Plasma levels of transforming growth factor-beta1 reflect left ventricular remodeling in aortic stenosis.
BACKGROUND
TGF-beta1 is involved in cardiac remodeling through an auto/paracrine mechanism. The contribution of TGF-beta1 from plasmatic source to pressure overload myocardial remodeling has not been analyzed. We investigated, in patients with valvular aortic stenosis (AS), and in mice subjected to transverse aortic arch constriction (TAC), whether plasma TGF-beta1 relates with myocardial remodeling, reflected by LV transcriptional adaptations of genes linked to myocardial hypertrophy and fibrosis, and by heart morphology and function.


RESULTS
The subjects of the study were: 39 patients operated of AS; 27 healthy volunteers; 12 mice subjected to TAC; and 6 mice sham-operated. Myocardial samples were subjected to quantitative PCR. Plasma TGF-beta1 was determined by ELISA. Under pressure overload, TGF-beta1 plasma levels were significantly increased both in AS patients and TAC mice. In AS patients, plasma TGF-beta1 correlated directly with aortic transvalvular gradients and LV mass surrogate variables, both preoperatively and 1 year after surgery. Plasma TGF-beta1 correlated positively with the myocardial expression of genes encoding extracellular matrix (collagens I and III, fibronectin) and sarcomeric (myosin light chain-2, beta-myosin heavy chain) remodelling targets of TGF-beta1, in TAC mice and in AS patients.


CONCLUSIONS
A circulating TGF-beta1-mediated mechanism is involved, in both mice and humans, in the excessive deposition of ECM elements and hypertrophic growth of cardiomyocytes under pressure overload. The possible value of plasma TGF-beta1 as a marker reflecting preoperative myocardial remodeling status in AS patients deserves further analysis in larger patient cohorts.
Villar
Ana V
AV
División de Farmacología, Facultad de Medicina, Universidad de Cantabria, Instituto de Formación e Investigación Marqués de Valdecilla, Santander, Cantabria, Spain.
Cobo
Manuel
M
Llano
Miguel
M
Montalvo
Cecilia
C
González-Vílchez
Francisco
F
Martín-Durán
Rafael
R
Hurlé
María A
MA
Nistal
J Francisco
JF
D000368:Aged; D000818:Animals; D001024:Aortic Valve Stenosis / Q000097:blood* / Q000000981:diagnostic imaging / Q000503:physiopathology*; D006332:Cardiomegaly / Q000097:blood / Q000150:complications / Q000000981:diagnostic imaging; D016022:Case-Control Studies; D003710:Demography; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006350:Heart Valve Prosthesis; D006352:Heart Ventricles / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008297:Male; D051379:Mice; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009929:Organ Size; D011182:Postoperative Care; D011300:Preoperative Care; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012518:Sarcomeres / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D053773:Transforming Growth Factor beta1 / Q000097:blood*; D014463:Ultrasonography; D020257:Ventricular Remodeling / Q000235:genetics / Q000502:physiology*
D016326:Extracellular Matrix Proteins; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1