Aortic Dilatation With Bicuspid Aortic Valves: Cusp Fusion Correlates to Matrix Metalloproteinases and Inhibitors

Abstract

Background Congenital bicuspid aortic valves (BAVs) result from fusion of two valve cusps, resulting in left-noncoronary (L-N), right-left (R-L), and right-noncoronary (R-N) morphologies. BAVs predispose to ascending thoracic aortic aneurysms (ATAAs). This study hypothesized that ATAAs with each BAV morphology group possess unique signatures of matrix metalloproteinases (MMPs) and endogenous tissue inhibitors (TIMPs). Methods ATAA tissue from 46 BAV patients was examined for MMP/TIMP abundance and global MMP activity compared to normal aortic specimens (n=15). Proteolytic balance was calculated as the ratio of MMP abundance to a composite TIMP score (TS). Results were stratified by valve morphology group (L-N (n=6), R-L (n=31), and R-N(n=9)). Results The BAV specimens (p<0.05 vs. normal aorta, 100%) displayed elevated global MMP activity (273±63%), MMP-9 (263±47%), and decreased MMP -7 (56±10%), -8 (58±11%), TIMP -1 (63±7%) and -4 (38±3%). The R-L group showed increased global MMP activity (286±89%) and MMP-9 (267±55%) with reduced MMP -7 (45±7%) -8 (68±15%), TIMP -1 (58±7%) and -4 (35±3%). The L-N group showed elevated global MMP activity (284±71%), and decreased MMP-8 (37±17%) and TIMP-4 (48±14). In the R-N group, MMP -7 (46±13%) and -8 (36±17%), and TIMP -1 (59±10) and -4 (42±5%) were decreased. The R-L group demonstrated an increased proteolytic balance for MMP-1, MMP-9, and MMP-12 relative to L-N and R-N. Conclusion Each BAV morphology group possesses a unique signature of MMPs and TIMPs. MMP/TIMP score ratios suggest that the R-L group may be more aggressive, justifying earlier surgical intervention.

Polymorphisms of Matrix Metalloproteases 2 and 9 Genes in Ascending Aorta Aneurism Patients

“…В одной из работ Ikonomidis JS, et al выявлены различия в степени повышения содержания и актив-ности матриксных металлопротеиназ (ММП) в стенке аорты у пациентов с БАК в зависимости от того, какие створки аортального клапана срослись [10]. Вместе с тем, открытым остается вопрос, с чем свя-заны различия в профиле ММП: с генетическими особенностями, которые приводят к разным типам сращений, или отличиями в биомеханике клапанов с неодинаковой конфигурацией и, соответственно, разным ударом о стенку сосуда?…”

Current Topics on Bicuspid Aortic Valve: Clinical Aspects and Surgical Management

“…This phenomenon may be more aggressive in BAV-associated ascending aorta dilatation in the right-left fusion type, and, thus, requires earlier surgical intervention. 14) The combination of mitral regurgitation due to myxomatous degeneration and BAV is sometimes recognized as having a large prolapsing anterior leaflet of the mitral valve and dilated aortic annulus with aortic insufficiency due to cusp prolapse. Toronto's group reported that 1.8% of patients with BAV had anterior leaflet disease of the mitral valve.…”

Circulating Soluble Receptor for Advanced Glycation End Product Identifies Patients With Bicuspid Aortic Valve and Associated Aortopathies

“…However, the optimal timing of aortic surgery in thoracic aortic aneurysm patients remains uncertain for patients with both BAV and TAV. 1,2,[4][5][6][7][8]10,[12][13][14]16 In a recent study, we showed that >60% of patients with acute aortic dissection presented with aortic diameters smaller than those indicated for surgery. 1,2,[5][6][7][8]10,[12][13][14][16][17][18][19] Therefore, the current indications for elective surgical intervention are imperfect predictors of aortic dissection and rupture, especially for patients with BAV.…”

“…1,2,[4][5][6][7][8]10,[12][13][14]16 In a recent study, we showed that >60% of patients with acute aortic dissection presented with aortic diameters smaller than those indicated for surgery. 1,2,[5][6][7][8]10,[12][13][14][16][17][18][19] Therefore, the current indications for elective surgical intervention are imperfect predictors of aortic dissection and rupture, especially for patients with BAV. 1,2,[4][5][6][7][8]10,12,16,20 Also, of concern is the common development of subsequent ascending aortopathies in patients who have had previous AVR for BAV in the near or remote past.…”

“…[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] The presence of a BAV is associated with frequent and premature valve dysfunction, such as aortic stenosis (AS) and aortic insufficiency (AI). [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] In patients <50 years of age having aortic valve replacement (AVR) for severe AS, virtually all of them have BAV. Until the age of 70 years, patients with BAV outnumber those with tricuspid aortic valve (TAV) having AVR for AS and not until the age of >80 years do patients with TAV predominate.…”