title: Adolescent feline heart contains a population of small, proliferative ventricular myocytes with immature physiological properties.
abstract: Recent studies suggest that rather than being terminally differentiated, the adult heart is a self-renewing organ with the capacity to generate new myocytes from cardiac stem/progenitor cells (CS/PCs). This study examined the hypotheses that new myocytes are generated during adolescent growth, to increase myocyte number, and these newly formed myocytes are initially small, mononucleated, proliferation competent, and have immature properties. Ventricular myocytes (VMs) and cKit(+) (stem cell receptor) CS/PCs were isolated from 11- and 22-week feline hearts. Bromodeoxyuridine incorporation (in vivo) and p16(INK4a) immunostaining were measured to assess myocyte cell cycle activity and senescence, respectively. Telomerase activity, contractions, Ca(2+) transients, and electrophysiology were compared in small mononucleated (SMMs) and large binucleated (LBMs) myocytes. Heart mass increased by 101% during adolescent growth, but left ventricular myocyte volume only increased by 77%. Most VMs were binucleated (87% versus 12% mononucleated) and larger than mononucleated myocytes. A greater percentage of SMMs was bromodeoxyuridine positive (SMMs versus LBMs: 3.1% versus 0.8%; P<0.05), and p16(INK4a) negative and small myocytes had greater telomerase activity than large myocytes. Contractions and Ca(2+) transients were prolonged in SMMs versus LBMs and Ca(2+) release was disorganized in SMMs with reduced transient outward current and T-tubule density. The T-type Ca(2+) current, usually seen in fetal/neonatal VMs, was found exclusively in SMMs and in myocytes derived from CS/PC. Myocyte number increases during adolescent cardiac growth. These new myocytes are initially small and functionally immature, with patterns of ion channel expression normally found in the fetal/neonatal period.
authors.affiliation: Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, PA 19140, USA.
authors.forename: Xiongwen
authors.initials: X
authors.lastname: Chen
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Wilson
authors.forename: Hajime
authors.initials: H
authors.lastname: Kubo
authors.forename: Remus M
authors.initials: RM
authors.lastname: Berretta
authors.forename: David M
authors.initials: DM
authors.lastname: Harris
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Zhang
authors.forename: Naser
authors.initials: N
authors.lastname: Jaleel
authors.forename: Scott M
authors.initials: SM
authors.lastname: MacDonnell
authors.forename: Claudia
authors.initials: C
authors.lastname: Bearzi
authors.forename: Jochen
authors.initials: J
authors.lastname: Tillmanns
authors.forename: Irina
authors.initials: I
authors.lastname: Trofimova
authors.forename: Toru
authors.initials: T
authors.lastname: Hosoda
authors.forename: Federico
authors.initials: F
authors.lastname: Mosna
authors.forename: Leanne
authors.initials: L
authors.lastname: Cribbs
authors.forename: Annarosa
authors.initials: A
authors.lastname: Leri
authors.forename: Jan
authors.initials: J
authors.lastname: Kajstura
authors.forename: Piero
authors.initials: P
authors.lastname: Anversa
authors.forename: Steven R
authors.initials: SR
authors.lastname: Houser
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D020013:Calcium Signaling / Q000502:physiology; D002415:Cats; D049108:Cell Enlargement; D049109:Cell Proliferation; D002478:Cells, Cultured; D006321:Heart / Q000033:anatomy & histology / Q000254:growth & development*; D006352:Heart Ventricles / Q000166:cytology / Q000254:growth & development; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000502:physiology*