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Interests
Teaching: Laboratory Animal Medicine; Animal Models of Human Disease; Comparative Atherosclerosis; Cardiovascular Disease
Research: Comparative Atherosclerosis; Diabetes Mellitus in Monkeys; Animal Models of Human Disease; Women's Health; Cardiovascular Disease
Clinical: Cardiovascular Disease; Diabetes Mellitus; Nonhuman Primate Medicine
Current Research Project: Atherosclerosis, Estrogens, Diabetes
My major research interest is the role of hormonal influences on the cellular and biochemical aspects of atherosclerosis, centering on the metabolism of low density lipoprotein (LDL) by the arterial wall.
Using female cynomolgus monkeys fed a moderately atherogenic diet, hormone replacement therapy (estrogen and cyclic progesterone) was found to decrease significantly the accumulation of both degradation products of LDL and undegraded LDL in coronary and other arteries. Furthermore, the coronary arteries of hormone-deficient monkeys showed a greater increase in LDL degradation than other arteries, which accurately predicts the increase in coronary artery atherosclerosis in postmenopausal women.
In another study using oral contraceptive therapy in premenopausal monkeys, the preparations Ovral and Triphasil both decreased arterial LDL accumulation, despite causing a more atherogenic lipoprotein profile (i.e., decreased HDL cholesterol). This decrease in LDL degradation and accumulation is one mechanism by which we believe that hormone therapy may decrease the incidence of coronary heart disease in women.
The changes in arterial LDL metabolism with hormone treatment are not explained by beneficial changes in plasma lipid and lipoprotein concentrations and occurred without changes in indices of endothelial injury. However, a consistent finding with estrogen treatments is a decrease in LDL size which may also affect the atherogenicity of the particles. The change in LDL size may be related to altered hepatic metabolism.
A second interest I am pursuing is the relationship between insulin resistance and the exacerbation of atherosclerosis. We have found the addition of some progestins to estrogen therapy increases insulin resistance. We are also characterizing the diabetic monkeys in our colony and studying the effects of glucose metabolism and the effects of hyper- insulinemia and caloric restriction on disease progression
Recent Publications:
Kavanagh K, Jones KL, Sawyer J, Kelley K, Carr JJ, Wagner JD, Rudel LL. Trans fat diet induces abdominal obesity and changes in insulin sensitivity in monkeys. Obesity (Silver Spring). 2007 Jul;15(7):1675-84.
Kavanagh K, Fairbanks LA, Bailey JN, Jorgensen MJ, Wilson M, Zhang L, Rudel LL, Wagner JD. Characterization and heritability of obesity and associated risk factors in vervet monkeys. Obesity (Silver Spring). 2007 Jul;15(7):1666-74.
Shadoan MK, Kavanagh K, Zhang L, Anthony MS, Wagner JD. Addition of medroxyprogesterone acetate to conjugated equine estrogens results in insulin resistance in adipose tissue. Metabolism. 2007 Jun;56(6):830-7.
Krishnan SG, Valderrama E, Wagner JD, Mattana J, Shah HH, Appel G, Singhal PC. Monoclonal gammopathy presenting as recurrent nephrotic syndrome: therapeutic implications. Am J Med Sci. 2007 May;333(5):313-6.
Bezhani S, Winter C, Hershman S, Wagner JD, Kennedy JF, Kwon CS, Pfluger J, Su Y, Wagner D. Unique, shared, and redundant roles for the Arabidopsis SWI/SNF chromatin remodeling ATPases BRAHMA and SPLAYED. Plant Cell. 2007 Feb;19(2):403-16. Epub 2007 Feb 9.
Publications:
For a listing of additional publications, refer to PubMed, a service provided by the National Library of Medicine
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