title: The role of bioactive lipids in stem cell mobilization and homing: novel therapeutics for myocardial ischemia.
abstract: Despite significant advances in medical therapy and interventional strategies, the prognosis of millions of patients with acute myocardial infarction (AMI) and ischemic heart disease (IHD) remains poor. Currently, short of heart transplantation with all of its inherit limitations, there are no available treatment strategies that replace the infarcted myocardium. It is now well established that cardiomyocytes undergo continuous renewal, with contribution from bone marrow (BM)-derived stem/progenitor cells (SPCs). This phenomenon is upregulated during AMI by initiating multiple innate reparatory mechanisms through which BMSPCs are mobilized towards the ischemic myocardium and contribute to myocardial regeneration. While a role for the SDF-1/CXCR4 axis in retention of BMSPCs in bone marrow is undisputed, its exclusive role in their mobilization and homing to a highly proteolytic microenvironment, such as the ischemic/infarcted myocardium, is currently being challenged. Recent evidence suggests a pivotal role for bioactive lipids in the mobilization of BMSPCs at the early stages following AMI and their homing towards ischemic myocardium. This review highlights the recent advances in our understanding of the mechanisms of stem cell mobilization, provides newer evidence implicating bioactive lipids in BMSPC mobilization and differentiation, and discusses their potential as therapeutic agents in the treatment of IHD.
authors.affiliation: Gill Heart Institute and Division of Cardiovascular Medicine, University of Kentucky and Lexington VA Medical Center, Lexington, KY 40536-020, USA.
authors.forename: Yuri M
authors.initials: YM
authors.lastname: Klyachkin
authors.affiliation: Gill Heart Institute and Division of Cardiovascular Medicine, University of Kentucky and Lexington VA Medical Center, Lexington, KY 40536-020, USA.
authors.forename: Anush V
authors.initials: AV
authors.lastname: Karapetyan
authors.affiliation: Stem Cell Biology Institute, James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA ; Department of Physiology, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Mariusz Z
authors.initials: MZ
authors.lastname: Ratajczak
authors.affiliation: Gill Heart Institute and Division of Cardiovascular Medicine, University of Kentucky and Lexington VA Medical Center, Lexington, KY 40536-020, USA.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Abdel-Latif
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects; D002630:Chemotactic Factors / Q000494:pharmacology; D019650:Hematopoietic Stem Cell Mobilization; D006801:Humans; D008055:Lipids / Q000494:pharmacology*; D017202:Myocardial Ischemia / Q000628:therapy*; D013107:Sphingolipids / Q000378:metabolism
chemical_list: D002630:Chemotactic Factors; D008055:Lipids; D013107:Sphingolipids