Coleen A. McNamara

Primary Appointment

  • Professor, Medicine- Cardiovascular Medicine


Research Interest(s)

Atherosclerosis, Obesity, Diabetes

Research Description

In recent years, obesity and diabetes have reached epidemic proportions. These diseases have many health consequences including stroke, heart attack and peripheral vascular disease. Common to all of these is atherosclerosis, which is the process by which lipids, cells and fibrous elements accumulate within the walls of arteries. Coordinated gene expression is essential to maintain normal vascular tissue structure and function and many transcription factors regulate these processes. Our lab has recently identified the transcription factor Id3 as a major regulator of atherosclerosis and obesity. Our research currently focuses on these two areas, each of which includes several exciting projects: Atherosclerosis: Project 1: Id3 regulation of immune cell responses in atherosclerosis. A variety of immune cells influence the development of atherosclerosis, including macrophages, T cells and B cells. While the role of B lymphocytes in atherosclerosis is understudied, they are generally thought to play a protective role. Using animal models, our lab has demonstrated that Id3 regulates the homing of B cells to the vasculature and that the loss of Id3 results in increased plaque formation. In ongoing research, we are utilizing different molecular imaging modalities to further explore and quantify the trafficking of radio-labeled cells to the vessel wall using intravital confocal microscopy, microSPECT/CT, and real-time imaging of cellular trafficking using a gamma camera. In addition, we hope to further elucidate the mechanism by which Id3 affects the function of these cells in disease. Project 2: Id3 regulation of matrix formation and vascular remodeling. Restenosis after stent deployment in atherosclerotic arteries is characterized by neointimal formation. Vascular smooth muscle cell migration, growth and matrix production are critical processes in atherosclerosis and restenosis. Our lab has previously demonstrated that Id3 is involved in vascular smooth muscle cell growth. Our data also indicates that Id3 plays a role in regulating extracellular matrix formation and matrix metalloproteinases, the enzymes that remodel matrix and facilitate cell migration. Using transgenic and knockout mice, and molecular and cellular biology techniques, our lab is currently investigating how Id3 regulates matrix protein production, and its remodeling by select matrix metalloproteinase enzymes. Project 3: Id3 SNPs are associated with atherosclerosis. Through strong collaborations with the UVA Center for Public Health Genomics, our lab is studying several SNPs that have been associated with various markers of atherosclerosis in diabetic and atherosclerotic populations. In ongoing research, we are determining the mechanism by which these SNPs alter Id3 function in order to understand how they might influence disease progression. Obesity: Project 4: Id3 regulation of adipose distribution and adipocyte function. Studies from our lab have shown an important role for Id3 in the regulation of visceral adiposity in the mouse model. We have also demonstrated the role of Id3 in the transcriptional regulation of adiponectin (an anti-inflammatory cytokine produced by adipocytes). Further studies are underway to investigate the role of Id3 in the proliferation and differentiation of adipocytes and the role of Id3 in adipocyte function.

Selected Publications

  • Manichaikul A, Rich S, Perry H, Yeboah J, Law M, Davis M, Parker M, Ragosta M, Connelly J, McNamara C, Taylor A. A functionally significant polymorphism in ID3 is associated with human coronary pathology. PloS one. 2014;9(3): e90222. PMID: 24603695 | PMCID: PMC3946163
  • Perry H, Oldham S, Fahl S, Que X, Gonen A, Harmon D, Tsimikas S, Witztum J, Bender T, McNamara C. Helix-loop-helix factor inhibitor of differentiation 3 regulates interleukin-5 expression and B-1a B cell proliferation. Arteriosclerosis, thrombosis, and vascular biology. 2013;33(12): 2771-9. PMID: 24115031 | PMCID: PMC4003558
  • Bourque J, Schietinger B, Kennedy J, Pearce E, Christopher J, Taylor A, McNamara C, Kramer C. Usefulness of cardiovascular magnetic resonance imaging of the superficial femoral artery for screening patients with diabetes mellitus for atherosclerosis. The American journal of cardiology. 2012;110(1): 50-6. PMID: 22459304 | PMCID: PMC3377855
  • Campbell K, Lipinski M, Doran A, Skaflen M, Fuster V, McNamara C. Lymphocytes and the adventitial immune response in atherosclerosis. Circulation research. 2012;110(6): 889-900. PMID: 22427326 | PMCID: PMC3373006
  • Lipinski M, Campbell K, Duong S, Welch T, Garmey J, Doran A, Skaflen M, Oldham S, Kelly K, McNamara C. Loss of Id3 increases VCAM-1 expression, macrophage accumulation, and atherogenesis in Ldlr-/- mice. Arteriosclerosis, thrombosis, and vascular biology. 2012;32(12): 2855-61. PMID: 23042815 | PMCID: PMC3509414
  • Perry H, Bender T, McNamara C. B cell subsets in atherosclerosis. Frontiers in immunology. 2012;3 373. PMID: 23248624 | PMCID: PMC3518786
  • Perry H, McNamara C. Refining the role of B cells in atherosclerosis. Arteriosclerosis, thrombosis, and vascular biology. 2012;32(7): 1548-9. PMID: 22699274
  • Cutchins A, Harmon D, Kirby J, Doran A, Oldham S, Skaflen M, Klibanov A, Meller N, Keller S, Garmey J, McNamara C. Inhibitor of differentiation-3 mediates high fat diet-induced visceral fat expansion. Arteriosclerosis, thrombosis, and vascular biology. 2011;32(2): 317-24. PMID: 22075252 | PMCID: PMC3262109
  • Doran A, Lipinski M, Oldham S, Garmey J, Campbell K, Skaflen M, Cutchins A, Lee D, Glover D, Kelly K, Galkina E, Ley K, Witztum J, Tsimikas S, Bender T, McNamara C. B-cell aortic homing and atheroprotection depend on Id3. Circulation research. 2011;110(1): e1-12. PMID: 22034493 | PMCID: PMC3253259
  • Deliri H, Meller N, Kadakkal A, Malhotra R, Brewster J, Doran A, Pei H, Oldham S, Skaflen M, Garmey J, McNamara C. Increased 12/15-lipoxygenase enhances cell growth, fibronectin deposition, and neointimal formation in response to carotid injury. Arteriosclerosis, thrombosis, and vascular biology. 2010;31(1): 110-6. PMID: 20947825
  • Doran A, Lehtinen A, Meller N, Lipinski M, Slayton R, Oldham S, Skaflen M, Yeboah J, Rich S, Bowden D, McNamara C. Id3 is a novel atheroprotective factor containing a functionally significant single-nucleotide polymorphism associated with intima-media thickness in humans. Circulation research. 2010;106(7): 1303-11. PMID: 20185798 | PMCID: PMC2860382
  • Lipinski M, Perry H, Doran A, Oldham S, McNamara C. Comment on "Conventional B2 B cell depletion ameliorates whereas its adoptive transfer aggravates atherosclerosis". Journal of immunology (Baltimore, Md. : 1950). 2010;186(1): 4; author reply 6. PMID: 21172871