Scar and pulmonary expression and shedding of ACE in rat myocardial infarction.
We examined the topology of angiotensin-converting enzyme (ACE) mRNA expression, activity, and shedding in myocardial infarction-induced heart failure and sought to elucidate the source of the increased plasma ACE activity in this model. Three months after coronary ligature, lung, scar, and remaining viable left ventricular tissues were analyzed for ACE mRNA expression as well as tissue and solubilized ACE activity. ACE mRNA expression increased in the scar with respect to infarct severity, decreased in the lung, and remained unchanged in the left ventricle. ACE activity decreased in the lung and increased in the scar tissue and plasma. Shedding of ACE remained constant in the lung and increased in the scar. This study shows that ACE expression and activity is shifted from the pulmonary endothelium to the infarct scar tissue and that constancy of shedding in the lung and its increase in the scar are the source of the increased plasma ACE in congestive heart failure.
Gaertner
Roger
R
Cardiovascular Research Department, Institut National de la Santé et de la Recherche Médicale, 75018 Paris, France.
Prunier
Fabrice
F
Philippe
Monique
M
Louedec
Liliane
L
Mercadier
Jean-Jacques
JJ
Michel
Jean-Baptiste
JB
D000818:Animals; D004151:Dipeptides / Q000494:pharmacology; D004195:Disease Models, Animal; D004452:Echocardiography; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D015870:Gene Expression; D006333:Heart Failure / Q000209:etiology / Q000473:pathology; D006352:Heart Ventricles / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008168:Lung / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009203:Myocardial Infarction / Q000150:complications / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D009929:Organ Size; D007703:Peptidyl-Dipeptidase A / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D011480:Protease Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D004151:Dipeptides; C078131:N-(2(R)-2-(hydroxamidocarbonylmethyl)-4-methylpentanoyl)-L-tryptophan methylamide; D011480:Protease Inhibitors; D012333:RNA, Messenger; D007703:Peptidyl-Dipeptidase A