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p38 MAPK‐dependent MMP regulation during coronary collateral growth
Author(s) -
Dodd Tracy y,
Jadhav Rashmi,
Smith Erika,
Rocic Petra
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.599.16
Subject(s) - matrix metalloproteinase , mmp1 , p38 mitogen activated protein kinases , chemistry , extracellular matrix , western blot , laminin , elastin , medicine , endocrinology , mapk/erk pathway , kinase , pathology , biochemistry , gene expression , gene
We have previously shown that repetitive ischemia (RI) stimulated coronary collateral growth (CCG) in healthy (SD) but not metabolic syndrome (JCR) rats, and required p38 MAPK (p38) activation. Extracellular matrix (ECM) remodeling is associated with CCG, and regulated, in part, by matrix metalloproteinases (MMPs). Thus, we investigated the role of p38 in the regulation of MMP expression and activation in SD vs. JCR rats. An occluder was implanted over the LAD, and the rats underwent the RI protocol (8 40 sec occlusions; every 20 min, every 8 hrs for 0, 3, 6, or 9 days). CCG was measured in the ischemic, collateral‐dependent (CZ) and the normal (NZ) zones using microspheres, p38 activation and MMP expression by Western blot, MMP activity by zymography, and ECM remodeling by immunohistochemistry. SB203580 was given IV to specifically block p38 activation. Expression and activation of MMP1, 2 and 9 were increased on days 3 and 6 of RI in the CZ of SD rats. p38 inhibition decreased MMP 2 and 9 activation. In contrast, RI did not alter expression or activation of MMP1, 2 or 9 in JCR rats. MMP activation correlated with reduced elastin, laminin and type III collagen content. Thus, CCG is dependent on p38‐dependent regulation of MMP expression and activation. Furthermore, compromised CCG in the metabolic syndrome may be partially due to the lack of p38‐dependent MMP activation, and resultant decreased ECM remodeling. NIH RO1 HL093052.