title: Captopril inhibits the oxidative modification of apolipoprotein B-100 caused by myeloperoxydase in a comparative in vitro assay of angiotensin converting enzyme inhibitors.
abstract: The oxidative modification of low-density lipoproteins (LDL) is a key event in the formation of atheromatous lesions. Indeed, oxidized derivatives accumulate in the vascular wall and promote a local inflammatory process which triggers the progression of the atheromatous plaque. Myeloperoxidase (MPO) has been mentioned as a major contributor to this oxidative process. It takes part in the oxidation both of lipids by chlorination and peroxidation and of apolipoprotein B-100. Based on recent observations with several anti-inflammatory and thiol-containing drugs, the present study was designed to test the hypothesis that anti-hypertensive agents from the angiotensin converting enzyme (ACE) inhibitors group inhibit the oxidative modifications of Apo B-100 caused by MPO. Captopril, ramipril, enalapril, lisinopril and fosinopril were assessed by measuring: their inhibiting effect on the MPO/H(2)O(2)/Cl(-) system, the accumulation of compound II, which reflects the inhibition of the synthesis of HOCl and the LDL oxidation by MPO in presence of several concentrations of ACE inhibitors. Only captopril, a thiol-containing ACE inhibitor, was able to significantly decrease the oxidative modification of LDL in a dose dependent manner and this by scavenging HOCl. This efficient anti-hypertensive drug therefore appears to also protect against the atherosclerotic process by this newly documented mechanism.
authors.affiliation: Laboratory of Pharmaceutical Chemistry, Institute of Pharmacy, Université Libre de Bruxelles, Campus Plaine 205-5, B-1050 Brussels, Belgium.
authors.forename: Pierre
authors.initials: P
authors.lastname: Van Antwerpen
authors.forename: Ilham
authors.initials: I
authors.lastname: Legssyer
authors.forename: Karim
authors.initials: K
authors.lastname: Zouaoui Boudjeltia
authors.forename: Sajida
authors.initials: S
authors.lastname: Babar
authors.forename: Patrick
authors.initials: P
authors.lastname: Moreau
authors.forename: Nicole
authors.initials: N
authors.lastname: Moguilevsky
authors.forename: Michel
authors.initials: M
authors.lastname: Vanhaeverbeek
authors.forename: Jean
authors.initials: J
authors.lastname: Ducobu
authors.forename: Jean
authors.initials: J
authors.lastname: Nève
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000959:Antihypertensive Agents / Q000494:pharmacology*; D053299:Apolipoprotein B-100; D001055:Apolipoproteins B / Q000378:metabolism*; D050197:Atherosclerosis / Q000517:prevention & control; D002216:Captopril / Q000494:pharmacology*; D004656:Enalapril / Q000494:pharmacology; D017328:Fosinopril / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D006997:Hypochlorous Acid / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism*; D017706:Lisinopril / Q000494:pharmacology; D010084:Oxidation-Reduction; D009195:Peroxidase / Q000378:metabolism; D017257:Ramipril / Q000494:pharmacology; D011994:Recombinant Proteins / Q000378:metabolism
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D053299:Apolipoprotein B-100; D001055:Apolipoproteins B; D008077:Lipoproteins, LDL; D011994:Recombinant Proteins; D004656:Enalapril; D006997:Hypochlorous Acid; D002216:Captopril; D006861:Hydrogen Peroxide; D017706:Lisinopril; D009195:Peroxidase; D017257:Ramipril; D017328:Fosinopril