Current Research
(Read the January 2010 GSM Scope Newsletter article:
Dr. Mountain Leads HRT Study Funded by American Heart Association
Current Research Studies
The Primary Focal Point of ongoing studies within the Vascular Research Laboratory is the role of hormone replacement therapy in the development of peripheral vascular pathology. Under this primary focus there are 3 ongoing research projects:
Project 1:
Hormone Replacement Therapy: Modulation of Vascular Wall Structure and Remodeling Post-Injury.
Women receiving HRT have more adverse outcomes after vascular reconstruction, including intimal hyperplasia, restenosis, and decreased graft patency, which can ultimately lead to multiple surgical interventions and limb loss. Our hypothesis is that HRT, acting as a proinflammatory modulator during vascular injury, upregulates the matrix metalloproteinase (MMP) pathway and thus contributes to intimal thickening. This hypothesis is being tested in vitro using human VSMCs and in vivo using ovariectomized rodent models of balloon-induced carotid artery injury and end-to-end anastomosis. Our objective is to identify critical rate-limiting steps where pharmacological interventions could prevent or hinder dysfunctional vascular remodeling.
Funding: American Heart Association Scientist Development Grant
PI: Deidra J.H. Mountain, Ph.D. – Department of Surgery, UTGSM
Project 2:
Integrative Experimental/Computational Model of HRT Effects of Vascular Pathology.
Our goal is to quantitatively document the pleiotropic effects of estrogen and progesterone on vascular cell function, develop a computational model of vascular restenosis to aid in the assimilation and integration of experimental in vitro outcomes to understand their biological complexity, and assay targeted inhibition of computationally defined parameters in a rodent model of balloon-induced carotid artery injury for effectiveness in the prevention of pathological vascular remodeling. Future research will include extending and validating the model with clinical data to provide predictive capabilities to accurately predict the outcome of vascular interventions in women receiving HRT.
Funding: Pending – National Institutes of Health, NHLBI R01
PI: Oscar H. Grandas, M.D. – Department of Surgery, UTGSM
Collaborators: Deidra J.H. Mountain, Ph.D. – Department of Surgery, UTGSM
James J. Nutaro, Ph.D. – Division of Computational Sciences and Engineering, Oak Ridge National Laboratories
John Biggerstaff, Ph.D. – Biological Imaging Unit, Center for Environmental Biotechnology, University of Tennessee Knoxville
Project 3:
Effects of Estrogen and Progesterone on Inflammatory Markers, Matrix Metalloproteinase Levels, and Clinical Outcomes in Postmenopausal Females after Vascular Reconstruction: A Prospective Study.
Understanding the hormone-regulated modifications to the balance MMPs is critical to the development of specific therapeutic options for patients with vascular disease. Women with and without HRT, undergoing open infrainguinal revascularizations, are being followed prospectively 12 months for primary graft patency. Preoperative and postoperative determinations of serum inflammatory markers and MMPs are being measured, and levels of inflammatory markers, MMP enzymes, risk factors, and procedure specifics are then correlated to patency and clinical outcomes. If evidence proves that increased inflammatory response and MMP activity is associated with decreased graft patency in women exposed to HRT, targeted interventions to this end could dramatically improve long-term outcomes.
Funding: Society of Vascular Surgery Clinical Research Seed Grant
PI: Oscar H. Grandas, M.D. – Department of Surgery, UTGSM
Collaborators: Deidra J.H. Mountain, Ph.D. – Department of Surgery, UTGSM
David C. Cassada, M.D.
Michael B. Freeman, M.D.
Mitchell H. Goldman, M.D.
There are a number of other ongoing studies within the Vascular Research Laboratory. These Secondary Focal Points of interest include:
Creation of an anastomotic model of intimal hyperplasia to establish equivalence with an accepted balloon angioplasty model. The established technique currently accepted for examining intimal hyperplasia development experimentally in animal models is balloon-induced injury of the carotid artery. However, hyperplasia development in vascular grafting is in response to a much different vascular injury, caused during stitching the vessel and graft ends together, a process called anastomosis. Our aim is to create a microsurgical anastomotic model of intimal hyperplasia of the carotid artery and to establish its equivalence to the balloon-injury model as an accepted experimental design. Using identical conditions and time points we are examining hyperplasia development over time in response to vascular anastomosis compared to development over time in response to balloon angioplasty.
Funding: Physicians’ Medical Education and Research Foundation
PI: Victor Krylov, M.D., Ph.D. – Department of Surgery, UTGSM Oscar H. Grandas, M.D. – Department of Surgery, UTGSM
Deidra J.H. Mountain, Ph.D. - Department of Surgery, UTGSM
Polymeric Venous Valve.
Chronic venous insufficiency (CVI), a condition in which veins located in the lower extremities weaken and lose their ability to effectively pump blood back to the heart. When these vein valves become defective, blood pools near the feet, causing leg swelling and expansion of the affected vein, and destroying the venous valves beyond repair by any surgical procedure. Currently, there is no technology to restore venous valves and cure CVI. We are collaborating to design a biocompatible synthetic vein valve. Our design is a fully polymeric device and therefore has optimal blood compatibility, and our design is based on the use of a dip coating apparatus since it allows for very accurate control of the layer thickness. Fluid modeling is being used to analyze the valve’s opening and closing mechanism in order to optimize the physiological design of the device. We are specifically exploring different surface grafting and texturing techniques to create a surface that will meet the requirements of venous blood contact. Finally, animal testing of the device will be implemented during the final phases of development.
Funding: Physicians’ Medical Education and Research Foundation
PI: Mitchell H. Goldman, M.D. – Department of Surgery, UTGSM
Collaborators: Victor Krylov, M.D., Ph.D. – Department of Surgery, UTGSM
Deidra J.H. Mountain, Ph.D. - Department of Surgery, UTGSM
Roberto Benson, Ph.D. - Department of Polymer Engineering, UTK
Chris Stevens, Ph.D.
Microsurgical Teaching Course.
The Vascular Research Laboratory organizes and faculty within the laboratory administer a microsurgical teaching course offered to 4th/5th year residents and others who want to perfect their skills in this particular surgical technique. This course is designed for fellows and residents at UTGSM, but is offered to interested staff members of the Department of Surgery as well. The aim of this course is to teach students surgical techniques using optical magnification above 3X and focuses on surgical manipulations of small caliber vessels (1 mm and less). Surgeons of surgical specialties (trauma, plastics, urology, OB/GYN, neurosurgery) can be given detailed training of typical microsurgical interventions in their corresponding domains. Beginning sessions include a lecture series on microsurgical technique and hands-on sessions taught using synthetic materials such as latex thin-walled synthetic tubing and a synthetic rat model (PVC-rat). After gaining the initial experience of working with the operating microscope, the microsurgical instruments, and the synthetic material, the advanced sessions are carried out using material of biological origin (blood vessels harvested from livestock) and a live rat model.
The University of Tennessee Graduate School of Medicine
Vascular Research Laboratory
Department of Surgery
1924 Alcoa Highway, Box U-11
Knoxville, TN 37920
Phone: 865-305-6126 or 865-305-9160
Fax: 865-305-6048