Timothy R. Nurkiewicz, Ph.D.
	Assistant Professor of Physiology and Pharmacology   Graduate Training: West Virginia University Fellowship: Texas A&M University
	Office: 3140-HSN Lab: 3138-HSN PO Box 9105 Morgantown, WV 26506	Email: tnurkiewicz@hsc.wvu.edu Phone: 304-293-7328 Fax: 304-293-5513

Research Interests:

Ambient air pollution is a nationwide problem, particularly in states such as West Virginia where industry, population and general growth are rapidly rising. Particulate matter (PM) is one of the six principle air pollutants nationally tracked by the Environmental Protection Agency. Acute exposure to PM increases morbidity and mortality, as evidenced by the increased occurrence of cardiovascular dysfunction on high pollution days. Populations such as the young, elderly and ill are at greater risk when exposed to PM. While the association between untoward health effects and PM exposureis now known, the fundamental mechanisms by which PM elicits cardiovascular dysfunction remain largely unknown. Only recently have scientists begun to explore the possibility that the systemic effects of PM may be more important than those traditionally investigated in the lung.

Figure 1: Fluorescent images after dihydroethidine exposure indicating oxidative stress in the arteriolar wall. Pictures are from the rat spinotrapezius muscle. Left picture, normal arcade bridge arteriole. Right picture, arcade bridge arteriole in a rat 24 hours post PM exposure (2 mg).	Figure 2: Transillumination of the spinotrapezius muscle displaying leukocyte adhesion. Top, normal venule. Bottom, venule in rat treated with PM. Rolling and adhering leukocytes are the white “spots” in the venular lumen.

The ability of the microcirculation to maintain blood flow in any tissue is dependent on many factors including: 1) endothelial interaction with smooth muscle, and 2) chemical communication between arterioles and venules. My laboratory has recently discovered that endothelium-dependent arteriolar dilation is profoundly impaired after PM exposure. This dysfunction is associated with endothelium-derived nitric oxide, as well as other endothelial factors that influence arteriolar smooth muscle tone.

To better understand why arteriolar dilation is impaired after PM exposure, we have used fluorescent markers to characterize microvascular oxidative stress. Oxidative stress in the microcirculation is capable of disrupting endothelial-smooth muscle cell interactions. Figure 1 indicates that oxidative stress is prominent in the arteriolar wall after PM exposure.

We have also explored the potential source of oxidative stress after PM exposure. Exposure to toxic stimuli initiates a complex systemic inflammatory response. One characteristic of an inflammatory response is increased leukocyte adhesion and rolling in the microcirculation. Leukocytes generate oxidative stress liberally as part of a normal immune response. Figure 2 shows that microvascular leukocyte adhesion and rolling is significantly increased after PM exposure.

The goal of our research is to identify the adverse effects of PM exposure on microvascular function, and determine the mechanisms that cause these potentially lethal effects. A second goal is to characterize why large “at risk” populations are more prone to be victims of PM exposure. Additional images and video from our studies can be found in the Media Library.

Selected References:

1. Nurkiewicz, T.R., D.W. Porter, A.F. Hubbs, J.L. Cumpston, B.T. Chen, D.G. Frazer, and V. Castranova. Nanoparticle Inhalation Augments Particle-Dependent Systemic Microvascular Dysfunction. Particle and Fibre Toxicology. 5:1, 2008.  PDF
2. Prisby, R.D., J. Muller-Delp, M.D. Delp and T.R. Nurkiewicz. Age, Gender and Hormonal Status Modulate the Vascular Toxicity of the Diesel Exhaust Extract Phenanthraquinone. Journal of Toxicology and Environmental Health. Part A, 71:464-470, 2008.  PDF
3. Nurkiewicz T.R., and M.A. Boegehold. High salt intake reduces endothelium-dependent dilation of mouse arterioles via superoxide anion generated from nitric oxide synthase. Am J Physiol Regul Integr Comp Physiol. 2007 Apr;292(4):R1550-6. PDF
4. Nurkiewicz, T.R. ,D. W. Porter, M. Barger, L. Millecchia, K.M.K. Rao, P.J. Marvar, A.F. Hubbs, V. Castranova, and M.A. Boegehold. Systemic Microvascular Dysfunction and Inflammation After Pulmonary Particulate Matter Exposure . Environmental Health Perspectives. 114:412-419, 2006. PDF
5. Nurkiewicz, T. R. , D.W. Porter, M. Barger, V. Castranova, and M.A. Boegehold. Particulate Matter Exposure Impairs Systemic Microvascular Endothelium-Dependent Dilation. Environmental Health Perspectives. 112:1299-1306, 2004. PDF
6. Nurkiewicz, T.R. and M.A. Boegehold. Calcium-independent release of endothelial nitric oxide in the arteriolar network: onset during rapid juvenile growth. Microcirculation. 11: 453-462, 2004. PDF
7. Davis M.J., X. Wu, T.R. Nurkiewicz , J. Kawasaki, P. Gui, M.A. Hill, and E. Wilson. Regulation of ion channels by integrins. Cell Biochemistry and Biophysics . 36(1):41-66, 2002. PDF
8. Davis , M.J., Wu, X., Nurkiewicz, T.R. , Kawasaki , J., Davis, G.E., Hill, M.A., and Meininger, G.A. Integrins and mechanotransduction of the vascular myogenic response. Am. J. Physiol. Heart Circ. Physiol. 280: H1427-H1433, 2001. PDF
9. Nurkiewicz, T.R. and M.A. Boegehold. Reinforcement of arteriolar myogenic activity by endogenous angiotensin II: susceptibility to dietary salt. Am. J. Physiol. Heart Circ. Physiol. 279: H269-H278, 2000. PDF

Lab Personnel:

Carroll McBride - Research Assistant II
Kim Wix - Research Assistant II
Katrina Sites - Graduate Student