Plasma levels of transforming growth factor-beta1 reflect left ventricular remodeling in aortic stenosis
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AuthorVillar Ramos, Ana Victoria; Cobo Belaustegui, Manuel; Llano Cardenal, Miguel; Montalvo Silva, Cecilia de; González-Vílchez, Francisco; Martín Durán, Rafael; Hurlé González, María Amor; Nistal Herrera, Juan Francisco
Background: TGF-b1 is involved in cardiac remodeling through an auto/paracrine mechanism. The contribution of TGF-b1
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-b1
relates with myocardial remodeling, reflected by LV transcriptional adaptations of genes linked to myocardial hypertrophy
and fibrosis, and by heart morphology and function.
Methodology/Principal Findings: 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-b1
was determined by ELISA. Under pressure overload, TGF-b1 plasma levels were significantly increased both in AS patients
and TAC mice. In AS patients, plasma TGF-b1 correlated directly with aortic transvalvular gradients and LV mass surrogate
variables, both preoperatively and 1 year after surgery. Plasma TGF-b1 correlated positively with the myocardial expression
of genes encoding extracellular matrix (collagens I and III, fibronectin) and sarcomeric (myosin light chain-2, b-myosin heavy
chain) remodelling targets of TGF-b1, in TAC mice and in AS patients.
Conclusions/Significance: A circulating TGF-b1-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-b1 as a marker reflecting preoperative myocardial remodeling status in AS patients deserves further
analysis in larger patient cohorts.
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