A role for plasma transforming growth factor-β and matrix metalloproteinases in aortic aneurysm surveillance in Marfan syndrome?

• Published in: Atherosclerosis 2010-03, Vol.209 (1), p.211-214
• Main Authors: AHIMASTOS, Anna A, AGGARWAL, Anuradha, SAVARIRAYAN, Ravi, DART, Anthony M, KINGWELLA, Bronwyn A
• Format: Article
• Language: English
• Subjects: Adult; Angiotensin-Converting Enzyme Inhibitors - therapeutic use; Aortic Aneurysm - blood; Aortic Aneurysm - etiology; Aortic Aneurysm - prevention & control; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Biomarkers - blood; Blood and lymphatic vessels; Cardiology. Vascular system; Diseases of the aorta; Female; Humans; Male; Marfan Syndrome - blood; Marfan Syndrome - complications; Marfan Syndrome - drug therapy; Matrix Metalloproteinase 2 - blood; Matrix Metalloproteinase 3 - blood; Matrix Metalloproteinase Inhibitors; Medical sciences; Perindopril - therapeutic use; Randomized Controlled Trials as Topic; Transforming Growth Factor beta - antagonists & inhibitors; Transforming Growth Factor beta - blood
• ISSN: 0021-9150; 1879-1484
• DOI: 10.1016/j.atherosclerosis.2009.08.003

We have previously shown that the angiotensin-converting enzyme (ACE) inhibitor perindopril reduced aortic diameter by 3-7mm in Marfan syndrome (MFS) patients. Excessive signalling by the transforming growth factor-beta (TGF-beta) has been implicated in the development of aortic dilatation. We hypothesised that reduction in aortic diameter would correlate with reduction in plasma TGF-beta and matrix metalloproteinase (MMP) levels. 17 MFS patients (aged 33+/-5 (mean+/-SD)) on standard beta-blocker therapy were randomised to also receive perindopril (n=10) or placebo (n=7) for 24 weeks in a double blind study. Aortic root diameters were assessed at four sites via transthoracic echocardiography. Venous blood samples were analysed for latent and active TGF-beta, MMP-2 and MMP-3 levels. Perindopril significantly reduced aortic root diameters relative to placebo in both end-systole and end-diastole (by 1.2-3mm/m(2), p