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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:1119.)
© 2005 American Heart Association, Inc.

Brief Reviews

Extracellular Proteases in Atherosclerosis and Restenosis

Arturo Garcia-Touchard; Timothy D. Henry; Giuseppe Sangiorgi; Luigi Giusto Spagnoli; Alessandro Mauriello; Cheryl Conover; Robert S. Schwartz

From Minnesota Cardiovascular Research Institute (A.G.-T., T.D.H., R.S.S.), Minneapolis Heart Institute, Minneapolis, Minn; Anatomic Pathology Division and Department of Cardiovascular Disease (G.S.), University of Rome Tor Vergata, Rome, Italy; Anatomic Pathology Division (L.G.S., A.M.), University of Rome Tor Vergata, Rome, Italy; and Endocrine Research Unit (C.C.), Mayo Clinic and Foundation. Rochester, Minn.

Correspondence to Robert S. Schwartz, MD, FACC, Minneapolis Heart Institute. Minnesota Cardiovascular Research Institute 928 E. 28^th St, Minneapolis, MN 55407. E-mail rss{at}rsschwartz.com

Extracellular proteolysis plays a key role in many pathophysiologic processes including cancer, inflammatory diseases, and cardiovascular conditions such as atherosclerosis and restenosis. Whereas matrix metalloproteinases are their best known member, many others are becoming better known. The extracellular proteases are a complex and heterogeneous superfamily of enzymes. They include metalloproteinases (matrix metalloproteinases, adamalysins, or pappalysins), serine proteases (elastase, coagulation factors, plasmin, tissue plasminogen activator, urokinase plasminogen activator), and the cysteine proteases (such cathepsins). In addition to their matrix degradation capabilities, they have other less well known biologic functions that include angiogenesis, growth factor bioavailability, cytokine modulation, receptor shedding, enhancing cell migration, proliferation, invasion, and apoptosis. This review discusses extracellular proteases relevant to the vasculature, their classification and function, and how protease disorders contribute to arterial plaque growth, including chronic atherosclerosis, acute coronary syndromes, restenosis, and vascular remodeling. These broad extracellular protease functions make them potentially interesting therapeutic targets.

Extracellular proteases are a complex and heterogeneous family of enzymes involved in many important biological functions. This review discusses the extracellular proteases relevant to the vasculature, their functions, and how protease disorders can contribute to plaque growth, including chronic atherosclerosis, acute coronary syndromes, restenosis, and vascular remodeling.

Key Words: acute coronary syndromes • aneurysms • athersclerosis • proteases • restenosis

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