Megan E Bowen1, Xiaoqing Liu1, Peter M Sundwall1, Stavros G Drakos2, Dean Y Li2, Craig H Selzman1, Stephen H McKellar3. 1. Division of Cardiothoracic Surgery, Department of Surgery, University of Utah School of Medicine, Salt Lake City, Utah. 2. Department of Molecular Medicine, University of Utah School of Medicine, Salt Lake City, Utah. 3. Division of Cardiothoracic Surgery, Department of Surgery, University of Utah School of Medicine, Salt Lake City, Utah. Electronic address: stephen.mckellar@hsc.utah.edu.
Abstract
BACKGROUND: Right ventricular (RV) failure (RVF) is a vexing problem facing patients with various disease processes and carries a high mortality. RVF is a poorly understood phenomenon with limited treatment options. In mammalian fetal circulation, the right ventricle is the systemic ventricle. In neonates, however, the left ventricle assumes that role and gradually thickens compared with the right ventricle. This process, known as right ventricular involution (RVI), is poorly understood. We sought to define the time course and identify mechanisms involved in RVI. METHODS: Wild-type mice were bred and sacrificed on day of life (DOL) 1, 4, 8, 16, and 30 to evaluate left ventricular (LV) and RV wall thickness and apoptosis. A terminal deoxynucleotidyl transferase nick-end labeling assay and RNA sequencing were performed to measure changes during RVI. RESULTS: Morphometric analysis demonstrated the changes in RV and LV wall thickness occurring between DOL 1 and DOL 16 (RV:LV, 0.53:0.44; P = .03). In addition, apoptosis was most active early, with the highest percentage of apoptotic cells on DOL 1 (1.0%) and a significant decrease by DOL 30 (0.23%) (P = .02). Similarly, expression of the proapoptotic genes BCL2l11 and Pawr were increased at DOL 1, and the antiapoptotic genes Nol3 and Naip2 were significantly increased at DOL 30. CONCLUSIONS: RVI is a misnomer, but significant changes occur early (by DOL 16) in neonatal mouse hearts. Apoptosis plays a role in RVI, but whether manipulation of apoptotic pathways can prevent or reverse RVI is unknown and warrants further investigation.
BACKGROUND: Right ventricular (RV) failure (RVF) is a vexing problem facing patients with various disease processes and carries a high mortality. RVF is a poorly understood phenomenon with limited treatment options. In mammalian fetal circulation, the right ventricle is the systemic ventricle. In neonates, however, the left ventricle assumes that role and gradually thickens compared with the right ventricle. This process, known as right ventricular involution (RVI), is poorly understood. We sought to define the time course and identify mechanisms involved in RVI. METHODS: Wild-type mice were bred and sacrificed on day of life (DOL) 1, 4, 8, 16, and 30 to evaluate left ventricular (LV) and RV wall thickness and apoptosis. A terminal deoxynucleotidyl transferase nick-end labeling assay and RNA sequencing were performed to measure changes during RVI. RESULTS: Morphometric analysis demonstrated the changes in RV and LV wall thickness occurring between DOL 1 and DOL 16 (RV:LV, 0.53:0.44; P = .03). In addition, apoptosis was most active early, with the highest percentage of apoptotic cells on DOL 1 (1.0%) and a significant decrease by DOL 30 (0.23%) (P = .02). Similarly, expression of the proapoptotic genes BCL2l11 and Pawr were increased at DOL 1, and the antiapoptotic genes Nol3 and Naip2 were significantly increased at DOL 30. CONCLUSIONS: RVI is a misnomer, but significant changes occur early (by DOL 16) in neonatal mouse hearts. Apoptosis plays a role in RVI, but whether manipulation of apoptotic pathways can prevent or reverse RVI is unknown and warrants further investigation.
Authors: Vallerie V McLaughlin; Kenneth W Presberg; Ramona L Doyle; Steven H Abman; Douglas C McCrory; Terry Fortin; Gregory Ahearn Journal: Chest Date: 2004-07 Impact factor: 9.410
Authors: Stavros G Drakos; Lindsay Janicki; Benjamin D Horne; Abdallah G Kfoury; Bruce B Reid; Stephen Clayson; Kenneth Horton; Francois Haddad; Dean Y Li; Dale G Renlund; Patrick W Fisher Journal: Am J Cardiol Date: 2010-02-13 Impact factor: 2.778
Authors: Stephen H McKellar; Hadi Javan; Megan E Bowen; Xiaoquing Liu; Christin L Schaaf; Casey M Briggs; Huashan Zou; Arnold David Gomez; Osama M Abdullah; Ed W Hsu; Craig H Selzman Journal: J Surg Res Date: 2014-11-10 Impact factor: 2.192
Authors: Francesc X Sureda; Felix Junyent; Ester Verdaguer; Carme Auladell; Carme Pelegri; Jordi Vilaplana; Jaume Folch; Anna Maria Canudas; Carlos Beas Zarate; Merc Pallès; Antoni Camins Journal: Curr Pharm Des Date: 2011 Impact factor: 3.116
Authors: Brian D Lowes; Ronald Zolty; Simon F Shakar; Andreas Brieke; Norman Gray; Michael Reed; Mihail Calalb; Wayne Minobe; JoAnn Lindenfeld; Eugene E Wolfel; Mark Geraci; Michael R Bristow; Joseph Cleveland Journal: J Heart Lung Transplant Date: 2007-11 Impact factor: 10.247
Authors: Nikolaos A Diakos; Craig H Selzman; Frank B Sachse; Josef Stehlik; Abdallah G Kfoury; Omar Wever-Pinzon; Anna Catino; Rami Alharethi; Bruce B Reid; Dylan V Miller; Mohamed Salama; Alexey V Zaitsev; Junko Shibayama; Hui Li; James C Fang; Dean Y Li; Stavros G Drakos Journal: J Am Coll Cardiol Date: 2014-10-14 Impact factor: 24.094