Iwona Fijalkowska and Rubin M Tuder

Divisions of Cardiopulmonary Pathology and Pulmonary and Critical Medicine, Departments ofPathology and Medicine, Johns

Hopkins University School of Medicine, Baltimore, Maryland


As important as the inner organelles of the cell, the extracellular matrix (ECM) plays fundamental roles in cell function. The molecular framework of the extracellular matrix serves several functions in cell-to-cell communication and integration of environmental cues to a cell's differentiation and fate. We have learned that the extracellular matrix is as plastic and dynamic as the cells that produce them. Critical in this molecular and structural plasticity is the ability to cleave the underlying molecular matrix units, which is accomplished by a vast array of enzymes with a wide spectrum of substrate specificities. Metalloproteases (MMPs) or matrixins refer to a wide superfamily of enzymes that requires the presence of a highly conserved zinc-binding motif for catalysis [1, 2]. MMPs are functionally, structurally, and at the DNA sequence homology related to a collagenase found in the tail of a tadpole undergoing metamorphosis, which was the first member to be described within this rapidly expanding superfamily of enzymes. By cleaving the molecular extracellular framework surrounding cells, MMPs contribute to cell renewal and tissue formation, both in the embryo and in the adult system. Their action continues in critical biological processes, such as tissue remodeling, would healing, and angiogenesis. Furthermore, there is growing evidence that, despite their enzymatic activity, MMPs also act as cellular regulatory factors in areas of cellular signaling, growth, differentiation, and death. These broad functions modulate or control interactions of a cell with its immediate surroundings and with its external environment.

In this chapter, the authors aim at summarizing the newest knowledge on the role of MMPs in physiological and pathophysiological processes, with an emphasis in vascular and pulmonary vascular biology.

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