Matrix metalloproteinase 14 and 19 expression is associated with thoracic aortic aneurysms

• Published in: The Journal of thoracic and cardiovascular surgery Vol. 144; no. 2; pp. 459 - 466
• Main Authors: Jackson, Veronica, MD, Olsson, Therese, BMA, Kurtovic, Sanela, PhD, Folkersen, Lasse, MSc, Paloschi, Valentina, MSc, Wågsäter, Dick, PhD, Franco-Cereceda, Anders, MD, PhD, Eriksson, Per, PhD
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01.08.2012; Elsevier
• Subjects: Aged; Aged, 80 and over; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Aortic Aneurysm, Thoracic - metabolism; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Cardiothoracic Surgery; Diseases of the aorta; Female; Humans; Immunohistochemistry; Male; Matrix Metalloproteinase 14 - metabolism; Matrix Metalloproteinase Inhibitors; Matrix Metalloproteinases - metabolism; Matrix Metalloproteinases, Secreted - metabolism; Medical sciences; Medicin och hälsovetenskap; Microarray Analysis; Middle Aged; Pneumology; Real-Time Polymerase Chain Reaction; RNA, Messenger - metabolism; tricuspid aortic valve; ribonucleic acid; RNA; 29; TAV; mRNA; principal component; principal components analysis; 26.1; thoracic aortic aneurysm; tissue inhibitors of metalloproteinase; messenger ribonucleic acid; polymerase chain reaction; 35; smooth muscle cell; 18; SMC; PCA; MMP; PC; bicuspid aortic valve; TAA; BAV; matrix metalloproteinase; PCR; TIMP; Cardiovascular disease; Anesthesia; Metalloproteinase; Thorax; Circulatory system; Cardiology; Gene expression; Aortic aneurysm
• ISSN: 0022-5223; 1097-685X; 1097-685X
• DOI: 10.1016/j.jtcvs.2011.08.043

Objective It is hypothesized that an altered turnover of extracellular matrix mediated by matrix metalloproteinases (MMPs) is present in thoracic aortic aneurysms. Here, we analyzed the occurrence of MMPs and MMP inhibitors in ascending aortic aneurysms in patients with bicuspid and tricuspid aortic valves. Methods Expression of 23 MMPs and their inhibitors was measured in aortic intima/media and adventitia in 109 patients (40 tricuspid, 69 bicuspid, 68 with aortic diameter ≥ 4.5 cm, and 41 with ≤ 4.0 cm) using Affymetrix Exon arrays (Affymetrix, Santa Clara, Calif). Gene expression was confirmed by quantitative real-time polymerase chain reaction. Principal components analysis was used to study differences in gene expression. Immunohistochemistry was used to study protein expression. Results We detected messenger RNA expression for gelatinases (MMP2 and MMP9), stromelysin 3 (MMP11), all membrane bound MMPs (MMP14, MMP15, MMP16, MMP17, MMP24, MMP25), MMP19, MMP21, and MMP28 in ascending aorta. No expression of collagenases was detected. Principal components analysis showed that changes in mRNA expression between dilated and nondilated aorta were mainly detected in patients with tricuspid aortic valves. MMP14 and MMP19 showed higher expression in dilated aortas and MMP19 expression correlated positively to maximal aortic diameter in patients with tricuspid aortic valves (Rho = 0.61, P  = .004, and Rho = 0.57, P  = .008, using raw and body surface area–corrected aortic diameter, respectively). Immunohistochemical staining demonstrated increased medial expression of MMP14 and MMP19 in dilated aorta. Conclusions The present study identifies MMP14 and MMP19 as proteolytic enzymes potentially involved in aneurysm formation in the ascending aorta of patients with tricuspid aortic valves.