title: Macrophage depletion in hypertensive rats accelerates development of cardiomyopathy.
abstract: Inflammation contributes to the process of ventricular remodeling after acute myocardial injury. To investigate the role of macrophages in the chronic process of cardiac remodeling, they were selectively depleted by intravenous administration of liposomal clodronate in heart failure-prone hypertensive Ren-2 rats from the age of 7 until 13 weeks. Plain liposomes were used for comparison. Liposomal clodronate treatment reduced the number of blood monocytes and decreased the number of macrophages in the myocardium. Compared to plain liposomes, liposomal clodronate treatment rapidly worsened left ventricular ejection function in hypertensive rats. Liposomal clodronate- treated Ren-2 rat hearts showed areas of myocyte loss with abundant inflammatory cell infiltration, predominantly comprising CD4 positive T lymphocytes. The current study showed that lack of macrophages was associated with earlier development of myocardial dysfunction in hypertensive rats. Modulation of macrophage function may be of value in the evolution of cardiomyopathy.
authors.affiliation: University Hospital Maastricht and Cardiovascular Research Institute Maastricht, Maastricht, Netherlands.
authors.forename: Harmen R
authors.initials: HR
authors.lastname: Zandbergen
authors.forename: Umesh C
authors.initials: UC
authors.lastname: Sharma
authors.forename: Sudhir
authors.initials: S
authors.lastname: Gupta
authors.forename: Johan W H
authors.initials: JW
authors.lastname: Verjans
authors.forename: Susanne
authors.initials: S
authors.lastname: van den Borne
authors.forename: Saraswati
authors.initials: S
authors.lastname: Pokharel
authors.forename: Thomas
authors.initials: T
authors.lastname: van Brakel
authors.forename: Adriaan
authors.initials: A
authors.lastname: Duijvestijn
authors.forename: Nico
authors.initials: N
authors.lastname: van Rooijen
authors.forename: Jos G
authors.initials: JG
authors.lastname: Maessen
authors.forename: Chris
authors.initials: C
authors.lastname: Reutelingsperger
authors.forename: Yigal M
authors.initials: YM
authors.lastname: Pinto
authors.forename: Jagat
authors.initials: J
authors.lastname: Narula
authors.forename: Leo
authors.initials: L
authors.lastname: Hofstra
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D009202:Cardiomyopathies / Q000276:immunology* / Q000503:physiopathology; D004002:Clodronic Acid / Q000008:administration & dosage; D004195:Disease Models, Animal; D018450:Disease Progression; D006973:Hypertension / Q000150:complications / Q000276:immunology* / Q000503:physiopathology; D007275:Injections, Intravenous; D008081:Liposomes; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D008297:Male; D009000:Monocytes / Q000276:immunology; D009206:Myocardium / Q000276:immunology* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D012083:Renin / Q000235:genetics; D013318:Stroke Volume; D013997:Time Factors; D016277:Ventricular Function, Left; D020257:Ventricular Remodeling
chemical_list: D008081:Liposomes; C473112:Ren2 protein, mouse; D004002:Clodronic Acid; D012083:Renin