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Antiatherogenic Effect of Bisvanillyl-Hydralazone, a New Hydralazine Derivative with Antioxidant, Carbonyl Scavenger, and Antiapoptotic Properties
- Source :
- Antioxidants and Redox Signaling, Antioxidants and Redox Signaling, Mary Ann Liebert, 2011, 14 (11), pp.2093-2106. ⟨10.1089/ars.2010.3321⟩, Antioxidants and Redox Signaling, Mary Ann Liebert, 2011, 14 (11), pp.2093-106. ⟨10.1089/ars.2010.3321⟩, Antioxidants and Redox Signaling, 2011, 14 (11), pp.2093-106. ⟨10.1089/ars.2010.3321⟩
- Publication Year :
- 2011
- Publisher :
- HAL CCSD, 2011.
-
Abstract
- International audience; Reactive oxygen species (ROS) generated within the vascular wall trigger low-density lipoprotein (LDL) oxidation, lipid peroxidation, and carbonyl stress that are involved in atherogenesis. We recently reported that the antihypertensive drug, hydralazine, exhibits carbonyl scavenger and antiatherogenic properties, but only moderate antioxidant activity, so that high concentrations are required for inhibiting LDL oxidation. We aimed to develop agents sharing both antioxidant and carbonyl scavenger properties. We have synthesized a new hydralazine derivative, the bisvanillyl-hydralazone (BVH). BVH strongly inhibited LDL oxidation induced by copper and by human endothelial cells (HMEC-1), and prevented the formation of macrophagic foam cells. BVH reduced both the extracellular generation of ROS (superoxide anion and hydrogen peroxide) induced by oxidized LDL (oxLDL), as well as intracellular oxidative stress and proteasome activation, NFkappaB activation, and oxLDL-mediated proinflammatory signaling. In parallel, BVH prevented the carbonyl stress induced by oxLDL on cellular proteins, and blocked the apoptotic cascade as assessed by the inhibition of Bid cleavage, cytochrome C release, and DEVDase activation. Lastly, BVH prevented atherogenesis and carbonyl stress in apoE(-/-) mice. In conclusion, BVH is the prototype of a new class of antioxidant and carbonyl scavenger agents designed for new therapeutical approaches in atherosclerosis.
- Subjects :
- Male
Antioxidant
Physiology
medicine.medical_treatment
[SDV]Life Sciences [q-bio]
Clinical Biochemistry
Apoptosis
030204 cardiovascular system & hematology
medicine.disease_cause
Biochemistry
Antioxidants
Lipid peroxidation
Protein Carbonylation
chemistry.chemical_compound
Mice
0302 clinical medicine
[CHIM] Chemical Sciences
Hydrogen peroxide
Cells, Cultured
Chemokine CCL2
ComputingMilieux_MISCELLANEOUS
General Environmental Science
Chelating Agents
chemistry.chemical_classification
Mice, Knockout
0303 health sciences
Superoxide
Hydralazine
[SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences
Plaque, Atherosclerotic
3. Good health
Lipoproteins, LDL
lipids (amino acids, peptides, and proteins)
medicine.drug
Bisvanillyl-Hydralazone
Proteasome Endopeptidase Complex
03 medical and health sciences
medicine
Cell Adhesion
[CHIM]Chemical Sciences
Animals
Humans
Molecular Biology
030304 developmental biology
Reactive oxygen species
Antiapoptotic Properties
Guaiacol
Endothelial Cells
Cell Biology
Atherosclerosis
Enzyme Activation
Oxidative Stress
chemistry
Hydralazine Derivative
General Earth and Planetary Sciences
Lipid Peroxidation
Reactive Oxygen Species
Carbonyl Scavenger
Oxidative stress
[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Lipoprotein
Foam Cells
Subjects
Details
- Language :
- English
- ISSN :
- 15230864
- Database :
- OpenAIRE
- Journal :
- Antioxidants and Redox Signaling, Antioxidants and Redox Signaling, Mary Ann Liebert, 2011, 14 (11), pp.2093-2106. ⟨10.1089/ars.2010.3321⟩, Antioxidants and Redox Signaling, Mary Ann Liebert, 2011, 14 (11), pp.2093-106. ⟨10.1089/ars.2010.3321⟩, Antioxidants and Redox Signaling, 2011, 14 (11), pp.2093-106. ⟨10.1089/ars.2010.3321⟩
- Accession number :
- edsair.doi.dedup.....e447e66c3b125cbdd699cd4d67381c2a