Decreased expression of tissue inhibitor of metalloproteinase 1 in stunned myocardium.
Ultrastructural studies of stunned myocardium have shown disorganization and loss of extracellular collagen and increased collagenase activity early after ischemia and reperfusion. The interplay between matrix metalloproteinase 1 (MMP-1) and tissue inhibitor of metalloproteinase 1 (TIMP-1) regulates the turnover of cardiac extracellular matrix fibrillar collagens. However, the gene expression of MMP-1 and TIMP-1 in stunned myocardium is not known. Here, we determined whether altered expression of MMP-1 and TIMP-1 occurs in globally stunned hearts. An isolated nonworking rabbit heart preparation, perfused with a bovine erythrocyte suspension in modified Krebs solution, was used. Two groups were studied: the stunned group was subjected to 20 min of normothermic global ischemia followed by 120 min of normal reperfusion (n = 8), and the control group underwent 140 min of uninterrupted perfusion (n = 7). The developed pressures at the end of reperfusion for ischemic and control hearts were 67.0 +/- 2.73 and 83.1 +/- 1.52 mm Hg (P < 0. 006) respectively. Ribonuclease protection assays of total left ventricular RNA using riboprobes for MMP-1, TIMP-1, and 18S rRNA were performed. A significant decrease (twofold, P < 0.03) in TIMP-1 gene expression was found in the stunned hearts, while MMP-1 mRNA expression was unchanged. Thus, in early stunning, the decrease in TIMP-1 expression could tip the balance favoring enhanced metalloproteinase activity, promoting collagen turnover, and initiating extracellular matrix remodeling. This may contribute to delayed recovery from myocardial stunning.
Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia, 23298, USA.
K
K
Baghelai
R
R
Marktanner
J B
JB
Dattilo
M P
MP
Dattilo
E R
ER
Jakoi
D R
DR
Yager
R G
RG
Makhoul
A S
AS
Wechsler
D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D002417:Cattle; D017364:Collagenases / Q000235:genetics / Q000378:metabolism; D003971:Diastole; D015870:Gene Expression / Q000502:physiology; D066298:In Vitro Techniques; D020781:Matrix Metalloproteinase 1; D017682:Myocardial Stunning / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D009693:Nucleic Acid Hybridization; D012333:RNA, Messenger / Q000378:metabolism; D012337:RNA, Ribosomal, 18S / Q000378:metabolism; D011817:Rabbits; D012260:Ribonucleases; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism*
D012333:RNA, Messenger; D012337:RNA, Ribosomal, 18S; D019715:Tissue Inhibitor of Metalloproteinase-1; D012260:Ribonucleases; D017364:Collagenases; D020781:Matrix Metalloproteinase 1