Expression of tissue inhibitor of metalloproteinases (TIMPs) during early cardiac development

Matrix metalloproteinases (MMPs) mediate cell migration and tissue remodeling and a-re important in cardiac development. We examined the expression patterns of two MMP inhibitors, tissue inhibitor of metalloproteinase (TIMP)-2 and TIMP-3, during critical stages of cardiac development, Both TIMP-2 and TIMP-3 mRNA were expressed in the endocardium prior to and during early cushion cell formation. TIMP-2 was continually expressed within the outflow tract (OT) and atrioventricular (AV) cushion cells at all stages examined, whereas TIMP-3 mRNA was undetectable in the AV cushion cells soon after their formation. Subsequently, TIMP-3 mRNA disappeared in cushion cells of the distal OT and this loss progressed toward the ventricle until eventually all of the OT cushion cells lacked detectable TIMP-3 transcripts. TIMP-3, but not TIMP-2, was also expressed within remodeling myocardium. Immunocytochemistry confirmed these findings. These observations suggest that TIMP-2 and TIMP-3 have important but unique roles in early cardiac development. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.