β-Adrenergic Regulation of Cardiac Progenitor Cell Death Versus Survival and Proliferation
Mohsin Khan,Sadia Mohsin,Daniele Avitabile,Sailay Siddiqi,Jonathan Nguyen,Kathleen Wallach,Pearl Quijada,Michael McGregor,Natalie Gude,Roberto Alvarez,Douglas G. Tilley,Walter J. Koch,Mark A. Sussman +12 more
TLDR
Investigation of the relationship between adrenergic activity and regulation of CPC function found acquisition of &bgr;1-AR on commitment to the myocyte lineage results in loss of CPCs and early myocyte precursors.Abstract:
Rationale:Short-term β-adrenergic stimulation promotes contractility in response to stress but is ultimately detrimental in the failing heart because of accrual of cardiomyocyte death. Endogenous cardiac progenitor cell (CPC) activation may partially offset cardiomyocyte losses, but consequences of long-term β-adrenergic drive on CPC survival and proliferation are unknown. Objective:We sought to determine the relationship between β-adrenergic activity and regulation of CPC function. Methods and Results:Mouse and human CPCs express only β2 adrenergic receptor (β2-AR) in conjunction with stem cell marker c-kit. Activation of β2-AR signaling promotes proliferation associated with increased AKT, extracellular signal-regulated kinase 1/2, and endothelial NO synthase phosphorylation, upregulation of cyclin D1, and decreased levels of G protein–coupled receptor kinase 2. Conversely, silencing of β2-AR expression or treatment with β2-antagonist ICI 118, 551 impairs CPC proliferation and survival. β1-AR expression...read more
Citations
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Journal ArticleDOI
BNIP3L/NIX and FUNDC1-mediated mitophagy is required for mitochondrial network remodeling during cardiac progenitor cell differentiation
Mark A Lampert,Amabel M. Orogo,Rita H. Najor,Babette C. Hammerling,Leonardo J. Leon,Bingyan J. Wang,Taeyong Kim,Mark A. Sussman,Åsa B. Gustafsson +8 more
TL;DR: The importance of BNIP3L- and FUNDC1-mediated mitophagy as a critical regulator of mitochondrial network formation during differentiation, as well as the consequences of accumulating mtDNA mutations, is demonstrated.
Journal ArticleDOI
Epigenetic Regulation of Phosphodiesterases 2A and 3A Underlies Compromised β-Adrenergic Signaling in an iPSC Model of Dilated Cardiomyopathy.
Haodi Wu,Jae Cheol Lee,Ludovic G. Vincent,Qingtong Wang,Mingxia Gu,Feng Lan,Jared M. Churko,Karim Sallam,Elena Matsa,Arun Sharma,Joseph D. Gold,Adam J. Engler,Yang Kevin Xiang,Donald M. Bers,Joseph C. Wu +14 more
TL;DR: In this article, the β-adrenergic pathway was blunted in dilated cardiomyopathy (DCM) patients with a mutation in TNNT2, a sarcomeric protein.
Journal ArticleDOI
Fibronectin Is Essential for Reparative Cardiac Progenitor Cell Response After Myocardial Infarction
Mathias H. Konstandin,Haruhiro Toko,Grady Gastelum,Pearl Quijada,Andrea De La Torre,Mercedes Quintana,Brett Collins,Shabana Din,Daniele Avitabile,Mirko Völkers,Natalie Gude,Reinhard Fässler,Mark A. Sussman +12 more
TL;DR: Fn is essential for endogenous CPC expansion and repair required for stabilization of cardiac function after MI, and is shown to correlates with the expression of Fn during cardiac development and after MI.
Journal ArticleDOI
Transient Introduction of miR-294 in the Heart Promotes Cardiomyocyte Cell Cycle Reentry After Injury
Austin Borden,Justin Kurian,Emily Nickoloff,Yijun Yang,Constantine D Troupes,Jessica Ibetti,Anna Maria Lucchese,Erhe Gao,Sadia Mohsin,Walter J. Koch,Steven R. Houser,Raj Kishore,Mohsin Khan +12 more
TL;DR: Ectopic transient expression of miR-294 recapitulates developmental signaling and phenotype in cardiomyocytes promoting cell cycle reentry that leads to augmented cardiac function in mice after myocardial infarction.
Journal ArticleDOI
Effects of physiologic mechanical stimulation on embryonic chick cardiomyocytes using a microfluidic cardiac cell culture model.
Mai-Dung Nguyen,Joseph P. Tinney,Fei Ye,Ahmed Elnakib,Fangping Yuan,Ayman El-Baz,Palaniappan Sethu,Bradley B. Keller,Guruprasad A. Giridharan +8 more
TL;DR: Early mechanical stimulation of embryonic cardiac tissue is necessary for tissue proliferation and for protein synthesis of the calcium handling constituents required for tissue contractility, and physiologic mechanical conditioning may be essential for generating functional cardiac patches for replacement of injured cardiac tissue.
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