title: Intravenous and intramyocardial injection of apoptotic white blood cell suspensions prevents ventricular remodelling by increasing elastin expression in cardiac scar tissue after myocardial infarction.
abstract: Congestive heart failure developing after acute myocardial infarction (AMI) is a major cause of morbidity and mortality. Clinical trials of cell-based therapy after AMI evidenced only a moderate benefit. We could show previously that suspensions of apoptotic peripheral blood mononuclear cells (PBMC) are able to reduce myocardial damage in a rat model of AMI. Here we experimentally examined the biochemical mechanisms involved in preventing ventricular remodelling and preserving cardiac function after AMI. Cell suspensions of apoptotic cells were injected intravenously or intramyocardially after experimental AMI induced by coronary artery ligation in rats. Administration of cell culture medium or viable PBMC served as controls. Immunohistological analysis was performed to analyse the cellular infiltrate in the ischaemic myocardium. Cardiac function was quantified by echocardiography. Planimetry of the infarcted hearts showed a significant reduction of infarction size and an improvement of post AMI remodelling in rats treated with suspensions of apoptotic PBMC (injected either intravenously or intramoycardially). Moreover, these hearts evidenced enhanced homing of macrophages and cells staining positive for c-kit, FLK-1, IGF-I and FGF-2 as compared to controls. A major finding in this study further was that the ratio of elastic and collagenous fibres within the scar tissue was altered in a favourable fashion in rats injected with apoptotic cells. Intravenous or intramyocardial injection of apoptotic cell suspensions results in attenuation of myocardial remodelling after experimental AMI, preserves left ventricular function, increases homing of regenerative cells and alters the composition of cardiac scar tissue. The higher expression of elastic fibres provides passive energy to the cardiac scar tissue and results in prevention of ventricular remodelling.
authors.affiliation: Department of Thoracic Surgery, Christian Doppler Laboratory for Cardiac and Thoracic Diagnosis and Regeneration, Medical University Vienna, Währinger Gürtel 18-20, Vienna, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Lichtenauer
authors.forename: Michael
authors.initials: M
authors.lastname: Mildner
authors.forename: Andrea
authors.initials: A
authors.lastname: Baumgartner
authors.forename: Matthias
authors.initials: M
authors.lastname: Hasun
authors.forename: Gregor
authors.initials: G
authors.lastname: Werba
authors.forename: Lucian
authors.initials: L
authors.lastname: Beer
authors.forename: Patrick
authors.initials: P
authors.lastname: Altmann
authors.forename: Georg
authors.initials: G
authors.lastname: Roth
authors.forename: Mariann
authors.initials: M
authors.lastname: Gyöngyösi
authors.forename: Bruno Karl
authors.initials: BK
authors.lastname: Podesser
authors.forename: Hendrik Jan
authors.initials: HJ
authors.lastname: Ankersmit
mesh_terms: D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D002921:Cicatrix / Q000378:metabolism; D003094:Collagen / Q000096:biosynthesis; D004452:Echocardiography; D004549:Elastin / Q000096:biosynthesis*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000502:physiology / Q000637:transplantation*; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013535:Suspensions; D020257:Ventricular Remodeling
chemical_list: D013535:Suspensions; D003094:Collagen; D004549:Elastin