Elsa I. Mangiarua, Ph.D.
Department: Pharmacology, Physiology and Toxicology
Research Cluster: Cardiovascular Disease, Obesity and Diabetes
Phone: (304) 696-6211 Fax: (304) 696-7381
E-mail: mangiaru@marshall.edu
Office: BBSC 435-M
Laboratory: BBSC 407
My laboratory is involved in two major projects:
Oxidative stress in obesity-associated hypertension
The overall goal of this research project is to elucidate the underlying mechanisms responsible for the increased susceptibility of obese individuals to develop hypertension.
Over the last several decades there has been an alarming rise in the incidence of obesity in the US. The incidence of hypertension is nearly two times greater in obese individuals than in persons of normal weight. There is also a significant correlation between weight gain and the evolution of borderline high blood pressure into established hypertension. Arterial hypertension is usually associated with a number of cardiovascular risk factors grouped in the “insulin-resistance syndrome” or “syndrome X”. Patients with Syndrome X present high plasma insulin and triglyceride levels, low high-density lipoprotein (HDL) cholesterol, glucose intolerance, central obesity, and hemostatic and fibrolytic disturbances.
The exact mechanisms for obesity’s effect on blood pressure are not known. Experimental and clinical evidence has linked an enhanced production of reactive oxygen species (ROS) to certain diseases of the cardiovascular system including hypertension. Experimental studies demonstrated that ROS, mainly through the production of superoxide anion, can cause important alterations in the cellular signal transduction systems characterized by an enhanced production of inositol triphosphate and a reduced production of cyclic GMP in cultured vascular smooth muscle cells (SMC), thus favoring vasoconstriction.
Work being done in our laboratory at the present time is aimed at elucidating the potential participation of oxidative stress in the observed increased susceptibility of obese Zucker rats to develop hypertension.
Angiogenesis in diabetic neuropathy
Peripheral neuropathy is one of the major complications of diabetes mellitus. Reduced blood flow and endoneurial hypoxia are critical components of the peripheral nerve abnormalities characteristic of diabetic neuropathy. Treatment with vasodilators or with agents with known angiogenic and neuroprotective activities, such as vascular endothelial growth factor (VEGF) and erythropoietin (EPO), alleviate some of the abnormalities in diabetic nerves. Although this suggests and important role of the vascular compartment in the nerve derangement, the specific alterations in nerve angiogenesis during diabetes remain largely unknown. To test the hypothesis that angiogenic responses in nerve endothelial cells (EC) are altered and contribute to the ensuing neuropathy in experimentally diabetic animals, and to learn how Schwann cells (SC) affect these responses, we are currently studying in collaboration with colleagues at Case University in Cleveland:
1. Changes in the extent of vascularization and in the localization of the angiogenic factors hypoxia-inducible factor-1? (HIF-1?), VEGF, and EPO in sciatic nerves from normal and experimentally diabetic rats, at different stages of the disease.
2. The angiogenic responses to VEGF and EPO in EC isolated from normal and diabetic sciatic nerves.
3. The interplay between different sciatic nerve compartments in diabetes by testing the effect of conditioned medium derived from SC grown in low or high glucose conditions, and from normal and diabetic nerve explants, on nerve EC proliferation.
Selected Publications
Mangiarua EI, Galagadera NJ, Eastham LL. Angiotensin II-induced growth effects in vascular smooth muscle in cell culture and in the aortic tunica media in organ culture. Archives of Physiology and Biochemistry 109:404-409,2001.
Morrison RG, Carpenter AB, Moore SK, Mangiarua EI, Valentovic MA, Walker EM, Wehner PS, Rhoten WB, Touchon RC, McCumbee WC. Increased sensitivity of the obese Zucker rat to deoxycorticosterone-salt-induced hypertension. Journal of Hypertension 20:2247-2255,2002.
Morrison RG, Carpenter AB, Adams VL, Mangiarua EI, Wehner PS, McCumbee WD. Progression of renal damage in the obese Zucker rat in response to deoxycorticosterone acetate-salt-induced hypertension. Annals of Clinical and Laboratory Science 35:54-65,2005.
Morrison RG, Mills CN, Moran AL, Walton CE, Walton CE, Sadek MH, Wehner PS, Mangiarua EI, Wehner PS, McCumbee WD. A moderately high fat diet promotes salt-sensitive hypertension in obese Zucker rats by impairing NO production. Clinical and Experimental Hypertension ( in press )
Walker EM Jr, Nillas MS, Mangiarua EI, Cansino S, Morrison RG, Perdue R, Triest WE, Wright GL, Studeny M, Wenher P, Rice KM, Blough ER. Age-associated changes in hearts of male Fisher 344/Brown Norway F1 rats. Annals of Clinical and Laboratory Science 36:427-437,2006.
Walker EM Jr, Epling CP, Parris C, Cansino S, Morrison RG, Wright GL, Mangiarua EI, Wehner P, Blough ER. Acetaminophen protects against iron-induced cardiac damage in gerbils. Annals of Clinical and Laboratory Science 37:22-33, 2007.