Oxysterol incorporation into rat aorta resulting in elastin compositional changes.
The incorporation of dietary cholestan-3 beta,5 alpha,6 beta-triol (triol) into rat thoracic aortic tissue and changes in amino acid composition of the elastin were investigated to identify the cytotoxic properties of the triol. Weanling male Sprague-Dawley rats were fed the following diets for three months: (i) normal chow, (ii) normal chow with 1% (w/w) cholesterol added, or (iii) normal chow with 0.9% (w/w) cholesterol and 0.1% (w/w) triol added. Triol levels in the blood and in the thoracic aortic tissue were measured. Compositional changes of elastin were also determined. After three months on the triol-containing diet, triol was found in the thoracic aorta but was not detected in the blood. Amino acid analyses of the aortic tissue elastin revealed that the proline levels in the triol-fed animals were significantly greater than in the other two diet groups, while the elastin levels of leucine, aspartate, arginine, and phenylalanine decreased significantly. The mechanism for these observed changes induced by triol may reflect alternate splicing of elastin messenger ribonucleic acid (mRNA) resulting in structual changes in the elastin molecule. Dietary triol does contribute to tissue triol content and is associated with aortic elastin compositional changes. How these changes may contribute to the development of cardiovascular disease is not known.
Blankenship
J W
JW
Jerry L. Pettis Memorial Veterans Hospital, Loma Linda, California 92357.
Van Gent
C M
CM
Sandberg
L B
LB
Roos
P J
PJ
Scharffenberg
J A
JA
D000595:Amino Acid Sequence; D000704:Analysis of Variance; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism*; D002777:Cholestanols / Q000378:metabolism*; D002784:Cholesterol / Q000097:blood; D002791:Cholesterol, Dietary / Q000378:metabolism*; D004041:Dietary Fats; D004549:Elastin / Q000235:genetics*; D005091:Exons; D000960:Hypolipidemic Agents / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D014176:Protein Biosynthesis; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011919:Rats, Inbred Strains
D002777:Cholestanols; D002791:Cholesterol, Dietary; D004041:Dietary Fats; D000960:Hypolipidemic Agents; D012333:RNA, Messenger; C000474:cholestane-3,5,6-triol; D004549:Elastin; D002784:Cholesterol