Alterations in circulating activin A, GDF-15, TGF-beta3 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.


OBJECTIVE
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-beta3, 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-beta3 was only slightly reduced at six months postoperatively.


CONCLUSIONS
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.
Bjørnstad
Johannes L
JL
Department of Cardiothoracic Surgery, Ullevål University Hospital, Oslo, Norway.
Neverdal
Nils O
NO
Vengen
Oystein A
OA
Knudsen
Cathrine Wold
CW
Husebye
Trygve
T
Pepper
John
J
Lie
Mons
M
Christensen
Geir
G
Tønnessen
Theis
T
D028341:Activins / Q000097:blood*; D000368:Aged; D001024:Aortic Valve Stenosis / Q000097:blood / Q000503:physiopathology* / Q000601:surgery; D015415:Biomarkers / Q000097:blood; D005260:Female; D005355:Fibrosis / Q000503:physiopathology; D055436:Growth Differentiation Factor 15 / Q000097:blood*; D006350:Heart Valve Prosthesis; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000097:blood / Q000000981:diagnostic imaging / Q000503:physiopathology*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood*; D019278:Matrix Metalloproteinase 3 / Q000097:blood*; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D011446:Prospective Studies; D012307:Risk Factors; D053782:Transforming Growth Factor beta3 / Q000097:blood*; D014463:Ultrasonography
D015415:Biomarkers; D055436:Growth Differentiation Factor 15; D053782:Transforming Growth Factor beta3; C422405:activin A; D028341:Activins; D019278:Matrix Metalloproteinase 3; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9