HIV protease inhibitors-induced atherosclerosis: prevention by alpha-tocopherol.
Prolonged treatments with inhibitors of human immunodeficiency(HIV)-encoded protease (ARPI) have been reported to induce early atherosclerotic events. Our in vitro study indicates that alpha-tocopherol may prevent drug-induced premature atherosclerosis since it interferes with CD36 scavenger receptor over-expression induced by ritonavir in monocytes. The mechanism of CD36 upregulation by ritonavir involves inhibition of the ubiquitin-proteasome system and alpha-tocopherol is able to normalize proteasome activity. These findings suggest that ARPI combined with early alpha-tocopherol supplementation may decrease the drug-induced atherosclerotic risk.
Munteanu
Adelina
A
Institute of Biochemistry and Molecular Biology, University of Bern, Bühlstrasse 28, 3012 Bern, Switzerland.
Ricciarelli
Roberta
R
Zingg
Jean-Marc
JM
D001161:Arteriosclerosis / Q000139:chemically induced* / Q000517:prevention & control*; D015153:Blotting, Western; D018955:CD36 Antigens / Q000096:biosynthesis / Q000378:metabolism; D045744:Cell Line, Tumor; D002469:Cell Separation; D002784:Cholesterol / Q000378:metabolism; D005434:Flow Cytometry; D017320:HIV Protease Inhibitors / Q000494:pharmacology*; D006801:Humans; D010743:Phospholipids / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019438:Ritonavir / Q000494:pharmacology*; D025801:Ubiquitin / Q000378:metabolism; D015854:Up-Regulation; D014810:Vitamin E / Q000378:metabolism; D024502:alpha-Tocopherol / Q000494:pharmacology*
D018955:CD36 Antigens; D017320:HIV Protease Inhibitors; D010743:Phospholipids; D025801:Ubiquitin; D014810:Vitamin E; D002784:Cholesterol; D046988:Proteasome Endopeptidase Complex; D024502:alpha-Tocopherol; D019438:Ritonavir