Tissue microarray detection of matrix metalloproteinases, in diseased tricuspid and bicuspid aortic valves with or without pathology of the ascending aorta.
OBJECTIVE
The degeneration of bicuspid aortic valve and its frequent association with ascending aortic pathology, point to a still unidentified genetic tissue defect with unknown mediators. Metalloproteinases (MMPs) are lytic enzymes that have been strongly implicated in aneurysm formation. The purpose of this study was to detect the presence of these enzymes in aortic valvular tissue in healthy and diseased aortic valves with or without the presence of synchronous ascending aortic pathology.


METHODS
Aortic valve specimens from 26 aortic valve replacement patients as well as 4 healthy control tricuspid aortic valves were included. 10 patients had bicuspid aortic valves, and 16 had tricuspid aortic valves. Half of our patient population had a concomitant aortic procedure for aortic pathology. The study detected MMPs 1,2 and 9 as well as their Tissue inhibitors (TIMPs) 1 and 2. MMP and TIMP detection was accomplished with the construction of a tissue micro array and immunohistochemistry.


CONCLUSIONS
MMP-9 expression was significantly higher in bicuspid aortic valves compared to normal valves (P<0.05). When compared to the tricuspid valve group, MMP-9 mean value was significantly higher in bicuspid valves (P<0.05). When the entire rest of the valve group (n=4+16, i.e. control and tricuspid valve groups) was compared to the bicuspid valve group, bicuspid valves had significantly higher MMP-2, and MMP-9 (P<0.01) expression. TIMP expression also changed in diseased valves, among different patient groups. This increased proteolytic presence in bicuspid aortic valves may attribute to the observed decreased elastin and collagen content, and their resultant functional failure.
Koullias
George J
GJ
Section of Cardiothoracic Surgery, Yale New Haven Hospital, New Haven, CT, USA. kouillas@hotmail.com
Korkolis
Dimitris P
DP
Ravichandran
Pars
P
Psyrri
Amanda
A
Hatzaras
Ioannis
I
Elefteriades
John A
JA
D001014:Aortic Aneurysm / Q000201:enzymology* / Q000473:pathology; D001022:Aortic Valve Insufficiency / Q000201:enzymology* / Q000473:pathology; D001024:Aortic Valve Stenosis / Q000201:enzymology* / Q000473:pathology; D006330:Heart Defects, Congenital / Q000201:enzymology / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D020782:Matrix Metalloproteinases / Q000032:analysis*; D008943:Mitral Valve / Q000201:enzymology / Q000473:pathology; D018709:Statistics, Nonparametric; D046888:Tissue Array Analysis / Q000379:methods*; D014261:Tricuspid Valve / Q000201:enzymology / Q000473:pathology
D020782:Matrix Metalloproteinases