Cholesterol feeding modulates spatial expression of TGF-beta 1 and beta 2 in aortas of Watanabe rabbits.
Several cytokines have been identified as markers of early atherosclerotic disease during vascular injury and remodelling. Of particular importance, transforming growth factor-beta (TGF-beta 1) has been found to be crucial in promoting connective tissue deposition resulting in both intimal and medial hyperplasia. However, the expression of TGF-beta 1 and beta 2 during cholesterol feeding in the Watanabe rabbit, an established model of hypercholesterolemia, has not been evaluated. Accordingly, we examined the expression of TGF-beta 1 and beta 2 signal from aortic segments of 10 heterozygous Watanabe rabbits with the use of reverse transcription-polymerase chain reaction (RT-PCR) amplification during normal non-supplemental diet and during 0.5% supplemental cholesterol feeding for a period of two months. TGF-beta transcripts from the aortic tissue were quantified at the end of the feeding interval. For Watanabe rabbits fed regular chow, the expression of both TGF-beta 1 and beta 2 is reduced in the aortic arch as compared with the descending aorta. In contrast, Watanabe rabbits fed high cholesterol diets manifested a differential expression of TGF-beta isoforms depending on the spatial location within the aorta. In the aortic arch, increased transcript signals for both TGF-beta 1 and beta 2 were noted as compared with rabbits on normal chow. The lesions found in the aortic arch are typified by abundant foam cells and proliferating smooth muscle cells. Analysis of the TGF-beta 1 and 2 profile on these same cell elements in vitro results in a similar expression of increased mRNA isoforms for TGF-beta 1 and 2.(ABSTRACT TRUNCATED AT 250 WORDS)
López-Candales
A
A
Department of Medicine, Jewish Hospital of St. Louis, Washington University School of Medicine, MO 63110, USA.
Scott
M J
MJ
Wickline
S A
SA
D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology / Q000378:metabolism; D001483:Base Sequence; D002478:Cells, Cultured; D002791:Cholesterol, Dietary / Q000494:pharmacology*; D004036:Diet, Atherogenic; D004195:Disease Models, Animal; D006937:Hypercholesterolemia / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D016133:Polymerase Chain Reaction / Q000379:methods; D011817:Rabbits; D051381:Rats; D012995:Solubility; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*
D002791:Cholesterol, Dietary; D016212:Transforming Growth Factor beta