Vascular Research Program at the VA Puget Sound

Wijelath_Sobel3
Errol S. Wijelath, PhD
Principal Investigator
Research Associate Professor
Division of Vascular Surgery
Michael Sobel, MD, FACS
Principal Investigator
Professor of Surgery
Division of Vascular Surgery
Mission

Our research program is focused on the following goals:

  • Understanding how inflammation and genetics influence the vascular healing response.
  • Developing new therapies to improve the success and longevity of vascular surgical interventions.

Our body’s inflammatory reactions, as well as our genetic makeup, profoundly influence our healing response to injury. Vascular interventions routinely injure the blood vessels (whether by stenting, endarterectomy or bypass grafting). Although many patients go on to heal normally, up to 30% suffer from a deranged form of healing that leads to narrowing of the vascular reconstruction, stenosis, thrombosis, and failure. Little is known about the biologic underpinnings of this dysfunctional healing response, or why it affects some patients but not others.

Figure 1. Kaplan-Meier Survival Analysis of Primary Graft Patency. The differences in graft survival were significant (p=.0085 log-rank test). The numbers above and below the graph lines indicate the number of subjects at risk at each interval.

Figure 1. Kaplan-Meier Survival Analysis of Primary Graft Patency. The differences in graft survival were significant (p=.0085 log-rank test). The numbers above and below the graph lines indicate the number of subjects at risk at each interval.

Collaborators

Zhau Ming Dong, MD, PhD, Associate Professor, UW Department of Pathology
Thomas Hatsukami, MD, Professor, UW Department of Surgery
Grant O’Keefe, MD, Professor, UW Department of Surgery
Michael Rosenfeld, PhD, Professor, UW Departments of Pathology and Environmental and Occupational Health Sciences

Funding

Veterans Affairs R&D (PI: Sobel)
Preventing Vein Graft Stenosis in Peripheral Vascular Surgery
This is a longitudinal study of patients undergoing leg bypass for ischemia, in which we will correlate their perioperative thrombo-inflammatory responses with clinical outcomes, with a focus on graft stenosis and failure.

National Institutes of Health (NIH)/National Heart, Lung and Blood Institute (NHLBI) (Co-PIs: Sobel, Clowes)
Mechanisms of arterial graft healing
This project explores the cellular basis for vein graft stenosis, focusing on the genetic and biological determinants that control

Veterans Affairs R&D (PI: Wijelath)
Role of the Inflammatory Cytokine Oncostatin-M in Promoting Atherosclerosis.
The objective of this project is to understand how the JAK-STAT pathway regulates smooth muscle cell phenotype at a molecular and cellular level.

Significant Publications
  1. Cabbage S, Ieronimakis N, Preusch M, Lee A, Ricks J, Janebodin K, Hays A, Wijelath ES, Reyes M, Campbell LA, Rosenfeld ME: Chlamydia Pneumoniae Infection of Lungs and Macrophages Indirectly Stimulates the Phenotypic Conversion of Smooth Muscle Cells and Mesenchymal Stem Cells: Potential Roles in Vascular Calcification and Fibrosis. Pathog Dis. 2014 May 15. doi: 10.1111/2049-632X.12185. [Epub ahead of print]
  2. Kirchmer MN, Franco A, Albasanz-Puig A, Murray J, Yagi M, Gao L, Dong ZM, Wijelath ES: Modulation of vascular smooth muscle cell phenotype by STAT-1 and STAT-3. Atherosclerosis. 2014; 234(1):169-75.
  3. Conte MS, Owens CD, Belkin M, Creager MA, Edwards KL, Gasper WJ, Kenagy RD, LeBoeuf RC, Sobel M, Clowes AW. A single nucleotide polymorphism in the p27 Kip1 gene is associated with primary patency of lower extremity vein bypass grafts. J Vasc Surg. 2013;57:1179-85. PMID: 23312942. PMC3644510.
  4. Sobel M, Moreno KI, Yagi M, Kohler TR, Tang GL, Clowes AW, Zhou XH, Eugenio E. Low levels of a natural IgM antibody are associated with vein graft stenosis and failure. J Vasc Surg. 2013;58:997-1005. PMID: 23856610. PMC pending.
  5. Yagi M, Murray J, Strand K, Blystone S, Interlandi G, Suda Y, Sobel M. Heparin modulates the conformation and signaling of platelet integrin αIIbβ3. Thromb Res. 2012;129:743-9. PMID:22197178.
  6. Moreno K, Murray-Wijelath J, Yagi M, Kohler T, Hatsukami T, Clowes A, Sobel M. Circulating inflammatory cells are associated with vein graft stenosis. J Vasc Surg. 2011;54:1124-30. PMID: 21906902.
  7. Stenzel D, Lundkvist A, Sauvaget D, Busse MN, Graupera M, van der Flier A, Wijelath ES, Murray J, Sobel M, Takahashi S, Fässler R, Yamaguchi Y, Gutmann DH, Hynes RO, Gerhardt H. Integrin-dependent and independent functions of astrocytic fibronectin in retinal angiogenesis. Development. 2011;138:4451-63. PMID: 21880786.
  8. Albasanz-Puig A, Murray J, Preusch M, Coan D, Namekata M, Patel Y, Dong ZM, Rosenfeld ME, Wijelath ES: Oncostatin M is expressed in atherosclerotic lesions: A role for Oncostatin M in the pathogenesis of atherosclerosis. Atherosclerosis. 2011;16(2): 292-298.
Modified March 11, 2016 – MDH