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

Matrix metalloproteinases (MMPs) mediate cell migration and tissue remodeling and are 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.