c-myc activation in early coronary lesions in experimental hypercholesterolemia.
This study tested the hypothesis that c-Myc activation, an oxidation-sensitive transcription factor, and its binding partner Max occurs in coronary arteries of hypercholesterolemic (HC) pigs, and can be attenuated by chronic antioxidant intervention. Coronary arteries were isolated from normal, HC pigs, or HC supplemented with antioxidant vitamins (HC + vitamins). The expression of the c-Myc/Max complex, and its target genes GADD45 and p53, was studied in nonatherosclerotic, early lesions (LL), positively staining for oil-red-O, in adjacent lesion-prone regions (PL), and in healthy segments (HV). The expression of c-Myc and Max in HC was 2- to 3-fold greater in PL, and 4-fold in LL, compared to normal vessels (P < 0.01). The expression of GADD45 was down-regulated, and of p53 increased, in the same regions. These alterations were attenuated in the HC + vitamins. Thus, c-Myc activation is an early atherosclerosis, in both PL and LL coronary arterial regions, and can be blunted by chronic dietary antioxidant intervention.
de Nigris
F
F
Department of Medicine, University of Naples, Naples, 80131, Italy.
Lerman
L O
LO
Rodriguez-Porcel
M
M
De Montis
M P
MP
Lerman
A
A
Napoli
C
C
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology; D050976:Basic-Leucine Zipper Transcription Factors; D015153:Blotting, Western; D002784:Cholesterol / Q000097:blood; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000378:metabolism; D015237:Dinoprost / Q000097:blood; D004359:Drug Therapy, Combination; D006937:Hypercholesterolemia / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D008077:Lipoproteins, LDL / Q000097:blood / Q000187:drug effects; D011506:Proteins / Q000187:drug effects / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000187:drug effects / Q000378:metabolism*; D013552:Swine; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53 / Q000187:drug effects / Q000378:metabolism; D014810:Vitamin E / Q000494:pharmacology; D000097642:GADD45 Proteins
D000975:Antioxidants; D001205:Ascorbic Acid; D050976:Basic-Leucine Zipper Transcription Factors; D002784:Cholesterol; D002791:Cholesterol, Dietary; D004268:DNA-Binding Proteins; D015237:Dinoprost; D047908:Intracellular Signaling Peptides and Proteins; D008077:Lipoproteins, LDL; D011506:Proteins; D016271:Proto-Oncogene Proteins c-myc; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D014810:Vitamin E; D000097642:GADD45 Proteins; C067850:Myc associated factor X