Enhanced bioactive tgf-levels in the myocardium suggests early pathological transition in asymptomatic severe mitral regurgitation

L Malebranche, S Khan, M Saltzberg, M Banbury… - Journal of the American …, 2014 - jacc.org
L Malebranche, S Khan, M Saltzberg, M Banbury, A DiSabatino, A Squire, T Tsuda
Journal of the American College of Cardiology, 2014jacc.org
Background The optimal timing of surgery for asymptomatic severe mitral regurgitation (MR)
remains debatable. Excessive TGF-b activation is known to lead to pathological remodeling
of the ventricular myocardium. Methods Myocardial tissue and blood samples were collected
from patients with severe MR undergoing mitral valve surgery (MVR: N= 10), end stage heart
failure undergoing Left Ventricular Assist Device implantation (LVAD: N= 7), and non-failing
donor hearts (NF: N= 7). We examined plasma and myocardial TGF-b levels by bioassay …
Background
The optimal timing of surgery for asymptomatic severe mitral regurgitation (MR) remains debatable. Excessive TGF-b activation is known to lead to pathological remodeling of the ventricular myocardium.
Methods
Myocardial tissue and blood samples were collected from patients with severe MR undergoing mitral valve surgery (MVR: N= 10), end stage heart failure undergoing Left Ventricular Assist Device implantation (LVAD: N= 7), and non-failing donor hearts (NF: N= 7). We examined plasma and myocardial TGF-b levels by bioassay, mRNA levels of TGF-b1, collagen type I, type III, MMP-2, and TGF-b downstream signals (Smad2 and ERK1/2) by immunoblots. Data are shown as mean±SEM.
Results
See Table 1. Plasma TGF-b levels were significantly higher in LVAD than in MVR. Myocardial TGF-b was significantly higher in MVR and LVAD than in NF, but also surprisingly higher in MVR than in LVAD. Activation of TGF-b downstream signals, Smad2 and ERK1/2, were significantly increased in both MVR and LVAD compared with NF. Markers of myocardial fibrosis, Col I and MMP2 mRNA were significantly up-regulated in LVAD compared with MVR.
Conclusion
Asymptomatic MVR with preserved ejection fraction (EF) showed significantly higher myocardial TGF-β activity levels than LVAD, indicating that MVR are already on the process of pathological remodeling despite a normal EF.
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