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Scott A.
Berceli
M.D., Ph.D. |
RESEARCH INTERESTS:
Multiple interventional strategies have been employed over the last several decades to treat patients with clinically significant arterial stenoses, centered primarily on restoring perfusion to distal arterial beds via bypass grafting or angioplasty. While these therapies have been shown to be effective, their long-term durability is often limited by progressive narrowing within the bypass graft or at the site of the angioplasty. It is this inward remodeling, occurring within the vessel wall in response to the local injury, which limits the durability of these treatments.
An association between arterial remodeling and local hemodynamics has been identified; however the biologic mechanisms underlying this observation are only beginning to be understood. Mechanical shear stress, mediated through the endothelium, has been hypothesized to be the major regulator of vascular remodeling. This biologic process may be divided into two components: the detection of signals by the endothelium due to changes in hemodynamics, and the relay of these signals to adjacent cells within the vessel. Both of these areas have been extensively studied, and the cell-cell signaling pathways provide a potential avenue for intervention in this process.
Dr. Berceli's research focuses on the clinically relevant problem of vein bypass graft failure, and examines the mechanisms underlying accelerated intimal hyperplasia development. Biomechanical forces have been identified as potent regulators of intimal thickening, yet an understanding of the underlying signaling mechanism remains limited. The current work builds on the established rabbit model of flow-regulated vein graft remodeling, focussing on the interactions of various signaling mediators, such as connective tissue growth factor (CTGF) and transforming growth factor (TGF), on assembly and degradation of the extracellular matrix, via matrix metalloproteinases (MMP-2 and -9). Currently gene delivery and antisense oligonucleotide techniques for use in the vascular system are being developed. Insight into these signaling pathways, in combination with development of these powerful gene inhibition techniques, offers the potential for direct application to the clinical setting.
PUBLICATIONS:
1. Clowes AW, Berceli SA: Mechanisms of fibrous cap rupture. Annals of the New York Academy of Science, 902:153-62, 2000
2. Kenagy RD, Fischer JW, Davies MG, Berceli SA, Sandy JD, Hawkins SM, Wight TN, Clowes AW. ADAM-TS and serine proteinase mediated degradation of versican during flow-induced intimal atrophy in baboon PTFE grafts. Arteriosclerosis, Thombosis and Vascular Biology, 22(3):400-4, 2002
3. Jiminez JG, Huber TS, Ozaki CK, Flynn TC, Berceli SA, Lee WA, Seeger JM. Durability of antegrade, prosthetic aortomesenteric bypass for chronic mesenteric ischemia. Journal of Vascular Surgery, 35(6):1078-84, 2002
4. Lee WA, Berceli SA, Huber TS, Seeger JM: Technique for combined hypogastric artery bypass and endovascular repair of complex aortoiliac aneurysms. Journal of Vascular Surgery, 35(6):1289-91, 2002
5. Lee WA, Huber TS, Hirneise CM, Berceli SA, Seeger JM: Eligibility rates of ruptured and symptomatic AAA for endovascular repair. Journal of Endovascular Therapy, 9(4):436-42, 2002
6. Huber TS, Ozaki CK, Flynn TC, Lee WA, Berceli SA, Hirneise CM, Carlton LM, Carter JW, Ross EA, Seeger JM. Prospective validation of an algorithm to maximize arteriovenous fistulae for dialysis access. Journal of Vascular Surgery, 36(3):452-9, 2002.
7. Berceli SA, Davies MG, Kenagy RD, Clowes AW: Flow-induced neointimal regression in baboon PTFE grafts is associated with decreased cell proliferation and increased apoptosis. Journal of Vascular Surgery 36(6):1248-55, 2002
8. Lee WA, Berceli SA, Huber TS, Ozaki CK, Flynn TC, Seeger JM: Morbidity with retroperitoneal procedures during endovascular abdominal aortic aneurysm repair Journal of Vascular Surgery, 38(3):459-65, 2003
9. Jiang Z, Wu L, Miller BL, Goldman DR, Fernandez CM, Abouhamze ZS, Ozaki CK,
Berceli SA: A novel vein graft model: Adaptation to differential flow environments. American Journal of Physiology, 286:H240-45, 2004
10. Berceli SA, Jiang Z, Klingman NV, Pfanhl CL, Abouhamze ZS, Frase CD, Schultz CS, Ozaki CK: Differential expression and activity of MMPs during flow-modulated vein graft remodeling. Journal of Vascular Surgery, 39:1084-90, 2004
11. Jiang Z, Berceli SA, Pfanhl CL, Wu L, Goldman DR, Tao M, Kagayama M, Matsukawa A, Ozaki CK: Wall shear modulation of cytokines in the early vein graft. Journal of Vascular Surgery, in press
12. Jiang Z, Berceli SA, Pfahnl CL, Wu L, Killingsworth CD, Vieira FG, Ozaki CK: Impact of IL-1b on flow induced outward arterial remodeling. Surgery, in press
BOOK CHAPTERS:
1. Berceli SA. Ruptured infrarenal abdominal aortic aneurysm. In: Clinical Scenarios of Vascular Surgery, edited by G Upchuch Jr and P Henke, in press
2. Berceli SA. Management of the Diabetic Foot. In: Mastery of Vascular and Endovascular Surgery, edited by Zelenock, Lumsden, Messina, Moneta, and Huber, in press
3. Ozaki CK, Berceli SA, Irwin AS, Huber TS, Seeger JM, Lee WA, Flynn TC, Palta JR, Mendenhall NP, Zlotecki RA. Radiation therapy for improved dialysis access patency-safety and feasibility. In: Vascular Access for Hemodialysis IX Symposium, 2004, in press
PROCEEDINGS AND ABSTRACTS:
1. Kenagy RD, Sandy J, Davies M, Fisher J, Berceli S, Lemire J, Verscharen C, Westling J, Wight TN, Clowes AW: Versicanase, an aggrecanase-like proteinase that degrades versican, is regulated by flow in baboon aorto-iliac gore-tex grafts. North American Vascular Biology Organization 2000
2. Killingsworth C, Rectenwald JE, Derrow AE, Moldawer LL, Abouhamze Z,
Berceli SA, Huber TS, Seeger JM, Ozaki CK. Direct evidence for TNF-a signaling in arterial remodeling. NIH/Lifeline Foundation Research Initiatives in Vascular Disease, 2001
3. Jiminez JG, Huber TS, Ozaki CK, Flynn TC, Berceli SA, Lee WA, Seeger JM. Durability of antegrade, prosthetic aortomesenteric bypass for chronic mesenteric ischemia. New England Society for Vascular Surgery, 2001
4. Fischer JW, Levkau B, Berceli S, Clowes AW: Cell cycle progression in cultured aortic baboon smooth muscle cells is inhibited by prostacyclin via upregulation of the cyclin-dependent-kinase inhibitor, p27, and down-regulation of cyclin-A and -D1. Circulation, Supplement II, 104:II-178, 2001
5. Huber TS, Ozaki CK, Flynn TC, Lee WA, Berceli SA, Hirneise CM, Carlton LM, Ross EA, Seeger JM. Prospective validation of an algorithm to maximize arteriovenous fistulae for dialysis access. Southern Association for Vascular Surgery, 2002.
6. Bray E, Didier N, Perrault C, Tran-Son-Tay R, Ozaki CK. Altered leukocyte rheology in diabetes mellitus. Arteriosclerosis, Thrombosis and Vascular Biology, 2002
7. Jiang Z, Bray E, Abouhamze Z, Berceli SA, Ozaki CK. Simplified Rabbit Jugular Vein Graft Interposition Model. Arteriosclerosis, Thrombosis and Vascular Biology, 2002
8. Kenagy RD, Sandy J, Davies M, Fisher J, Berceli S, Lemire J, Verscharen C, Westling J, Wight TN, Clowes AW:ADAM-TS and Plasmin Mediated Degradation of Versican during Flow-Induced Intimal Atrophy in Baboon Polytetrafluorethylene (PTFE) Grafts. Arteriosclerosis, Thombosis and Vascular Biology, 2002
9. Jiang Z, Frase C, Abouhamze ZS, Wu L, Ozaki CK, Berceli SA. The temporal impact of flow on vein graft remodeling. Association of Academic Surgery, 2002.
10. Jiang Z, Frase C, Pfahnl CL, Abouhamze ZS, Wu L, Berceli SA, Ozaki CK. Flow modulates IL-1b expression and neointimal hyperplasia in a novel vein graft model. Circulation, Supplement, 2002
11. Ozaki CK, Jiang Z, Pfanhl CL, Abouhamze ZS, Wu L, Miller BL, Goldman DR, Vieira FG, Killingsworth CD,
Berceli SA: Impact of IL-1b on flow induced outward remodeling. Society of University Surgeons, 2004.
12. Ozaki CK, Berceli SA, Irwin AS, Huber TS, Seeger JM, Flynn TS, Lee WA, Palta J, Mendenhall NP, Zlotecki RA: Radiation Therapy for Improved Dialysis Patency - Safety and Feasibility. Vascular Access for Hemodialysis IX Symposium, 2004.
PRESENTATIONS:
1. Berceli SA, Davies M, Clowes AW: Arterial flow and hemodynamics - Signaling in the vessel wall in the whole animal", Invited Faculty, Lifeline/NIH Initiatives in Vascular Surgery, Bethesda, MD, March 2, 2001
2. Berceli SA, Jiang Z, Klingman N, Pfahnl C, Abouhamze Z, Frase C, Ozaki CK: Differential expression and activity of MMPs during flow-modulated vein graft remodeling. Lifeline/NIH Initiatives in Vascular Surgery, Bethesda, MD, April 3-4, 2003
3. Berceli SA, Jiang Z, Blalock T, Pfahnl C, Schultz G, Ozaki CK: Connective Tissue Growth Factor in Flow-Regulated Vein Graft Intimal Hyperplasia. Association of Academic Surgery Annual Meeting, Sacramento, CA, November 13-15, 2003
4. Fernandez CM, Goldman DR, Jiang Z, Ozaki CK, Trans-Son-Tay R, Berceli
SA: Impact of Shear Stress on Early Vein Graft Remodeling: A Biomechanical Analysis. International Society for Applied Cardiovascular Biology, Savannah, GA, March 11-13, 2004
5. Berceli SA, Jiang Z, Klingman N, Ozaki CK, Schultz G: Flow Regulation of MMP-2 and - 9 During Arterial and Vein Graft Remodeling. Vascular 2004, Anaheim, CA, June 2-6, 2004
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