Alterations in circulating activin A, GDF-15, TGF-β3 and MMP-2,-3, and-9 during one year of left ventricular reverse remodelling in patients operated for severe aortic stenosis

Background: Patients with aortic stenosis (AS) develop left ventricular remodelling with cardiomyocyte hypertrophy and increased fibrosis. Following aortic valve replacement (AVR) reverse remodelling usually takes place. Aims: To examine circulating levels of members of the transforming growth factor (TGF) beta superfamily and matrix metalloproteinases (MMP), known to have important effects on hypertrophy and extracellular matrix, in patients operated for AS. Methods: Circulating levels of activin A, GDF-15, TGF-beta 3, MMP-2, -3, and -9 were measured in twenty-two patients undergoing AVR preoperatively, and 2 days, six months and 12 months postoperatively. Echocardiography and a six minute walking test evaluated reverse remodelling and physical performance. Results: Activin A increased at six (1081.00 +/- 98.05 pg/ml, p < 0.05) and twelve months (1263.09 +/- 141.43 pg/ml, p < 0.05) compared to the preoperative value (855.00 +/- 76.30 pg/ml) and correlated negatively to physical performance. The preoperative value was also increased compared to controls (639.54 +/- 63.05 pg/ml, p < 0.05). GDF-15, MMP-3 and -9 were all increased at two days postoperatively (p < 0.05). MMP-3 Correlated with left ventricular end diastolic dimension (p < 0.05). MMP-2 did not change during the study period. TGF-beta 3 was only slightly reduced at six months postoperatively. Conclusion: The observed alteration in circulating levels of members of the TGF-beta superfamily and MMPs might play a role in the reverse remodelling process following AVR for AS. (C) 2008 Published by Elsevier B.V. on behalf of European Society of Cardiology.