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 assist 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-beta1) 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-beta1 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 <or= 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.
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 assist 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-beta1) 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-beta1 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 <or= 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.
Authors: Stavros G Drakos; Abdallah G Kfoury; Josef Stehlik; Craig H Selzman; Bruce B Reid; John V Terrovitis; John N Nanas; Dean Y Li Journal: Circulation Date: 2012-07-10 Impact factor: 29.690
Authors: Leanne Elizabeth Felkin; Enrique A Lara-Pezzi; Jennifer L Hall; Emma J Birks; Paul J R Barton Journal: J Cardiovasc Transl Res Date: 2011-03-22 Impact factor: 4.132
Authors: Navin K Kapur; Szuhuei Wilson; Adil A Yunis; Xiaoying Qiao; Emily Mackey; Vikram Paruchuri; Corey Baker; Mark J Aronovitz; S Ananth Karumanchi; Michelle Letarte; David A Kass; Michael E Mendelsohn; Richard H Karas Journal: Circulation Date: 2012-05-16 Impact factor: 29.690
Authors: Deepak K Gupta; Hicham Skali; Jose Rivero; Patricia Campbell; Leslie Griffin; Colleen Smith; Courtney Foster; Brian Claggett; Robert J Glynn; Gregory Couper; Michael M Givertz; Mandeep R Mehra; Marcelo Di Carli; Scott D Solomon; Marc A Pfeffer Journal: J Heart Lung Transplant Date: 2014-01-27 Impact factor: 10.247
Authors: Zaid I Almarzooq; Anubodh S Varshney; Muthiah Vaduganathan; Manan Pareek; Garrick C Stewart; Jerry D Estep; Mandeep R Mehra Journal: JACC Cardiovasc Imaging Date: 2019-09-18