Integrins: novel therapeutic targets for cardiovascular diseases.
Integrins are the principle mediators of molecular dialog between a cell and its extracellular matrix environment. The unique combinations of integrin subunits determine which extracellular matrix molecules are recognized by a cell. Recent studies have demonstrated that remodeling in heart and vasculature is linked to alterations in extracellular matrix and integrin expression. The roles of integrins in controlling cellular behavior have made these molecules highly attractive drug targets. New insights into mechanisms whereby the extracellular matrix takes part in the control of smooth muscle cell proliferation and cardiac growth suggest a number of putative targets for future therapies that can be applied to increase plaque stability, prevent the clinical consequences of atherosclerosis and improve outcomes after interventional procedures such as cardiac transplantation. Therapeutic candidates include antibodies, cyclic peptides, peptidomimetics and small molecules. The integrin inhibitors Integrilin and ReoPro have been approved as blood thinners in cardiovascular disease, and newer agents are undergoing testing. Although integrin function is important in the cardiovascular system, there are wide gaps in knowledge. In this review, we discuss the primary mechanisms of action and signaling of integrins in the cardiac and vascular system in normal and pathological states, as well as therapeutic strategies for targeting these molecules in the cardiovascular system.
Lal
Hind
H
Division of Molecular Cardiology, Cardiovascular Research Institute, The Texas A&M University System Health Science Center, College of Medicine, Temple TX 76504, USA.
Guleria
Rakeshwar S
RS
Foster
Donald M
DM
Lu
Guangrong
G
Watson
Linley E
LE
Sanghi
Sandhya
S
Smith
Manuela
M
Dostal
David E
DE
D002317:Cardiovascular Agents / Q000737:chemistry / Q000494:pharmacology*; D002318:Cardiovascular Diseases / Q000188:drug therapy*; D002320:Cardiovascular Physiological Phenomena; D004730:Endothelium, Vascular / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D016023:Integrins / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism; D016032:Randomized Controlled Trials as Topic; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D002317:Cardiovascular Agents; D016023:Integrins