Molecular and cellular events at the site of myocardial infarction: from the perspective of rebuilding myocardial tissue.
The potential for bone marrow-derived progenitor cells (BMDPC) to regenerate myocardial tissue following infarction depends on homing, migration, nourishment, and spatially appropriate growth of BMDPC. Requisite to these objectives is the expression of adhesion molecules (ICAM-1) and chemoattractant cytokines (MCP-1), matrix metalloproteinase (MMP) activity, a neovasculature, and fibrillar collagen scaffolding. We found that enhanced ICAM-l and MCP-1, as well as MMP activity on day 3 and 7 postMI, are present to facilitate the homing, chemotaxis, and migration of circulating cells into the infarct site. The vascular network formed at the infarct site contains a ratio of conduit to exchange vessels that is greater than that for control tissue and therefore its ability to nourish BMDPC for their growth appears to be tenuous. These findings, together with the dense formation of a fibrillar collagen scar beyond week 2, suggest the optimal time to rebuild myocardium from BMDPC resides within 2 week postMI.
Lu
Li
L
Division of Cardiovascular Diseases, Department of Medicine, University of Tennessee, Health Science Center, Memphis, TN, USA.
Zhang
John Q
JQ
Ramires
Felix J
FJ
Sun
Yao
Y
D000818:Animals; D006348:Cardiac Surgical Procedures / Q000379:methods; D018932:Chemokine CCL2 / Q000378:metabolism*; D004789:Enzyme Activation; D005109:Extracellular Matrix / Q000378:metabolism*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012038:Regeneration / Q000502:physiology; D014018:Tissue Distribution; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism*; D014945:Wound Healing / Q000502:physiology*
D018932:Chemokine CCL2; D019715:Tissue Inhibitor of Metalloproteinase-1; D018799:Intercellular Adhesion Molecule-1