title: Effects of pharmacological suppression of plasminogen activator inhibitor-1 in myocardial remodeling after ischemia reperfusion injury.
abstract: Plasminogen activator inhibitor-1 (PAI-1) contributes to cardiac ventricular remodeling because migration of inflammatory cells and attenuation of extracellular matrix degradation are caused by plasmin and matrix metalloproteinase. However, the roles of PAI-1 in myocardial ischemia reperfusion (I/R) injury and the following inflammatory response have not yet been well elucidated. To clarify the role of PAI-1 in myocardial I/R injury, we used a specific PAI-1 inhibitor (IMD-1622) in a rat model. The left anterior descending coronary artery was ligated and reperfusion was performed by loosening the suture after 30 minutes of arterial occlusion. A single administration of IMD-1622 (20 mg/kg) or vehicle was given intraperitoneally and then the rats were sacrificed on day 1 or day 14 after I/R. Blood pressure, echocardiograms, histopathology, and molecular examination were performed. The examinations revealed that PAI-1 inhibitor showed limited effects on cardiac dysfunction and ventricular remodeling after I/R. We conclude that the pharmacological inhibition of PAI-1 may not affect ventricular remodeling after myocardial I/R injury.
authors.affiliation: Department of Cardiovascular Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Watanabe
authors.forename: Takuya
authors.initials: T
authors.lastname: Nakajima
authors.forename: Masahito
authors.initials: M
authors.lastname: Ogawa
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Suzuki
authors.forename: Susumu
authors.initials: S
authors.lastname: Muto
authors.forename: Akiko
authors.initials: A
authors.lastname: Itai
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Hirata
authors.forename: Ryozo
authors.initials: R
authors.lastname: Nagai
authors.forename: Mitsuaki
authors.initials: M
authors.lastname: Isobe
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005500:Follow-Up Studies; D007274:Injections, Intraperitoneal; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D011379:Prognosis; D051381:Rats; D017207:Rats, Sprague-Dawley; D045162:Thiazolidinediones / Q000008:administration & dosage*; D020257:Ventricular Remodeling / Q000187:drug effects / Q000502:physiology*
chemical_list: C530962:3-(3,4-dichlorobenzyl)-5-(3,4,5-trihydroxybenzylidene)thiazolidine-2,4-dione; D017395:Plasminogen Activator Inhibitor 1; D045162:Thiazolidinediones