title: Mechanisms Contributing to the Progression of Ischemic and Nonischemic Dilated Cardiomyopathy: Possible Modulating Effects of Paracrine Activities of Stem Cells.
abstract: Over the past 1.5 decades, numerous stem cell trials have been performed in patients with cardiovascular disease. Although encouraging outcome signals have been reported, these have been small, leading to uncertainty as to whether they will translate into significantly improved outcomes. A reassessment of the rationale for the use of stem cells in cardiovascular disease is therefore timely. Such a rationale should include analyses of why previous trials have not produced significant benefit and address whether mechanisms contributing to disease progression might benefit from known activities of stem cells. The present paper provides such a reassessment, focusing on patients with left ventricular systolic dysfunction, either nonischemic or ischemic. We conclude that many mechanisms contributing to progressive left ventricular dysfunction are matched by stem cell activities that could attenuate the myocardial effect of such mechanisms. This suggests that stem cell strategies may improve patient outcomes and justifies further testing.
authors.affiliation: Cardiology Division, Emory University, Atlanta, Georgia.
authors.forename: Anita A
authors.initials: AA
authors.lastname: Kelkar
authors.affiliation: Stony Brook University, Stony Brook, New York. Electronic address: javed.butler@stonybrookmedicine.edu.
authors.forename: Javed
authors.initials: J
authors.lastname: Butler
authors.affiliation: Cardiology Division, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Erik B
authors.initials: EB
authors.lastname: Schelbert
authors.affiliation: Center for Cardiovascular Innovation, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Greene
authors.affiliation: Cardiology Division, Emory University, Atlanta, Georgia.
authors.forename: Arshed A
authors.initials: AA
authors.lastname: Quyyumi
authors.affiliation: Center for Cardiovascular Innovation, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Robert O
authors.initials: RO
authors.lastname: Bonow
authors.affiliation: Stony Brook University, Stony Brook, New York.
authors.forename: Ira
authors.initials: I
authors.lastname: Cohen
authors.affiliation: Center for Cardiovascular Innovation, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Mihai
authors.initials: M
authors.lastname: Gheorghiade
authors.affiliation: MedStar Heart and Vascular Institute, MedStar Washington Hospital Center, Washington, DC.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Lipinski
authors.affiliation: MedStar Heart and Vascular Institute, MedStar Washington Hospital Center, Washington, DC.
authors.forename: Wei
authors.initials: W
authors.lastname: Sun
authors.affiliation: MedStar Heart and Vascular Institute, MedStar Washington Hospital Center, Washington, DC.
authors.forename: Dror
authors.initials: D
authors.lastname: Luger
authors.affiliation: MedStar Heart and Vascular Institute, MedStar Washington Hospital Center, Washington, DC.
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Epstein
mesh_terms: D002311:Cardiomyopathy, Dilated / Q000209:etiology / Q000503:physiopathology / Q000628:therapy; D018450:Disease Progression; D006801:Humans; D017202:Myocardial Ischemia / Q000150:complications; D017063:Outcome Assessment, Health Care; D033581:Stem Cell Transplantation / Q000379:methods / Q000706:statistics & numerical data; D018487:Ventricular Dysfunction, Left / Q000209:etiology / Q000503:physiopathology / Q000628:therapy
keywords: cardiac; cell- and tissue-based therapy; extracellular matrix; heart failure; inflammation; myocardium; myocytes; paracrine mechanisms