科研之友
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摘要
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 1.2-3 mm/m(2), p < 0.001). In addition, compared to placebo perindopril significantly reduced latent TGF-beta levels by 14.0 +/- 4.5 ng/ml (p = 0.01), active TGF-beta levels by 4 +/- 1 ng/ml (p = 0.02), MMP-2 levels by 22 +/- 6 ng/ml (p < 0.001), and MMP-3 levels by 5 +/- 1 ng/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.
- 出版日期2010-3
