Phone: 706-721-9103
Fax: 706-721-7299

Email: aergul@mcg.edu
Office: CA 2094

The overall goal of my laboratory is to better understand the mechanistic basis of vascular dysfunction, in order to identify new targets and develop new strategies to prevent cardiovascular disease in diabetes. An important long-term goal in the approach to prevent complications associated with diabetes is to understand the mechanisms that regulate the structure of vessel wall; a process termed "vascular remodeling." We are particularly interested in the effects of diabetes on cerebrovascular function and structure because diabetes increases the risk of stroke as well as worsening stroke outcome. Thus, we focus our efforts to identify causal factors and mechanisms that contribute to remodeling of the cerebrovasculature in diabetes.

We found that endothelin (ET) system is altered in a way to promote increased vasoconstriction in patients with diabetes. Furthermore, we found that ET-1 increases activity of matrix metalloproteinases (MMP), a family of enzymes that are responsible for the dynamic regulation of extracellular matrix. Building upon the results we obtained with human tissue, we now use integration of animal models of Type 2 diabetes with cellular and biochemical approaches to define the role of ET-1, ET receptors and diabetes on vascular structure with particular emphasis on MMP regulation.

Vasculoprotectin and Endothelin B Receptors in Diabetes: This project seeks to determine the interaction between the endothelin (ET) system and matrix metalloproteinases (MMP) in regulation of vascular function and structure in peripheral and cerebral vasculature.

Effect Of Diabetes On Ischemic Brain Injury: This project focuses on the effects of diabetes-induced changes in the cerebrovascular structure on increased risk of stroke as well as mechanisms of worsened stroke outcome in diabetes.

Microvascular Remodeling And Vascular Complications In Obesity And Diabetes: This project seeks to determine the role and regulation of MMPs in activating silent growth signals leading to vascular smooth muscle cell growth in diabetes and obesity.

Glycemic Control And Stroke Outcome (GRASP Clinical Trial): In collaboration with Dr. Christiana Hall from the Department of Neurology, this NIH-funded feasibility project seeks to determine the effect of glycemic control on plasma MMPs in acute ischemic stroke patients, which may serve as a prognostic marker.

Kamakshi Sachidanandam, BPharm, - Graduate student

Mostafa Elgebaly, BPharm, - Graduate student

Weiguo Li, MD, PhD, - Postdoctoral associate

Vera Portik-Dobos, MD, - Research associate

Jim Hutchinson, BS, - Research technician

Erin Muller, BS, - Research technician

Go to PubMed

Ergul, A., Jupin, D., Johnson, M.H., and Prisant, L.M. (2006) Elevated ET-1 levels are associated with decreased arterial compliance in hypertensive patients. J. Clin. Hypertens. 8:549-554.

Song, W. and Ergul, A. (2006) Type-2 diabetes-induced changes in vascular extracellular matrix gene expression: Relation to vessel size. Cardiovasc. Diabetol. 5:3.

Sachidanandam, K., Harris, A.K., Hutchinson, J. and Ergul, A. (2006) Differential regulation of micro vs macrovascular dysfunction by endothelin-1 in type-2 diabetes. Exp. Biol. Med. 231:1016-1021.

Portik-Dobos, V., Harris, A.K., Song, W., Hutchinson, J., Johnson, M.H., Imig, J., Pollock, D.M. and Ergul, A. (2006) Endothelin antagonism prevents EGFR transactivation but not early activation of renal matrix metalloproteinase activity in type 2 diabetes. Am. J. Physiol. 290: R435-441.

Fagan, S.C., Kozak, A., Hill, W.D., Pollock, D.M., Xu, L., Johnson, M.H., Ergul, A., Hess, D.C. (2006) Hypertension after experimental cerebral ischemia: candesartan provides neurovascular protection. J. Hypertension, 24:535-539.

Harris, A., Ergul, A. and Fagan S. (2005) Effect of neutrophil depletion on gelatinase expression, edema formation, and hemorrhagic transformation after focal ischemic stroke BMC Neuroscience 6:49.

Harris, A.K., Hutchinson, J.R., Sachindanandam, K., Dorrance, A., Stepp, D., Fagan, S.C. and Ergul, A. (2005) Type 2 diabetes causes remodeling of cerebrovasculature via differential regulation of matrix metalloproteinases and collagen synthesis: role of endothelin-1. Diabetes 5:2638-2644.

Johansen, J.S., Harris, A.K., Rychly, D. and Ergul, A. (2005) Oxidative stress and use of antioxidants in diabetes:Linking basic science to clinical practice. Cardiovasc. Diabetol. 4:5.

Sachinandam, K., Fagan, S. and Ergul, A. (2005) Oxidative stress and cardiovascular disease: antioxidants and unresolved issues. Cardiovasc. Drug Rev. 23, 115-132.

Ergul, A., Johansen J.S., Stromhaug, C., Harris, A.K., Hutchinson, J., Tawfik, A., Rahimi, A., Rhim, T., Wells, B., Caldwell, W., and Anstadt, M. (2005) Vascular dysfunction of venous bypass conduits is mediated by reactive oxygen species in diabetes: Role of endothelin-1. J. Pharm. Exp. Ther. 313, 70-77.