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.
Baghelai
K
K
Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia, 23298, USA.
Marktanner
R
R
Dattilo
J B
JB
Dattilo
M P
MP
Jakoi
E R
ER
Yager
D R
DR
Makhoul
R G
RG
Wechsler
A S
AS
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