Signaling pathways that influence extracellular remodeling

Remodeling of myocardial tissue requires a rearrangement of cells and extracellular matrix to form the new geometry through processes that are incompletely defined. Exploring new pathways beyond neurohormonal inhibition is essential for developing new therapies for the growing epidemic of heart failure.

One strategy relies on the discovery that progressive ventricular dilation requires matrix metalloproteinases, a family of enzymes that degrade components of matrix but may also participate in activation or release of signaling molecules. Here we will briefly review evidence that matrix metalloproteinase inhibition represents a potential strategy for preventing heart failure.

Future applications for understanding cell-matrix interactions, including discovering new pathways with proteomics, will also be discussed. Finally, we propose that defining matrix-remodeling events at the level of the membrane and matrix receptors will be essential, and that new bioengineering tools will provide us with the necessary methods.