Type 2 Diabetes has become an epidemic in the United States. Cardiovascular disease is the most common cause of death in this population and is two to four fold higher than the general population. This increased risk is at least partially attributable to the high prevalence of the metabolic syndrome with its multiple coronary heart disease risk factors including central obesity, hypertension, glucose intolerance, chronic inflammation, and dyslipidemia. However, recent trials have demonstrated that traditional risk factors alone are not completely predictive of disease burden particularly early in the disease process prior to the development of flow-limiting coronary stenoses. Diagnosis and prevention of cardiovascular disease development has, thus, been elusive in this high risk population. It is not entirely clear which factors, known or novel, contribute the most in very early disease and which therapies may be most beneficial.
Drs. Coleen McNamara and Angela Taylor have teamed with Dr. Lynn Hedrick on a multi-year NIH Funded Program Project Grant (PPG) titled "Immune Cells in Atherosclerosis and Vascular Disease".
Dr. McNamara's project titled, "B-1A Lymphocytes in Atherosclerosis" hypothesizes that Id3 in B cells is necessary for B-la cell atheroprotection through promoting B-la cell cycle progression and self-renewal resulting in increased levels of atheroprotective natural antibodies such as E06. This hypothesis and the molecular and cellular mechanisms mediating these effects will be studied in aims 1 and 2. Moreover, they will translate these novel findings in mice into testable hypotheses in humans with type 2 diabetes (T2DM). Through collaborations with projects 1 and 2 and our human core, we are uniquely poised to test these innovative hypotheses to identify molecular mechanisms regulating atheroprotective B cells in mice and humans, potentially leading to identification of novel biomarkers and novel strategies to bolster innate immune protection against atherosclerosis.
Dr. Taylor, along with Dr. McNamara, are managing the Human Phenotyping and Immune Cell Core. The function of Core is to provide human and immune cell phenotyping for each project that will be critical to the translation of mechanistic findings into the human model.
The effects of immune cell variations on atherosclerosis in humans represents a poorly understood area of atherogenesis and possible atheroprotection. The goal of the Human Phenotyping and Immune Cell Core (Core B) is to provide the resources necessary for translation of novel immune mechanisms of atherosclerosis that are well defined in murine models into the human model.
Bourque JM, Schietinger BJ, Kennedy JL, Pearce EA, Christopher JM, Taylor AM, McNamara CA, Kramer CM. Usefulness of cardiovascular magnetic resonance imaging of the superficial femoral artery for screening patients with diabetes mellitus for atherosclerosis. Am J Cardiol. 2012 Jul 1;110(1):50-6. doi: 10.1016/j.amjcard.2012.02.048. Epub 2012 Mar 27.
Keeley EC, Moorman JR, Liu L, Gimple LW, Lipson LC, Ragosta M, Taylor AM, Lake DE, Burdick MD, Mehrad B, Strieter RM. Plasma chemokine levels are associated with the presence and extent of angiographic coronary collaterals in chronic ischemic heart disease. PLoS One. 2011;6(6):e21174. doi: 10.1371/journal.pone.0021174. Epub 2011 Jun 22.
Enkiri SA, Taylor AM, Keeley EC, Lipson LC, Gimple LW, Ragosta M. Coronary angiography is a better predictor of mortality than noninvasive testing in patients evaluated for renal transplantation. Catheter Cardiovasc Interv. 2010 Nov 15;76(6):795-801. doi: 10.1002/ccd.22656.
Jones DG, Taylor AM, Enkiri SA, Lobo P, Brayman KL, Keeley EC, Lipson LC, Gimple LW, Ragosta M. Extent and severity of coronary disease and mortality in patients with end-stage renal failure evaluated for renal transplantation. Am J Transplant. 2009 Aug;9(8):1846-52. doi: 10.1111/j.1600-6143.2009.02703.x. Epub 2009 Jun 16.
Winchester DE, Ragosta M, Taylor AM. Concurrence of angiographic coronary artery disease in patients with apical ballooning syndrome (tako-tsubo cardiomyopathy). Catheter Cardiovasc Interv. 2008 Nov 1;72(5):612-6. doi:10.1002/ccd.21738. PubMed PMID: 18798323.
Taylor AM. Cardiometabolic risk management in type 2 diabetes and obesity. Curr Diab Rep. 2008 Oct;8(5):345-52.
Taylor AM, Li F, Thimmalapura P, Gerrity RG, Sarembock IJ, Forrest S, Rutherford S, McNamara CA. Hyperlipemia and oxidation of LDL induce vascular smooth muscle cell growth: an effect mediated by the HLH factor Id3. J Vasc Res. 2006;43(2):123-30. Epub 2005 Dec 7.
Taylor AM, Hanchett R, Natarajan R, Hedrick CC, Forrest S, Nadler JL, McNamara CA. The effects of leukocyte-type 12/15-lipoxygenase on Id3-mediated vascular smooth muscle cell growth. Arterioscler Thromb Vasc Biol. 2005 Oct;25(10):2069-74. Epub 2005 Jul 21.
Forrest ST, Taylor AM, Sarembock IJ, Perlegas D, McNamara CA. Phosphorylation regulates Id3 function in vascular smooth muscle cells. Circ Res. 2004 Sep 17;95(6):557-9. Epub 2004 Aug 19.
Cerosaletti KM, Lange E, Stringham HM, Weemaes CM, Smeets D, Solder B, Belohradsky BH, Taylor AM, Karnes P, Elliott A, Komatsu K, Gatti RA, Boehnke M, Concannon P. Fine localization of the Nijmegen breakage syndrome gene to 8q21: evidence for a common founder haplotype. Am J Hum Genet. 1998 Jul;63(1):125-34.