| Title | A role for plasma transforming growth factor-beta and matrix metalloproteinases in aortic aneurysm surveillance in Marfan syndrome? | | Author(s) | Ahimastos AA, Aggarwal A, Savarirayan R, Dart AM, Kingwell BA | | Institution | Baker IDI Heart and Diabetes Research Institute, Melbourne, Australia. | | Source | Atherosclerosis 2009 Aug 8. | | Abstract | BACKGROUND: 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.
METHODS: 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.
RESULTS: Perindopril significantly reduced aortic root diameters relative to placebo in both end-systole and end-diastole (by 1.2-3mm/m(2), p<0.001). In addition, compared to placebo perindopril significantly reduced latent TGF-beta levels by 14.0+/-4.5ng/ml (p=0.01), active TGF-beta levels by 4+/-1ng/ml (p=0.02), MMP-2 levels by 22+/-6ng/ml (p<0.001), and MMP-3 levels by 5+/-1ng/ml (p<0.001). There were moderately strong correlations between the pre/post intervention change in aortic diameters and the change in both latent (r=0.49-0.76, p=0.001-0.04) and active TGF-beta (r=0.59-0.73, p=0.002-0.02), MMP-2 (r=0.63-0.75, p=0.001-0.007), and MMP-3 plasma levels (r=0.81-0.83, p<0.0001).
CONCLUSIONS: Plasma TGF-beta, MMP-2 and MMP-3 should be further explored in longitudinal trials as potential prognostic indicators of progression of aortic dilatation and response to therapy in MFS. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19717156 |
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