Macrophage depletion in hypertensive rats accelerates development of cardiomyopathy.
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.
Zandbergen
Harmen R
HR
University Hospital Maastricht and Cardiovascular Research Institute Maastricht, Maastricht, Netherlands.
Sharma
Umesh C
UC
Gupta
Sudhir
S
Verjans
Johan W H
JW
van den Borne
Susanne
S
Pokharel
Saraswati
S
van Brakel
Thomas
T
Duijvestijn
Adriaan
A
van Rooijen
Nico
N
Maessen
Jos G
JG
Reutelingsperger
Chris
C
Pinto
Yigal M
YM
Narula
Jagat
J
Hofstra
Leo
L
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
D008081:Liposomes; C473112:Ren2 protein, mouse; D004002:Clodronic Acid; D012083:Renin