TY - JOUR
T1 - Expression of Extracellular Matrix Genes During Myocardial Recovery From Heart Failure After Left Ventricular Assist Device Support
AU - Felkin, Leanne E.
AU - Lara-Pezzi, Enrique
AU - George, Robert
AU - Yacoub, Magdi H.
AU - Birks, Emma J.
AU - Barton, Paul J.R.
PY - 2009/2
Y1 - 2009/2
N2 - Background: Abnormalities in the extracellular matrix (ECM) can occur in heart failure. In this study we analyzed ECM gene expression in patients with advanced dilated cardiomyopathy who did and did not develop sustained myocardial recovery after left ventricular asst device (LVAD) unloading combined with pharmacologic therapy. Methods: Myocardial gene expression of collagens (COL1A1 and COL3A1), fibronectin (FN), matrix metalloproteinases (MMPs 1 to 14), tissue inhibitors of metalloproteinases (TIMPs 1 to 4), connective tissue growth factor (CTGF), transforming growth factor-beta1 (TGF-β1) and THY1 was measured by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) at LVAD implantation and again at explantation (recovery, n = 11) or transplantation (non-recovery, n = 5). Results: The non-recovery group had higher levels of pro-fibrotic markers (COL1A1, TGF-β1 and THY1) at implantation compared with the recovery group (1.82 ± 0.74-, 1.81 ± 0.69- and 3.01 ± 1.70-fold, respectively; p ≤ 0.05). Both recovery and non-recovery groups showed no significant difference in gene expression after treatment, but levels of pro-fibrotic genes (COL1A1, COL3A1, FN and THY1) correlated negatively with post-explant ejection fraction in the recovery group. Of all genes analyzed only TIMP4 showed a significant change, with expression reduced during recovery (0.55 ± 0.25-fold at explant vs implant, p = 0.001). All other genes showed complex patterns between individuals with both increased and decreased expression of pro-fibrotic markers, MMPs and TIMPs in recovery patients. Conclusions: Patients who did not recover had higher myocardial expression of pro-fibrotic genes at LVAD implantation, and in recovered patients higher levels at explant were negatively associated with subsequent ejection fraction. However, individual patients showed complex expression patterns and a decrease in pro-fibrotic markers was not required for recovery.
AB - Background: Abnormalities in the extracellular matrix (ECM) can occur in heart failure. In this study we analyzed ECM gene expression in patients with advanced dilated cardiomyopathy who did and did not develop sustained myocardial recovery after left ventricular asst device (LVAD) unloading combined with pharmacologic therapy. Methods: Myocardial gene expression of collagens (COL1A1 and COL3A1), fibronectin (FN), matrix metalloproteinases (MMPs 1 to 14), tissue inhibitors of metalloproteinases (TIMPs 1 to 4), connective tissue growth factor (CTGF), transforming growth factor-beta1 (TGF-β1) and THY1 was measured by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) at LVAD implantation and again at explantation (recovery, n = 11) or transplantation (non-recovery, n = 5). Results: The non-recovery group had higher levels of pro-fibrotic markers (COL1A1, TGF-β1 and THY1) at implantation compared with the recovery group (1.82 ± 0.74-, 1.81 ± 0.69- and 3.01 ± 1.70-fold, respectively; p ≤ 0.05). Both recovery and non-recovery groups showed no significant difference in gene expression after treatment, but levels of pro-fibrotic genes (COL1A1, COL3A1, FN and THY1) correlated negatively with post-explant ejection fraction in the recovery group. Of all genes analyzed only TIMP4 showed a significant change, with expression reduced during recovery (0.55 ± 0.25-fold at explant vs implant, p = 0.001). All other genes showed complex patterns between individuals with both increased and decreased expression of pro-fibrotic markers, MMPs and TIMPs in recovery patients. Conclusions: Patients who did not recover had higher myocardial expression of pro-fibrotic genes at LVAD implantation, and in recovered patients higher levels at explant were negatively associated with subsequent ejection fraction. However, individual patients showed complex expression patterns and a decrease in pro-fibrotic markers was not required for recovery.
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U2 - 10.1016/j.healun.2008.11.910
DO - 10.1016/j.healun.2008.11.910
M3 - Article
C2 - 19201335
AN - SCOPUS:59349095082
SN - 1053-2498
VL - 28
SP - 117
EP - 122
JO - Journal of Heart and Lung Transplantation
JF - Journal of Heart and Lung Transplantation
IS - 2
ER -