Osteonectin and osteopontin, two secreted matricellular proteins, have a variety of functions that are exerted through interaction with matrix components. These proteins appear in response to tissue injury. To test our hypothesis that osteopontin and osteonectin are expressed with spatially and temporally different patterns in myocardial infarct tissue, we investigated osteonectin and osteopontin expression in experimentally induced myocardial infarction in rats, in comparison with Type I collagen expression. Northern blotting demonstrated that osteonectin mRNA did not markedly increase on Day 2 after the infarction, but it increased on Days 7 and 14 by 1.7+/-0.12- and 1.8+/-0.01-fold compared to that in preligation hearts. In contrast, osteopontin mRNA was increased on Day 1 (41.9+/-11.3-fold increase) and on Day 2 (58.3+/-7.6-fold increase), and then it declined on Days 7 and 14 (24.8+/-9.0- and 13.5+/-4.7-fold increase, respectively). In situ hybridization revealed that osteonectin mRNA signals were observed in fibroblasts, myofibroblasts and macrophages around infarct necrotic tissue on Days 7 and 14. Osteopontin mRNA signals were observed in macrophages in the infarct marginal zone on Day 2. Immunopositive staining for both osteonectin and osteopontin showed the same pattern as that obtained by in situ hybridization. The time course of osteonectin mRNA was almost parallel with that of Type I collagen mRNA, while that of osteopontin was not. These results demonstrated spatially and temporally different expression patterns of osteonectin and osteopontin in myocardial infarction and suggest that osteonectin appears to be involved in the pathological course in the late phase after infarction concomitantly with Type I collagen, while osteopontin may play a role in the early phase.

No abstract

Objective-To test the hypothesis that changes in serum matrix metalloproteinase-1 (MMP-1) and tissue inhibitors of metalloproteinase-1 (TIMP-1) after acute myocardial infarction reflect extracellular matrix remodelling and the infarct healing process. Patients-13 consecutive patients with their first acute myocardial infarction who underwent successful reperfusion. Methods-Blood was sampled on the day of admission, and on days 2, 3, 4, 5, 7, 14, and 28. Serum MMP-1 and TIMP-1 were measured by one step sandwich enzyme inimunoassay. Left ventricular volume indices were determined by left ventriculography performed four weeks after the infarct. Results-Serum concentrations of both MMP-1 and TIMP-1 changed over time. The average serum MMP-1 was more than 1 SD below the mean control values during the initial four days, increased thereafter, reaching a peak concentration around day 14, and then returned to the middle control range. Negative correlations with left ventricular end systolic volume index and positive correlations with left ventricular ejection fraction were obtained for serum MMP-1 on day 5, when it began to rise, and for the magnitude ofrise in MMP-1 on day 5 compared to admission. Serum TIMP-1 at admission was more than 1 SD below the mean control value, and increased gradually thereafter, reaching a peak on around day 14. Negative correlations with left ventricular end systolic volume index and positive correlations with left ventricular ejection fraction were obtained for serum TIMP-1 on days 5 and 7, and for the magnitude ofrise in TIMP-l on days 5 and 7 compared to admission. Conclusions-Both MMP-1 and TIMP-1 showed significant time dependent alteration after acute myocardial infarction. Thus MMP-1 and TIMP-1 may provide useful information in evaluating the healing process as it affects left ventricular remodelling after acute myocardial infarction. (Heart 1997;78:278-284) Keywords: left ventriculography; ventricular remodelling; matrix metalloproteinase-1; tissue inhibitor of metalloproteinase-1; fibrosis Left ventricular volume is one of the major prognostic factors after acute myocardial infarction.' 2 Ventricular remodelling is thus important with respect to prognosis.34 The extracellular matrix plays a vital role not only in the maintenance of ventricular shape but also in ventricular function. Collagen is apparently an essential component of the extracellular matrix, and collagenases and their inhibitors play crucial roles in extracellular matrix homeostasis.5 Recent biological studies have identified several distinct matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP) and have delineated their characteristics.56 The important roles of MMP and TIMP in cardiovascular disease have been reviewed by Dollery et al.7 MMP-1, a 54 kDa interstitial collagenase, degrades several types of collagen and other extracellular matrix components, including types I and III collagen, the major types of collagen in the collagen matrix.57 TIMP-1, a 29 5 kDa sialoglycoprote...

The present data demonstrated that an increase in expression of HSP47 is produced by spindle-shaped mesenchymal cells in the infarct zone. Expression of HSP47 mRNA was concurrent with the expression of collagen mRNA of types I and III. Hypoxia is one of the factors which induces expression of HSP47.

These observations suggest a positive role in a potentially lower rate of coronary atheroma progression through the administration of olmesartan, an angiotension-II receptor blocking agent, for patients with stable angina pectoris.