Hypertension accelerated experimental abdominal aortic aneurysm through upregulation of nuclear factor κB and Ets

Abstract

Conclusion: Hypertension accelerates progression of experimental abdominal aortic aneurysms (AAAs) by upregulation of Ets and nuclear factor κB (NF κB). Summary: The pathogenesis of AAA is complex but appears to involve upregulation of certain matrix metalloproteinases (MMPs). Experimental AAAs are characterized by upregulation of transcription factors, NF κB, which regulate transcription, and Ets, which regulates expression of MMPs. The role of hypertension in pathogenesis of AAA is controversial, with some studies suggesting it contributes to aneurysm formation and other studies suggesting it is not an independent risk factor for aneurysm formation. In this study, the authors used an experimental model of AAA to investigate the effects of hypertension on transcription factors NF κB and Ets. They also investigated the effects of hypertension on progression of AAA. Experimental AAAs were produced by elastase perfusion in both normotensive and hypertensive rats. Compared with normotensive rats, the size of the AAAs increased more rapidly in the hypertensive rats. Western blot analysis indicated the expression of MMP-2, MMP-3, MMP-9, and MMP-12, as well as that of intercellular adhesion molecule, was increased in hypertensive rats. This was accompanied by upregulation of NFκB and Ets. There was also increased activity of MMPs in the aortas of hypertensive rats vs those of normotensive rats. Chimeric decoy oligodeoxynucleotide (ODN) inhibits expression of NFκB and Ets. Transfection of the ODN resulted in significant inhibition of aortic dilatation in both hypertensive and normotensive rats. Transfection with chimeric decoy ODN resulted in significant inhibition of degeneration of elastic fibers in aortas of both normotensive and hypertensive rats. Expression of MMP-2, MMP-3, MMP-9, and MMP-12 and intercellular adhesion molecule was decreased by chimeric decoy ODN. This was accompanied by inhibition of macrophage migration. Comment: The study indicates hypertension accelerates progression of AAA in an experimental rat model. Perhaps inhibition of NF κB and Ets may someday be used as a method of decreasing aneurysm expansion in both normotensive and hypertensive patients.