Research Abstract:
The goal of my laboratory is to pursue a series of studies in the coming years focused mainly in two mechanisms that we believe are critical in the pathophysiology of cardiovascular disease in patients with type 2 DM and prediabetes: Vitamin D deficiency and tissue glucocorticoid excess.
Patients with prediabetes and Type 2 DM have a higher prevalence of vitamin D deficiency and hypertension compared to the general population. Animal and human studies have shown that vitamin D improves peripheral insulin action, suppresses the renin-angiotensin system and decreases vascular inflammatory factors, mechanisms responsible for increased blood pressure (BP). However, there is lack of evidence as to whether the increased prevalence of hypertension and atherosclerosis in patients with diabetes or pre-diabetes is truly influenced by vitamin D deficiency. Our laboratory is using multiple animal models, novel molecular biology techniques and classical physiology to assess whether an alteration in the expression of genes related to vitamin D metabolism are responsible for the development of these diseases. The second major area of our laboratory interest is to find the mechanism by which glucocorticoid-induced hypertension and atherosclerosis. To define this mechanism, we are using mouse model with selective modulation of the glucocorticoid receptors in critical tissues to develop these diseases. Our long term goal is to continue translating into humans our previous and future animal research findings about novel mechanisms responsible for insulin resistance, hypertension and atherosclerosis.
Selected Publications:
Oh J, Weng S,Felton S, Bhandare S, Butler B, Proctor B, Petty M, Chen Z, Bernal-Mizrachi L, Bernal-Mizrachi C. Vitamin D inhibits foam cell formation and suppresses macrophage cholesterol uptake in patients with type 2 diabetes. Circulation 2009 120(8):687-98.
Bernal-Mizrachi C, Arbelaez AM, Bandhare S. Vitamin D Deficiency. 2nd Edition Washington Manual Endocrinology Subspecialty Consult. Lippincott Williams & Wilkins 2008 (24): 185-199.
Gates AC*, Bernal-Mizrachi C*, Chinault SL*, Feng C, Schneider JG. Coleman T, Malone JP Townsend RR, Chakravarthy MV Semenkovich CF. Respiratory Uncoupling in Skeletal Muscle Delays Deathand Diminishes Age-Related Disease. Cell Metabolism 2007 6(6):497-505.
Bernal-Mizrachi C, Gates, A, Weng S, Imamura T, Knutsen RH, Coleman T, Muglia LJ, Semenkovich: Vascular uncoupling increases superoxide, blood pressure and atherosclerosis. Nature 2005 435:502-506.
Bernal-Mizrachi C, Weng S, Feng C, Finck BN, Knutsen RH, Leone TC, Coleman T, Mechanm RP, Kelly DP, Semenkovich CF: Dexamethasone induction of hypertension and diabetes in PPAR-alpha dependent in LDL receptor-null mice. Nat Med 2003 8:1069-1075.
Last Updated: 08/27/2009 |