Vascular Research

 

Our Division is committed to the development and integration of innovations in vascular research and technology. To that end, we are heavily involved in three major types of research: basic science, clinical trials, and clinical outcomes research.

 

Basic Science Research

The Vascular Research Laboratory, in its current form, was established by Dr. Louis Messina in 2006. He has enjoyed continuous extrinsic NIH funding for twenty years.  His current research program has two major areas of focus. One is on NIH-funded work to indentify the cellular and molecular mechanisms that regulate collateral artery enlargement. His lab has shown that collateral artery enlargement is dependent on both hematopoietic and mesenchymal stem cells rather than as traditionally thought local tissue response by terminal differentiated cells in an ischemic environment. They have shown that oxidant stress by cardiovascular risk factors such as type-2 diabetes and hypercholesterolemia induce epigenetic changes that decreases the number and phenotype of terminally differentiated cells central to collateral artery enlargement such as monocytes. These epigenetic changes induce a higher proportion of pro-inflammatory monocytes than pro-angiogenic monocytes. These findings are generalizable.

The second area of focus is how these effects of oxidant stress on hematopoietic and mesenchymal stem cells affect immunosurveillance against colorectal cancer and wound healing. The overarching result of these studies is that oxidant stress of stem cells is a critical regulator of innate immunity and inflammation. Three NIH RO-1 grants have been submitted this year.

Recent Publications

Uncoupling Protein 2 Impacts Endothelial Phenotype via p53-Mediated Control of Mitochondrial Dynamics. Shimasaki Y, Pan N, Messina LM, Li C, Chen K, Liu L, Cooper MP, Vita JA, Keaney JF. Circ Res. 2013 Jul 2.    PMID: 23819990

Mesenchymal stem cells as a treatment for peripheral arterial disease: current status and potential impact of type II diabetes on their therapeutic efficacy. Yan J, Tie G, Xu TY, Cecchini K, Messina LM.  Stem Cell Rev. 2013 Jun;9(3):360-72. doi: 10.1007/s12015-013-9433-8.  PMID: 23475434

Type 2 diabetes restricts multipotency of mesenchymal stem cells and impairs their capacity to augment postischemic neovascularization in db/db mice. Yan J, Tie G, Wang S, Messina KE, DiDato S, Guo S, Messina LM.  J Am Heart Assoc. 2012 Dec;1(6):e002238. doi: 10.1161/JAHA.112.002238. Epub 2012 Dec 19.  PMID: 23316315

Tetrahydrobiopterin, L-arginine and vitamin C act synergistically to decrease oxidant stress and increase nitric oxide that increases blood flow recovery after hindlimb ischemia in the rat. Yan J, Tie G, Messina LM.  Mol Med. 2012 Oct 24;18:1221-30. doi: 10.2119/molmed.2011.00103.revised.  PMID: 23212846

 

Clinical Trials

In collaboration with the Department of Surgery’s Center for Clinical Research and Trials, we are pleased to participate in a number of clinical trials. This allows us to offer cutting edge therapies for a number of vascular conditions including complex aortic pathology, nonreconstructible critical limb ischemia, and hemodialysis access surgery for end-stage renal disease. Sponsorship of these trials is diverse, including the investigator, the National Institutes of Health, the Society for Vascular Surgery, and a number of industry leaders.

 Clinical Trials Nov 2014

Clinical Trials key

 

 

Clinical Outcomes Research

 Our group has diverse areas of interest in clinical research, ranging from predictors of sac enlargement after endovascular aneurysm repair, national and regional variation in diagnosis and management of carotid disease, and risk stratification for lower extremity bypass and abdominal aortic aneurysm repair, to research on surgical education and training paradigms. Below is a list of recent peer-reviewed publications and descriptions of specific faculty research interests.

 

Faculty

 Francesco A. Aiello, MD

 My research program has focused on the evaluation of the accuracy of the two main registries of vascular surgery procedures, the Vascular Surgery Quality Initiative and NISQP. With colleagues from QHS including Drs. Amy Rosen and Bruce Barton, we have to our surprise that neither registry provides an accurate measure of the outcome of vascular surgery procedures. Such registries are fundamental to determining the quality and effectiveness of such procedures. This work has been accepted for presentation at the New England Vascular Society of Vascular Surgery in September and we plan submission of a manuscript to the Journal of Vascular Surgery.  In ongoing work, we analyze this data to refine this analysis to shed more light on the sources of this inaccuracy. We hope to transition this work towards preliminary data for a K award.

 

Louis M. Messina, MD

My current research program has two major areas of focus. One is on NIH-funded work to indentify the cellular and molecular mechanisms that regulate collateral artery enlargement. We have shown that collateral artery enlargement is dependent on both hematopoietic and mesenchymal stem cells rather than as traditionally thought local tissue response by terminal differentiated cells in an ischemic environment. We have shown that oxidant stress by cardiovascular risk factors such as type-2 diabetes and hypercholesterolemia induce epigenetic changes that decreases the number and phenotype of terminally differentiated cells central to collateral artery enlargement such as monocytes. These epigenetic changes induce a higher proportion of pro-inflammatory monocytes than pro-angiogenic monocytes. These findings are generalizable. The second area of focus is how these effects of oxidant stress on hematopoietic and mesenchymal stem cells affect immunosurveillance against colorectal cancer and wound healing. The overarching result of these studies is that oxidant stress of stem cells is a critical regulator of innate immunity and inflammation. We plan to submit three NIH RO-1 grants this year.

 

William P. Robinson, III, MD

 My research has focused on two principle areas. The outcomes of vascular interventions are one focus, with a particular interest in the use of risk prediction in the assessment of outcomes and the use of appropriate risk adjustment in the development of quality metrics.  This has led to our interest in developing accurate risk prediction scores for ruptured abdominal aortic aneurysm (AAA) repair which was published in the Journal of Vascular Surgery. In addition, utilizing validated risk adjustment, we have performed the largest published comparisons of both the short-term and long-term outcomes after EVAR vs. Open Repair of Ruptured AAA. These analyses have been presented at two national meetings and submitted to the Journal of Vascular Surgery. Together with colleagues in QHS, we have also performed an extensive analysis of the AHRQ quality measure for AAA repair (IQI# 11, In-Hospital Mortality Rate after AAA Repair) and have shown it to be inaccurate. This work has also been presented nationally and published in the Journal of Vascular Surgery.               The second area is the development of simulation curriculum, models, and assessment tools and the investigation of the impact of simulation training on vascular skill acquisition.  To this end, I developed a simulator of open AAA repair and have published the results of a prospective study of the effectiveness of different ways in which to teach residents utilizing this AAA simulator. Our group has also published a prospective analysis on the effectiveness of vascular skills courses of various durations on the vascular surgical skills of junior trainees. Finally, I initiated and am Director of the UMass Vascular Skills and Simulation Course (UVASC), a comprehensive open and endovascular simulation course attended by vascular trainees from across the U.S. An analysis of the effectiveness and impact of such a simulation course is forthcoming.

 

Andres Schanzer, MD

I have continued to pursue two major areas of research: the investigation of vascular surgery patient characteristics that predict major clinical outcomes using risk prediction modeling, and the evaluation of new endovascular technologies for the treatment of complex aortic pathology.  I also continue to enjoy mentoring our vascular surgery residents on a number of clinical outcomes research projects with the goal of ensuring that each trainee is involved with the design, implementation, presentation, and publication of a clinical study.  My primary focus at this time is running our FDA approved physician sponsored investigational device exemption trial evaluating the safety and efficacy of physician modified endografts for the minimally invasive treatment of juxtarenal, pararenal, and thoracoabdominal aortic aneurysms (CARPE study).  We are currently enrolling patients and have been receiving a growing number of regional referrals to the trial. Our preliminary experience was presented at this year’s annual meeting of the Society for Vascular Surgery and is in press at the Journal of Vascular Surgery.

 

 

Jessica P. Simons, MD MPH

The emphasis of my research is on methods of assessment of outcomes and quality for vascular disease. Specific current efforts are focused on lower extremity peripheral arterial disease. I am using national data to assess current risk stratification models for predicting amputation-free survival, as well as deriving a novel model with enhanced performance.  Ultimately, this work will inform a larger research project that explores the efficacy of current methods of preoperative counseling, and seeks to create an individualized patient-specific preoperative guide. This guide will not only provide individualized risk estimates for common outcomes after lower extremity bypass but will also ensure patient-centered communication occurs, which has been identified by the Institute of Medicine as a key component of patient-centered care and a key initiative for the improvement of national healthcare.