Plasma Levels of Transforming Growth Factor-β1 Reflect Left Ventricular Remodeling in Aortic Stenosis

• Published in: PloS one Vol. 4; no. 12; p. e8476
• Main Authors: Villar, Ana V., Cobo, Manuel, Llano, Miguel, Montalvo, Cecilia, González-Vílchez, Francisco, Martín-Durán, Rafael, Hurlé, María A., Nistal, J. Francisco
• Format: Journal Article
• Language: English
• Published: San Francisco Public Library of Science 30.12.2009
• Subjects: Adaptation; Aorta; Aortic arch; Aortic stenosis; Apoptosis; Calcification; Cardiomyocytes; Cardiovascular disease; Cardiovascular Disorders; Cardiovascular Disorders/Heart Failure; Chains; Collagen; Cytokines; Diuretics; Enzyme-linked immunosorbent assay; Eutrophication; Extracellular matrix; Fibroblasts; Fibronectin; Fibrosis; Gender differences; Gene expression; Genes; Growth factors; Heart; Heart diseases; Heart failure; Hypertension; Hypertrophy; Kinases; Marfan syndrome; Men; Mice; Myosin; Paracrine signalling; Patients; Physiology/Cardiovascular Physiology and Circulation; Plasma levels; Plasmas (physics); Pressure; Rodents; Stenosis; Surgery; Transcription; Transforming growth factor; Transforming growth factor-b1; Ventricle; Womens health
• DOI: 10.1371/journal.pone.0008476
• ISSN: 1932-6203

Background TGF-β1 is involved in cardiac remodeling through an auto/paracrine mechanism. The contribution of TGF-β1 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-β1 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-β1 was determined by ELISA. Under pressure overload, TGF-β1 plasma levels were significantly increased both in AS patients and TAC mice. In AS patients, plasma TGF-β1 correlated directly with aortic transvalvular gradients and LV mass surrogate variables, both preoperatively and 1 year after surgery. Plasma TGF-β1 correlated positively with the myocardial expression of genes encoding extracellular matrix (collagens I and III, fibronectin) and sarcomeric (myosin light chain-2, β-myosin heavy chain) remodelling targets of TGF-β1, in TAC mice and in AS patients. Conclusions/Significance A circulating TGF-β1-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-β1 as a marker reflecting preoperative myocardial remodeling status in AS patients deserves further analysis in larger patient cohorts.