Size matters : The relationship between MMP-9 expression and aortic diameter

• Published in: Circulation (New York, N.Y.) Vol. 96; no. 7; pp. 2228 - 2232
• Main Authors: MCMILLAN, W. D, TAMARINA, N. A, CIPOLLONE, M, JOHNSON, D. A, PARKER, M. A, PEARCE, W. H
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 07.10.1997
• Subjects: Aged; Aorta, Abdominal - anatomy & histology; Aorta, Abdominal - enzymology; Aorta, Abdominal - pathology; Aortic Aneurysm, Abdominal - enzymology; Aortic Aneurysm, Abdominal - pathology; Aortic Aneurysm, Abdominal - surgery; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Collagenases - biosynthesis; Diabetic Angiopathies; Diseases of the aorta; DNA, Complementary; Female; Humans; Male; Matrix Metalloproteinase 9; Medical sciences; Middle Aged; Polymerase Chain Reaction; Reference Values; RNA, Messenger - biosynthesis; Smoking; Transcription, Genetic; Arterial disease; Vascular disease; Human; Pathogenesis; Aneurysm; Cardiovascular disease; Aorta; Metalloproteinase; Aortic disease
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/01.CIR.96.7.2228

Despite a wealth of data detailing increased metalloproteinase (MMP)-9 expression and activity in abdominal aortic aneurysms (AAAs), no studies examine the relationship between aortic size and MMP-9 expression. Because elastolysis occurs early in AAA formation, we hypothesized that MMP-9 expression would vary with aortic diameter. The purpose of this study was to measure MMP-9 mRNA levels in AAAs of various diameters and define the relationship between AAA size and MMP-9 expression. MMP-9 mRNA levels were measured by competitive polymerase chain reaction (PCR) using gene-specific external standards with cDNA from AAAs (n= 19) and normal aortas (n=4). Levels were normalized to GAPDH mRNA, determined separately via competitive PCR, to control for efficiency of reverse transcription. AAA size was measured on CT scans obtained within 6 weeks of surgery. MMP-9/GAPDH mRNA transcript levels in AAAs were expressed as mean+/-SEM and analyzed by ANOVA with a Tukey adjustment. There was a fourfold elevation in MMP-9/GAPDH mRNA transcript levels in 5.0- to 6.9-cm AAAs (98.06+/-15.19) compared with small (3.0- to 4.9-cm) AAAs (20.87+/-5.15, P<.03), large (>7-cm) AAAs (27.16+/-14.56, P<.01), or normal aortas (3.57+/-1.13, P<.003). The results did not change when they were normalized to patient height, nor were there significant differences in risk factors, age, or sex in each AAA group. MMP-9 mRNA expression is significantly higher in moderate-diameter (5- to 6.9-cm) AAAs than either small (<4.0-cm) or large (>7.0-cm) AAAs. Increased MMP-9 expression may account for the propensity of AAAs >5 cm to continue to expand, in contrast to smaller aneurysms. Lower levels in AAAs >7 cm suggest that increases in other enzymes or in diameter-dependent mechanical stress on the aortic wall are responsible for their characteristic rapid expansion and high rupture rates.