Biphasic response of tropoelastin at the poststenotic dilation segment of the rabbit aorta.
OBJECTIVE
The purpose of this study was to assess the time course of tropoelastin gene expression in the poststenotic dilatation segment of rabbit aorta with experimental coarctation.


METHODS
Midthoracic aortic coarctation was created in rabbits to produce a PSD. The time points of the study after coarctation were 1, 3, and 7 days and 2, 4, and 8 weeks (n = 3 each). Additional animals (n = 6) were subjected to hypercholesterolemia for analysis of tropoelastin expression in intimal lesions. Northern and Western blot analyses were used to quantitate tropoelastin messenger RNA (mRNA) and protein, and immunohistochemistry was used to analyze tropoelastin distribution.


RESULTS
Thoracic aortic coarctation produced a moderate stenosis, which resulted in PSD. mRNA levels in the PSD segment decreased at days 1 and 3, followed by an increase at 2 and 4 weeks (P <.05 versus controls). This biphasic change in tropoelastin mRNA was associated with increase in tropoelastin protein levels at 2 and 4 weeks (P <.05 versus controls). PSD diameter reached a maximum at 4 weeks and did not increase significantly thereafter. The number of medial elastic laminae in PSD was reduced slightly, but media thickness was unchanged. Intimal lesions were much smaller in the PSD segment than in the proximal segment in animals with hypertension superimposed with hypercholesterolemia. Moreover, tropoelastin protein distributed not only in the intima but also in the media of the PSD.


CONCLUSIONS
Tropoelastin gene expression is regulated in a biphasic pattern and precedes PSD formation. The differential distribution of tropoelastin in the media suggests a role for tropoelastin in the poststenotic adaptation response, which may provide increased elasticity to the PSD wall.
Xu
Chengpei
C
Department of Surgery, Stanford University, CA 94305, USA. cx11@stanford.edu
Zarins
Christopher K
CK
Glagov
Seymour
S
D000818:Animals; D001017:Aortic Coarctation / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D001024:Aortic Valve Stenosis / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D002404:Catheterization; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000473:pathology; D015870:Gene Expression / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D011817:Rabbits; D011930:Reaction Time; D013997:Time Factors; D014333:Tropoelastin / Q000235:genetics*
D014333:Tropoelastin