Plasma levels of transforming growth factor-beta1 reflect left ventricular remodeling in aortic stenosis.

<h4>Background</h4>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 i...

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Autores principales: Ana V Villar, Manuel Cobo, Miguel Llano, Cecilia Montalvo, Francisco González-Vílchez, Rafael Martín-Durán, María A Hurlé, J Francisco Nistal
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Publicado: Public Library of Science (PLoS) 2009
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spelling oai:doaj.org-article:b69c4889c40646068e960877e82eb0652021-11-25T06:27:05ZPlasma levels of transforming growth factor-beta1 reflect left ventricular remodeling in aortic stenosis.1932-620310.1371/journal.pone.0008476https://doaj.org/article/b69c4889c40646068e960877e82eb0652009-12-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20041033/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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.<h4>Conclusions/significance</h4>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.Ana V VillarManuel CoboMiguel LlanoCecilia MontalvoFrancisco González-VílchezRafael Martín-DuránMaría A HurléJ Francisco NistalPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 4, Iss 12, p e8476 (2009)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Ana V Villar
Manuel Cobo
Miguel Llano
Cecilia Montalvo
Francisco González-Vílchez
Rafael Martín-Durán
María A Hurlé
J Francisco Nistal
Plasma levels of transforming growth factor-beta1 reflect left ventricular remodeling in aortic stenosis.
description <h4>Background</h4>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.<h4>Methodology/principal findings</h4>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.<h4>Conclusions/significance</h4>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.
format article
author Ana V Villar
Manuel Cobo
Miguel Llano
Cecilia Montalvo
Francisco González-Vílchez
Rafael Martín-Durán
María A Hurlé
J Francisco Nistal
author_facet Ana V Villar
Manuel Cobo
Miguel Llano
Cecilia Montalvo
Francisco González-Vílchez
Rafael Martín-Durán
María A Hurlé
J Francisco Nistal
author_sort Ana V Villar
title Plasma levels of transforming growth factor-beta1 reflect left ventricular remodeling in aortic stenosis.
title_short Plasma levels of transforming growth factor-beta1 reflect left ventricular remodeling in aortic stenosis.
title_full Plasma levels of transforming growth factor-beta1 reflect left ventricular remodeling in aortic stenosis.
title_fullStr Plasma levels of transforming growth factor-beta1 reflect left ventricular remodeling in aortic stenosis.
title_full_unstemmed Plasma levels of transforming growth factor-beta1 reflect left ventricular remodeling in aortic stenosis.
title_sort plasma levels of transforming growth factor-beta1 reflect left ventricular remodeling in aortic stenosis.
publisher Public Library of Science (PLoS)
publishDate 2009
url https://doaj.org/article/b69c4889c40646068e960877e82eb065
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