on March 31, 2005
Published online before print March 31, 2005, doi: 10.1161/01.ATV.0000164311.48592.da
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Submitted on November 23, 2004
Accepted on March 18, 2005
Extracellular Proteases in Atherosclerosis and Restenosis
Arturo Garcia-Touchard ;
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.
* To whom correspondence should be addressed. E-mail: rss{at}rsschwartz.com.
Abstract--Extracellular proteolysis plays a key role in many pathophysiologic processes including cancer, inflammatory diseases, and cardiovascular conditions such as atherosclerosis and restenosis. Whereas matrix metalloproteases are their best known member, many others are becoming better known. The extracellular proteases are a complex and heterogeneous superfamily of enzymes. They include metalloproteases (matrix metalloproteases, 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.
Key words: acute coronary syndromes • aneurysms • athersclerosis • proteases • restenosis
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