Randolph L. Geary, M.D., FACS, Professor of Surgery - Vascular Surgery
Professor of Pathology - Comparative Medicine
Dr. Geary was recruited to Wake Forest in 1994 from the University of Washington, Seattle, where he completed medical school, general surgery residency and a vascular surgery fellowship. While in Seattle, Dr. Geary was awarded an American Heart Association post-doctoral research fellowship in the laboratory of Alexander W. Clowes, M.D., working on regulation of vascular smooth muscle cell growth by blood flow and shear stress as well as on viral vectors for vascular gene transfer. He is currently Professor of Surgery with cross-appointments in the Departments of Pathology - Comparative Medicine and the Wake Forest Institute for Regenerative Medicine. Dr. Geary is active in vascular research exploring how atherosclerotic arteries heal following reconstruction and has a busy clinical practice in vascular surgery.

SYNOPSIS OF AREA OF INTEREST:: Arterial injury and repair, constrictive artery wall remodeling, restenosis and blood vessel bioengineering.

DETAILED AREA OF INTEREST: Virtually all forms of arterial reconstruction result in mechanical injury to the artery wall, which stimulates a cascade of injury responses as the vessel heals. In many patients the injury response is excessive, leading to recurrent narrowing of the artery at the site of repair. This is termed "restenosis." Restenosis is an enormous public heath issue given millions of arterial revascularization procedures are performed each year and about one third will fail from restenosis within 2 years (e.g., following angioplasty, stenting, endarterectomy, or arterial bypass). Restenosis has two basic underlying structural explanations - new tissue formation and shrinkage of the artery wall from inward constriction. New tissue forms from hyperplasia of smooth muscle cells in response to cytokines and growth factors released at sites of injury. New artery wall mass then accumulates inside the artery where is can encroach the lumen. As the artery wall heals it may also shrink by reorganizing pre-existing wall components (cells and extra-cellular matrix) into a smaller geometry. This constrictive remodeling is analogous to wound contraction and fibrosis and can also lead to lumen encroachment. While much is known about the regulation of smooth muscle cell hyperplasia, little is known about the molecular regulation of artery wall remodeling and constriction. Our lab is studying the effects of various matrix components on tissue contraction. Specifically, we are studying the interaction between cells, collagen, and hyaluronic acid - a prominent component of the matrix secreted by smooth muscle cells as they repair the injured artery wall. It is unclear whether hyaluronan improves or impairs reorganization of collagen following injury. To address this question we are studying the injury response in atherosclerotic primates treated with peri-arterial hyaluronan and also the effects of genetic deletion of specific hyaluronan receptors in knockout mice and effects on the response to injury. The overarching goal is to identify molecular targets to block constrictive remodeling after arterial reconstruction as a means of preventing restenosis. Our lab is also collaborating with WFIRM on characterizing the in vivo responses of bioengineered blood vessels. Many parallels are likely in the healing of bioengineered arteries and the injury response in native arteries. By manipulating cells and scaffoldings used in constructing bioengineered blood vessels, we may be able to alter healing responses to improve vessel maturation.

PUBLICATIONS:

Pearce JD, Li J, Edwards MS, English WP, Geary RL: Differential effects of Rho-kinase inhibition on artery wall mass and remodeling. J. Vasc Surg 2004;39:223-228.

Li J, Adams LD, Wang X, Pabon L, Schwartz SM, Sane DC, Geary RL: Regulator of G-protein signaling 5 (RGS5) marks peripheral arterial smooth muscle cells and is down-regulated in atherosclerotic plaque. J Vasc Surg 2004;40:519-28.

Bergt C, Pennathur S, Fu X, Byun J, Singh P, McDonald TO, O'Brien K, Chait A, Brunzell J, Geary RL, Oram JF, Anantharamaiah GM, Heinecke JW. The myeloperoxidase product hypochlorous acid oxidizes HDL in the human artery wall and impairs ABCA1-dependent cholesterol transport. Proc Natl Acad Sci U S A. 2004;101:13032-7. Epub 2004 Aug 23.

Adams LD, Geary RL, Li J, Rossini A, Schwartz SM. Expression Profiling Identifies Smooth Muscle Cell Diversity Within Human Intima and Plaque Fibrous Cap. Loss of RGS5 Distinguishes the Cap. Arterioscler Thromb Vasc Biol. 2005 Nov 17; epub ahead of print. vessel maturation.

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