Elastin gene expression during aortic wall remodeling in response to sustained hypertension

Travis Maak

Sponsored by Christopher Zarins

Department of Surgery, Stanford University, Stanford, CAÊ 94305

Summary

Structural remodeling of arteries is largely dependent on hemodynamic stimuli. Arterial extracellular matrix (ECM) remodeling occurs in response to increased blood pressure. The specific role of elastin in the remodeling process is unknown. The purpose of this study is to evaluate the effects of altering wall motion, intralumenal pressure, and tensile stress on elastin.

Elastin remodeling in response to acute, sustained hypertension was studied using a rat mid-thoracic aortic coarctation model. The time course and regional localization of elastin expression was determined in the aorta proximal to the coarctation from 1 day to 8 weeks (nÒ3). At each time point blood pressure, arterial diameter, and arterial thickness were measured. RT-PCR, Western blotting and immunohistochemistry were also conducted.Ê

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The mid-thoracic coarctation produced an acute, sustained 25 percent increase in the mean aortic blood pressure of the coarcted rats (P<0.05 as compared to age-matched controls).Ê Elastin mRNA transcription was elevated at 1 and 3 days but returned to baseline at 1 week and for the remainder of the 8-week period (P<0.004).Ê Elastin expression proximal to the coarctation was unchanged at 24 hours but increased at 3 days and 1 week, after which it returned to normal (P<0.0001).Ê This was confirmed by immunohistochemistry data, which show a rapid increase in and subsequent maintenance of arterial wall thickness due to the stress-induced vascular remodeling. Wall thickness was unchanged at 3 days but increased at 1 week with no further changes during 8-week follow up (P<0.002).

Acute, sustained hypertension induces elastin protein expression and subsequent increase in arterial wall thickness in response to aortic coarctation.Ê Elastin transcription precedes elastin expression at 1 and 3 days, which, in turn, precedes wall thickening and returns to normal after 1 week.Ê The aortic wall thickness increases at 1 week and is maintained during the 2-week ö 8-week period.Ê Thus the coarctation-induced increase in elastin gene expression generates a significant increase in wall thickness.Ê This data demonstrates that elastin plays an important role in aortic wall remodeling in response to high blood pressure.