Pharmacology and Toxicology

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Michael E. Widlansky, MD

Associate Professor
Department of Medicine
University of Michigan (1999)
Cardiovascular Pharmacology
Phone: 414 456-6716
Fax: 414-456-6545
mwidlans@mcw.edu

Dr. Widlansky's Faculty Collaboration Database

 


Research Interest

The vascular endothelium, once thought to be a thin layer of quiescent cells present only to allow smooth, laminar blood flow has discovered to be a central regulator of vascular homeostasis. Both traditional and novel cardiovascular risk factors have been shown to induce the endothelium to take on a phenotype characterized by inflammation, pro-thrombotic stimuli, and vasoconstriction. This state of endothelial “dysfunction” has been shown to precede the development of atherosclerosis and portend cardiovascular events in both those with and without clinically evident cardiovascular disease. Endothelium-derived nitric oxide (EDNO) has been shown to be a central paracrine hormone in the maintenance of normal endothelial function, and a central characteristic of endothelial dysfunction is a reduction in bioavailable EDNO. Measuring EDNO bioavailability in larger conduit vessels and in the microvasculature in vivo can be accomplished by multiple modalities, including high-resolution vascular ultrasound and venous plethysmography. We employ these methodologies to investigate the pathophysiological mechanisms underlying the development of endothelial dysfunction in humans with a variety of disease states, including coronary artery disease and diabetes. Currently, we are investigating the role of disturbances in mitochondrial homeostasis in the modulation of vascular endothelial function in humans with Type II Diabetes. Many of our studies are small, clinical studies that apply different interventions to humans to assess their effects on vascular endothelial function, based on basic and animal work suggesting potential mechanisms for such a difference. Current protocols along this line include investigating the differential effects on vascular function of metformin and glipizide in Type II Diabetics. Our human vascular research laboratory has been formed to foster collaboration with investigators from other disciplines interested in the impact of vascular function on disease states relevant to their fields of interest. Current collaborative efforts include work with investigators from disciplines including Orthopedics, Dermatology, Geriatrics, Pediatric Endocrinology, and Pediatric Cardiology.

 


Recent Publications

Widlansky ME, Price DT, Gokce N, Eberhardt RT, Duffy SJ, Holbrook M, Maxwell C, Palmisano J, Keaney JF Jr, Morrow JD, Vita JA. Acute and chronic COX-2 inhibition reverses endothelial dysfunction in patients with hypertension. Hypertension 2003 Sept;42(3):310-5.

Widlansky ME, Biegelsen ES, Hamburg NM, Duffy SJ, Keaney JF, Jr., Vita JA. Coronary endothelial dysfunction is not rapidly reversible with ascorbic acid treatment. Free Radic Biol Med 2004 36(1): 124-31.

Widlansky M, Sesso HD, Rexrode KM, Manson JE, Gaziano JM. Body mass index and total and cardiovascular mortality in men with a history of cardiovascular disease. Arch Int Med 2004;164: 2326-2332.

Widlansky ME, Duffy SJ, Hamburg, NM, Gokce, N, Warden BA, Wiseman S, Keaney JF, Jr., Frei B, Joseph A. Vita JA. Effects of black tea consumption on plasma catechins, markers oxidative stress and inflammation in patients with coronary artery disease. Free Radic Biol Med 2005; 38:499-506.

Widlansky ME, Hamburg NM, Anter E, Holbrook M, Kahn DF, Elliott JG, Keaney JF, Jr, Vita JA. Acute EGCG supplementation reverses endothelial dysfunction in patients with coronary artery disease J Am Coll Nutr 2007; 26(2):95-102.

McMackin CJ, Widlansky ME, Hamburg NM, Huang AL, Weller S, Holbrook M, Gokce N, Hagen TM, Keaney JF, Jr., Vita JA. Effect of combined treatment with alpha lipoic acid and acetyl-L-carnitine on vascular function and blood pressure in coronary artery disease patients. J Clin Hypertens 2007; 9(4): 249-255.

Widlansky ME, Vita JA, Keyes MJ, Larson MG, Hamburg NM, Levy D, Mitchell GF, Osypiuk EW, Vasan RS, Benjamin EJ. Relation of Season and Temperature to Endothelium-Dependent Flow-Mediated Vasodilation in Subjects Without Clinical Evidence of Cardiovascular Disease (From The Framingham Heart Study). Am J Cardiol 2007; 100(3):518-23.

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