Research Profile
The Division of Vascular Surgery has an active research program that spans basic to clinical studies and offers opportunities for trainees at all levels.
There is a basic science laboratory located at the Harvard Institutes of Medicine, 4th floor, which is an integral part of the Harvard Gene Therapy Initiative. The primary theme has centered on the application of genetic strategies (gene transfer, gene blockade) to modify the vascular injury response. The specific area of greatest interest is the re-engineering of vein bypass grafts that are resistant to failure. Current projects include: 1) ongoing evaluation of novel vector systems and approaches to achieve safe and efficient gene delivery to vein grafts in an intraoperative setting; and 2) studies on the factors that control smooth muscle cell differentiation and growth in the healing vein graft. These efforts are currently supported by an active K08 award from NHLBI and the Lifeline Foundation. Lab fellows have successfully competed, and been supported by, the NIH-supported Longwood Area Vascular Research Training Grant (T32) on which Dr. Conte is one of the participating faculty.
The translational research program in vein graft disease extends into the clinical research arena as well. We have recently initiated an NIH-supported (R01), prospective longitudinal study to examine the influence of inflammation on the outcomes of patients undergoing lower extremity bypass for advanced limb ischemia, and to examine the mechanisms of graft healing using high resolution imaging (MR and ultrasound). This study offers numerous potential opportunities for subprojects.
Other ongoing clinical research projects focus on the assessment of outcomes following all types of vascular reconstructions (the division maintains a large prospective registry), as well as ongoing studies of endoluminal devices and therapies, and their impact on vascular care. Opportunities for focused clinical projects are available for trainees.
Back to the top
Projects
1. Survivin: A Novel Regulator of Intimal Hyperplasia and Vein Graft Remodling
Failure of vascular interventions, including angioplasty, stenting, and bypass surgery, frequently results from an exaggerated healing response in the vessel wall, leading to narrowing and occlusion. This process is characterized by the formation of intimal hyperplasia (IH), a lesion consisting primarily of smooth muscle cells (SMC) bearing a proliferative, synthetic, and de-differentiated phenotype. Recent evidence suggests that surviving (SVV), a novel protein which regulates both apotosis and poroliferation, may be an important therapeutic target in disorders characterized by dysregulated growth, such as cancer and IH. In this translational research proposal, Dr. Conte’s lab seeks to validate SVV as a molecular target in IH, most particularly in the context of vein graft failure. First, they will investigate approaches to directly inhibit SVV gene expression, in-vitro and in-vivo. The effects of SVV knockdown on SMC phenotype and vein graft hyperplasia will be determined. In the second specific aim, they will explore the therapeutic relevance of the interaction between SVV and heat shock protein 90 (Hsp90), a molecular chaperone, using a peptide-based approach to disrupt this critical protein-protein interaction. Finally in the third aim, they will investigate whether anti-SVV molecular strategies may sensitize vascular SMC to the pro-apoptotic effects of statin drugs, potentially expanding the therapeutic utility of these atheroprotective drugs to extend the benefits of vascular interventions.
Vein bypass surgery, currently employed in some 500,000 cases annually in the United States, is a critical life- or limb-sparing intervention for many patients afflicted with cardiovascular disease. Although often effective, vein bypass grafts are subject to a significant rate of failure over time (30-50% within five years), leading directly to mortality, limb amputation, and diminished quality of life. Dr. Conte seeks to broaden the understanding of factors which are involved in vein graft failure, and will examine a novel approach to reengineer bypass grafts that may be resistant to occlusion. His studies also have direct relevance for improving the long-term results of other cardiovascular interventions such as percutaneous angioplasty and stenting, by providing new molecular approaches to control the vascular injury response.
Back to the top
Labs
Vascular Surgery Research Laboratory
A multidisciplinary approach to the study of vascular disease. We are focusing mainly on the molecular mechanisms and potential therapeutic targets which govern lower extremity bypass graft failure, restenosis and hypertension
Back to the top
Funding
1. Principal Investigator: Michael Conte, M.D.
Source: NIH
Title of Project: Survivin: A Novel Regulator of Intimal Hyperplasia and Vein Graft Remodeling
Project Period: 08/01/07 - 06/30/2012
2. Principal Investigator: Michael Conte, M.D.
Source: Angiotech Pharmaceuticals, Inc.
Title of Project: Randomized Single Blind Trial to Assess the Effectiveness of Maintaining Patency and Safety of the Vascular Wrap(TM) Paclitaxel-Eluting Mesh After Surgical Implantation with the Lifespan(R) ePTFE Vascular Graft in the Upper Extremity for Hemodialysis Vascular Access
3. Principal Investigator: Michael Conte, M.D.
Source: Pervasis Therapeutics, Inc.
Title of Project: Safety of Vascugel(TM) Treatment after the Creation of Arteriovenous Access for Hemodialysis Use.
Project Period: 11/19/06 - 11/08/08
Back to the top
Publications
For the latest articles by Dr. Michael Conte, please visit 
.
Mitsouras D, Mulkern RV, Owens CD, Conte MS, Ersoy H, Luu TM, Whitmore AG, Creager MA, Rybicki FJ. High-resolution peripheral vein bypass graft wall studies using high sampling efficiency inner volume 3D FSE. Magn Reson Med. 2008 Mar;59(3):650-4.
Conte MS. Buflomedil in peripheral arterial disease: trials and tribulations. Circulation. 2008 Feb 12;117(6):717-9.
Brahmanandam S, Ding EL, Conte MS, Belkin M, Nguyen LL. Clinical results of carotid artery stenting compared with carotid endarterectomy. J Vasc Surg. 2008 Feb;47(2):343-9.
Nguyen LL, Brahmanandam S, Bandyk DF, Belkin M, Clowes AW, Moneta GL, Conte MS. Female gender and oral anticoagulants are associated with wound complications in lower extremity vein bypass: an analysis of 1404 operations for critical limb ischemia. J Vasc Surg. 2007 Dec;46(6):1191-1197.
Schanzer A, Hevelone N, Owens CD, Belkin M, Bandyk DF, Clowes AW, Moneta GL, Conte MS. Technical factors affecting autogenous vein graft failure: observations from a large multicenter trial. J Vasc Surg. 2007 Dec;46(6):1180-90; discussion 1190.
Rybicki FJ, Mitsouras D, Owens CD, Whitmore AG, Ersoy H, Mulkern RV, Creager MA, Conte MS. Lower extremity peripheral vein bypass graft wall thickness changes demonstrated at 1 and 6 months after surgery with ultra-high spatial resolution black blood inner volume three-dimensional fast spin echo magnetic resonance imaging. Int J Cardiovasc Imaging. 2007 Dec 14
Hoel AW, Wang GJ, Simosa HF, Conte MS. Regulation of vascular smooth muscle cell growth by survivin. Vascular. 2007 Nov-Dec;15(6):344-9.
Berceli SA, Hevelone ND, Lipsitz SR, Bandyk DF, Clowes AW, Moneta GL, Conte MS. Surgical and endovascular revision of infrainguinal vein bypass grafts: analysis of midterm outcomes from the PREVENT III trial. J Vasc Surg. 2007 Dec;46(6):1173-1179. Epub 2007 Oct 22.
Hoel AW, Conte MS. Edifoligide: a transcription factor decoy to modulate smooth muscle cell proliferation in vein bypass. Cardiovasc Drug Rev. 2007 Fall;25(3):221-34. Review.
Conte MS. Molecular engineering of vein bypass grafts. J Vasc Surg. 2007 Jun;45 Suppl A:A74-81. Review
Schanzer A, Hoel A, Owens CD, Wake N, Nguyen LL, Conte MS, Belkin M. Restenosis after carotid endarterectomy performed with routine intraoperative duplex ultrasonography and arterial patch closure: a contemporary series. Vasc Endovascular Surg. 2007 Jun-Jul;41(3):200-5.
Owens CD, Ho KJ, Kim S, Schanzer A, Lin J, Matros E, Belkin M, Conte MS. Refinement of survival prediction in patients undergoing lower extremity bypass surgery: stratification by chronic kidney disease classification. J Vasc Surg. 2007 May;45(5):944-52. Epub 2007 Mar 28.
Schanzer A, Owens CD, Conte MS, Belkin M. Superficial femoral artery percutaneous intervention is an effective strategy to optimize inflow for distal origin bypass grafts. J Vasc Surg. 2007 Apr;45(4):740-3.
Owens CD, Ridker PM, Belkin M, Hamdan AD, Pomposelli F, Logerfo F, Creager MA, Conte MS. Elevated C-reactive protein levels are associated with postoperative events in patients undergoing lower extremity vein bypass surgery. J Vasc Surg. 2007 Jan;45(1):2-9; discussion 9. Epub 2006 Nov 21.
Nguyen LL, Moneta GL, Conte MS, Bandyk DF, Clowes AW, Seely BL; PREVENT III Investigators. Prospective multicenter study of quality of life before and after lower extremity vein bypass in 1404 patients with critical limb ischemia. J Vasc Surg. 2006 Nov;44(5):977-83; discussion 983-4.
Nguyen LL, Lipsitz SR, Bandyk DF, Clowes AW, Moneta GL, Belkin M, Conte MS. Resource utilization in the treatment of critical limb ischemia: The effect of tissue loss, comorbidities, and graft-related events. J Vasc Surg. 2006 Nov;44(5):971-5; discussion 975-6.
Owens CD, Wake N, Jacot JG, Gerhard-Herman M, Gaccione P, Belkin M, Creager MA, Conte MS. Early biomechanical changes in lower extremity vein grafts-distinct temporal phases of remodeling and wall stiffness. J Vasc Surg. 2006 Aug 19;
Conte MS, Altieri DC. Survivin regulation of vascular injury. Trends Cardiovasc Med. 2006 May;16(4):114-7.
Conte MS, Bandyk DF, Clowes AW, Moneta GL, Seely L, Lorenz TJ, Namini H, Hamdan AD, Roddy SP, Belkin M, Berceli SA, DeMasi RJ, Samson RH, Berman SS; PREVENT III Investigators. Results of PREVENT III: a multicenter, randomized trial of edifoligide for the prevention of vein graft failure in lower extremity bypass surgery. J Vasc Surg. 2006 Apr;43(4):742-751; discussion 751.
Cunningham LD, Conte MS. Lower-extremity arterial disease.Perspect Vasc Surg Endovasc Ther. 2005 Dec;17(4):351-61.
Chew DK, Nguyen LL, Owens CD, Conte MS, Whittemore AD, Gravereaux EC, Menard MT, Belkin M. Comparative analysis of autogenous infrainguinal bypass grafts in African Americans and Caucasians: the association of race with graft function and limb salvage. J Vasc Surg. 2005 Oct;42(4):695-701.
Wang GJ, Sui XX, Simosa HF, Jain MK, Altieri DC, Conte MS. Regulation of vein graft hyperplasia by survivin, an inhibitor of apoptosis protein. Arterioscler Thromb Vasc Biol. 2005 Oct;25(10):2081-7.
Conte MS, Bandyk DF, Clowes AW, Moneta GL, Namini H, Seely L. Risk factors, medical therapies and perioperative events in limb salvage surgery: observations from the PREVENT III multicenter trial.
J Vasc Surg. 2005 Sep;42(3):456-64; discussion 464-5.
Simosa HF, Wang G, Sui X, Peterson T, Narra V, Altieri DC, Conte MS. Survivin expression is up-regulated in vascular injury and identifies a distinct cellular phenotype. J Vasc Surg. 2005 Apr;41(4):682-90.
Conte MS, Lorenz TJ, Bandyk DF, Clowes AW, Moneta GL, Seely BL. Design and rationale of the PREVENT III clinical trial: edifoligide for the prevention of infrainguinal vein graft failure. Vasc Endovascular Surg. 2005 Jan-Feb;39(1):15-23.
Chew DK, Conte MS, Khalil RA. Matrix metalloproteinase-specific inhibition of Ca2+ entry mechanisms of vascular contraction. J Vasc Surg. 2004 Nov;40(5):1001-10.
Nguyen LL, Conte MS, Menard MT, Gravereaux EC, Chew DK, Donaldson MC, Whittemore AD, Belkin M. Infrainguinal vein bypass graft revision: factors affecting long-term outcome. J Vasc Surg. 2004 Nov;40(5):916-23.
Nguyen LL, Conte MS, Reed AB, Belkin M. Carotid endarterectomy: who is the high-risk patient? Semin Vasc Surg. 2004 Sep;17(3):219-23.
Abbruzzese TA, Havens J, Belkin M, Donaldson MC, Whittemore AD, Liao JK, Conte MS. Statin therapy is associated with improved patency of autogenous infrainguinal bypass grafts. J Vasc Surg. 2004 Jun;39(6):1178-85.
Menard MT, Nguyen LL, Chan RK, Conte MS, Fahy L, Chew DK, Donaldson MC, Mannick JA, Whittemore AD, Belkin M. Thoracovisceral segment aneurysm repair after previous infrarenal abdominal aortic aneurysm surgery. J Vasc Surg. 2004 Jun;39(6):1163-70.
Jacot JG, Abdullah I, Belkin M, Gerhard-Herman M, Gaccione P, Polak JF, Donaldson MC, Whittemore AD, Conte MS. Early adaptation of human lower extremity vein grafts: wall stiffness changes accompany geometric remodeling. J Vasc Surg. 2004 Mar;39(3):547-55.
Mann MJ, Conte MS. Transcription factor decoys for the prevention of vein bypass graft failure. Am J Cardiovasc Drugs. 2003;3(2):79-85.
Reed AB, Conte MS, Donaldson MC, Mannick JA, Whittemore AD, Belkin M. The impact of patient age and aortic size on the results of aortobifemoral bypass grafting. J Vasc Surg. 2003 Jun;37(6):1219-25.
Reed AB, Gaccione P, Belkin M, Donaldson MC, Mannick JA, Whittemore AD, Conte MS. Preoperative risk factors for carotid endarterectomy: defining the patient at high risk. J Vasc Surg. 2003 Jun;37(6):1191-9.
Menard MT, Chew DK, Chan RK, Conte MS, Donaldson MC, Mannick JA, Whittemore AD, Belkin M. Outcome in patients at high risk after open surgical repair of abdominal aortic aneurysm. J Vasc Surg. 2003 Feb;37(2):285-92.
Conte MS, Mann MJ, Simosa HF, Rhynhart KK, Mulligan RC. Genetic interventions for vein bypass graft disease: a review. J Vasc Surg. 2002 Nov;36(5):1040-52. Review.
Lau H, Chew DK, Whittemore AD, Belkin M, Conte MS, Donaldson MC. Transaortic endarterectomy for primary mesenteric revascularization. Vasc Endovascular Surg. 2002 Sep-Oct;36(5):335-41.
Gangadharan SP, Reed AB, Chew DK, Conte MS, Belkin M, Whittemore AD, Donaldson MC. Initial experience with minimally invasive in situ bypass procedure with blind valvulotomy. J Vasc Surg. 2002 Jun;35(6):1100-6.
Chew DK, Owens CD, Belkin M, Donaldson MC, Whittemore AD, Mannick JA, Conte MS. Bypass in the absence of ipsilateral greater saphenous vein: safety and superiority of the contralateral greater saphenous vein. J Vasc Surg. 2002 Jun;35(6):1085-92.
Sun J, Sui X, Bradbury JA, Zeldin DC, Conte MS, Liao JK. Inhibition of vascular smooth muscle cell migration by cytochrome p450 epoxygenase-derived eicosanoids. Circ Res. 2002 May 17;90(9):1020-7.
Back to the top
Send Feedback to: 
