© 2008 European Society of Cardiology
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
a Department of Cardiothoracic Surgery, Ullevål University Hospital Oslo, Norway
b Faculty of Medicine, University of Oslo Oslo, Norway
c Department of Cardiology, Ullevål University Hospital Oslo, Norway
d Institute for Experimental Medical Research, Ullevål University Hospital Oslo, Norway
e Center for Heart Failure Research, University of Oslo Oslo, Norway
f Department of Cardiac Surgery, The Royal Brompton Hospital London, UK
* Corresponding author. Department of Cardiothoracic Surgery, Ullevål University Hospital, Oslo, Norway. Tel./fax: +47 23015268. E-mail address: thto{at}uus.no (T. Tønnessen).
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Abstract |
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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) 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-β3, 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-β3 was only slightly reduced at six months postoperatively.
Conclusion: The observed alteration in circulating levels of members of the TGF-β superfamily and MMPs might play a role in the reverse remodelling process following AVR for AS.
Key Words: Myocardial remodelling • Aortic valve replacement • TGF-β • Growth factors • Activin A • GDF-15 • MMP
Received August 17, 2008; Accepted September 25, 2008