Calcium-channel blockers inhibit human low density lipoprotein oxidation by oxygen radicals

Claudio Napoli, Massimo Chiariello, Giuseppe Palumbo, Giuseppe Ambrosio

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Previous studies have shown that calcium channel blockers may reduce the development of experimental atherosclerosis, and that nifedipine may slow the progression of coronary atherosclerosis in humans. The mechanisms responsible for this antiatherogenic effect are still unclear. It has been recently proposed that oxygen free radicals can induce the oxidation of human low-density lipoproteins (LDL) and that oxidized LDL may be an atherogenic stimulus. Previous studies in other systems have shown that calcium channel blockers may effectively inhibit oxygen radical-induced lipid peroxidation in vitro. Thus, the aim of the present study was to investigate whether calcium channel blockers may also reduce LDL modifications induced by oxygen radicals. Isolated human LDL were exposed to oxygen radicals generated by CuSO4 (10 μM for 18 hours) after a 30 minute preincubation with different concentrations (1-100 μM) of nifedipine, diltiazem, and verapamil. Lipid peroxidation was measured from malonyldihaldehyde (MDA) production. Oxygen radical-induced damage on apolipoprotein-B100 was evaluated by acrylamide and agarose gel electrophoresis. Calcium channel blockers dose-dependently prevented oxidation of both the lipid and protein components of LDL. MDA formation was reduced in LDL pre-incubated with calcium antagonists before exposure to oxygen radicals (% MDA inhibition was 89.8 ± 6.9 with 30 μM nifedipine, 68.6 ± 4.9 with 30 μM verapamil, and 68.6 ± 7.1 with 30 μM diltiazem; p <0.01 vs. controls). Similarly, apolipoprotein-B100 integrity was preserved against oxygen radical attack in the presence of calcium antagonists. Thus, calcium channel blockers reduce the oxidation of human LDL in vitro. These data suggest that reduced formation of atherogenic oxidized LDL may be an additional mechanism for the antiatherosclerotic effects of calcium channel blockers in vivo.

Original languageEnglish
Pages (from-to)417-424
Number of pages8
JournalCardiovascular Drugs and Therapy
Volume10
Issue number4
DOIs
Publication statusPublished - 1996

Fingerprint

Calcium Channel Blockers
LDL Lipoproteins
Reactive Oxygen Species
Nifedipine
Diltiazem
Apolipoproteins
Verapamil
Lipid Peroxidation
Calcium
Agar Gel Electrophoresis
Acrylamide
Free Radicals
Coronary Artery Disease
Atherosclerosis
Lipids
Proteins

Keywords

  • Atherosclerosis
  • Calcium channel-blockers
  • Low density lipoprotein
  • Oxygen radicals
  • Peroxidation

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Cardiology and Cardiovascular Medicine
  • Pharmacology

Cite this

Calcium-channel blockers inhibit human low density lipoprotein oxidation by oxygen radicals. / Napoli, Claudio; Chiariello, Massimo; Palumbo, Giuseppe; Ambrosio, Giuseppe.

In: Cardiovascular Drugs and Therapy, Vol. 10, No. 4, 1996, p. 417-424.

Research output: Contribution to journalArticle

Napoli, Claudio ; Chiariello, Massimo ; Palumbo, Giuseppe ; Ambrosio, Giuseppe. / Calcium-channel blockers inhibit human low density lipoprotein oxidation by oxygen radicals. In: Cardiovascular Drugs and Therapy. 1996 ; Vol. 10, No. 4. pp. 417-424.
@article{5ac4f1abd4f24eee842f6e4e6f75c957,
title = "Calcium-channel blockers inhibit human low density lipoprotein oxidation by oxygen radicals",
abstract = "Previous studies have shown that calcium channel blockers may reduce the development of experimental atherosclerosis, and that nifedipine may slow the progression of coronary atherosclerosis in humans. The mechanisms responsible for this antiatherogenic effect are still unclear. It has been recently proposed that oxygen free radicals can induce the oxidation of human low-density lipoproteins (LDL) and that oxidized LDL may be an atherogenic stimulus. Previous studies in other systems have shown that calcium channel blockers may effectively inhibit oxygen radical-induced lipid peroxidation in vitro. Thus, the aim of the present study was to investigate whether calcium channel blockers may also reduce LDL modifications induced by oxygen radicals. Isolated human LDL were exposed to oxygen radicals generated by CuSO4 (10 μM for 18 hours) after a 30 minute preincubation with different concentrations (1-100 μM) of nifedipine, diltiazem, and verapamil. Lipid peroxidation was measured from malonyldihaldehyde (MDA) production. Oxygen radical-induced damage on apolipoprotein-B100 was evaluated by acrylamide and agarose gel electrophoresis. Calcium channel blockers dose-dependently prevented oxidation of both the lipid and protein components of LDL. MDA formation was reduced in LDL pre-incubated with calcium antagonists before exposure to oxygen radicals ({\%} MDA inhibition was 89.8 ± 6.9 with 30 μM nifedipine, 68.6 ± 4.9 with 30 μM verapamil, and 68.6 ± 7.1 with 30 μM diltiazem; p <0.01 vs. controls). Similarly, apolipoprotein-B100 integrity was preserved against oxygen radical attack in the presence of calcium antagonists. Thus, calcium channel blockers reduce the oxidation of human LDL in vitro. These data suggest that reduced formation of atherogenic oxidized LDL may be an additional mechanism for the antiatherosclerotic effects of calcium channel blockers in vivo.",
keywords = "Atherosclerosis, Calcium channel-blockers, Low density lipoprotein, Oxygen radicals, Peroxidation",
author = "Claudio Napoli and Massimo Chiariello and Giuseppe Palumbo and Giuseppe Ambrosio",
year = "1996",
doi = "10.1007/BF00051106",
language = "English",
volume = "10",
pages = "417--424",
journal = "Cardiovascular Drugs and Therapy",
issn = "0920-3206",
publisher = "Kluwer Academic Publishers",
number = "4",

}

TY - JOUR

T1 - Calcium-channel blockers inhibit human low density lipoprotein oxidation by oxygen radicals

AU - Napoli, Claudio

AU - Chiariello, Massimo

AU - Palumbo, Giuseppe

AU - Ambrosio, Giuseppe

PY - 1996

Y1 - 1996

N2 - Previous studies have shown that calcium channel blockers may reduce the development of experimental atherosclerosis, and that nifedipine may slow the progression of coronary atherosclerosis in humans. The mechanisms responsible for this antiatherogenic effect are still unclear. It has been recently proposed that oxygen free radicals can induce the oxidation of human low-density lipoproteins (LDL) and that oxidized LDL may be an atherogenic stimulus. Previous studies in other systems have shown that calcium channel blockers may effectively inhibit oxygen radical-induced lipid peroxidation in vitro. Thus, the aim of the present study was to investigate whether calcium channel blockers may also reduce LDL modifications induced by oxygen radicals. Isolated human LDL were exposed to oxygen radicals generated by CuSO4 (10 μM for 18 hours) after a 30 minute preincubation with different concentrations (1-100 μM) of nifedipine, diltiazem, and verapamil. Lipid peroxidation was measured from malonyldihaldehyde (MDA) production. Oxygen radical-induced damage on apolipoprotein-B100 was evaluated by acrylamide and agarose gel electrophoresis. Calcium channel blockers dose-dependently prevented oxidation of both the lipid and protein components of LDL. MDA formation was reduced in LDL pre-incubated with calcium antagonists before exposure to oxygen radicals (% MDA inhibition was 89.8 ± 6.9 with 30 μM nifedipine, 68.6 ± 4.9 with 30 μM verapamil, and 68.6 ± 7.1 with 30 μM diltiazem; p <0.01 vs. controls). Similarly, apolipoprotein-B100 integrity was preserved against oxygen radical attack in the presence of calcium antagonists. Thus, calcium channel blockers reduce the oxidation of human LDL in vitro. These data suggest that reduced formation of atherogenic oxidized LDL may be an additional mechanism for the antiatherosclerotic effects of calcium channel blockers in vivo.

AB - Previous studies have shown that calcium channel blockers may reduce the development of experimental atherosclerosis, and that nifedipine may slow the progression of coronary atherosclerosis in humans. The mechanisms responsible for this antiatherogenic effect are still unclear. It has been recently proposed that oxygen free radicals can induce the oxidation of human low-density lipoproteins (LDL) and that oxidized LDL may be an atherogenic stimulus. Previous studies in other systems have shown that calcium channel blockers may effectively inhibit oxygen radical-induced lipid peroxidation in vitro. Thus, the aim of the present study was to investigate whether calcium channel blockers may also reduce LDL modifications induced by oxygen radicals. Isolated human LDL were exposed to oxygen radicals generated by CuSO4 (10 μM for 18 hours) after a 30 minute preincubation with different concentrations (1-100 μM) of nifedipine, diltiazem, and verapamil. Lipid peroxidation was measured from malonyldihaldehyde (MDA) production. Oxygen radical-induced damage on apolipoprotein-B100 was evaluated by acrylamide and agarose gel electrophoresis. Calcium channel blockers dose-dependently prevented oxidation of both the lipid and protein components of LDL. MDA formation was reduced in LDL pre-incubated with calcium antagonists before exposure to oxygen radicals (% MDA inhibition was 89.8 ± 6.9 with 30 μM nifedipine, 68.6 ± 4.9 with 30 μM verapamil, and 68.6 ± 7.1 with 30 μM diltiazem; p <0.01 vs. controls). Similarly, apolipoprotein-B100 integrity was preserved against oxygen radical attack in the presence of calcium antagonists. Thus, calcium channel blockers reduce the oxidation of human LDL in vitro. These data suggest that reduced formation of atherogenic oxidized LDL may be an additional mechanism for the antiatherosclerotic effects of calcium channel blockers in vivo.

KW - Atherosclerosis

KW - Calcium channel-blockers

KW - Low density lipoprotein

KW - Oxygen radicals

KW - Peroxidation

UR - http://www.scopus.com/inward/record.url?scp=0029860461&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029860461&partnerID=8YFLogxK

U2 - 10.1007/BF00051106

DO - 10.1007/BF00051106

M3 - Article

C2 - 8924055

AN - SCOPUS:0029860461

VL - 10

SP - 417

EP - 424

JO - Cardiovascular Drugs and Therapy

JF - Cardiovascular Drugs and Therapy

SN - 0920-3206

IS - 4

ER -