compounds as a Therapeutic Principle in Severe Sepsis and Multiorgan Dysfunction Syndrome
- Supportive Therapy of the Sepsis Syndrome
- Supplemental Immune Globulins in Sepsis
- Polymorphonuclear Granulocyte Stimulation by Cellulose-Based Hemodialysis Membranes
- Reduction of Circulating Cholesterol and Apolipoprotein Levels during Sepsis
- Outcome Prediction by Traditional and New Markers of Inflammation in Patients with Sepsis
- Isolation of Highly Enriched Human Monocytes from Ten ml Samples of Heparinised Whole Blood
- Endotoxin Adsorbant Based on Immobilized Human Serum Albumin
