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| Assistant Professor |
| Office:
919-966-1338 |
| E-mail:
ntakaha@med.unc.edu |
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| Our research focuses on the roles of genes (especially those that regulate blood pressure) on the metabolic syndrome, diabetic nephropathy, and preeclampsia in humans using genetically engineered mouse models and computer simulations. |
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| The Metabolic syndrome: The overactive renin angiotensin system is suggested to cause the metabolic syndrome. Our mice lacking renin are lean, insulin sensitive, and resistant to diet-induced obesity without changes in food intake and physical activity. They have high metabolic rate, and gastrointestinal loss of dietary fat. The results of our study suggest new ways of treating the metabolic syndrome. Renin inhibitors currently under development for the treatment of hypertension may have favorable effects on obesity and insulin sensitivity and its associated metabolic and cardiovascular consequences. The angiotensin II-independent direct effects of renin on the metabolic syndrome are currently being investigated. |
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| Diabetic nephropathy (DN): DN greatly increases the risk of stroke and heart attack. Human endothelial nitric oxide synthase (eNOS) polymorphisms that lead to lower eNOS expression are associated with advanced DN. We found that the absence of eNOS in diabetic mice accelerates DN, especially glomerulosclerosis and interstitial fibrosis, without increasing oxidative stress. Moreover, feeding mice a high fat diet exacerbates this phenotype. eNOS-/- diabetic mouse is one of the most severe animal models of DN. Its mechanisms are under investigation. |
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| Preeclampsia: sFlt-1 is a soluble form of the receptor for vascular endothelial growth factor (VEGF) and placental growth factor (PlGF). sFlt-1 is highly expressed in placentas of women with preeclampsia. It is a truncated form of Flt-1, secreted into the circulation, and works as a VEGF/PlGF antagonist. Injecting an adenovirus that expresses sFlt-1 into the tail veins of mice caused marked proteinuria and decreased urine volume. Blood pressure of these mice was more than 200 mmHg. Kidney histology shows exactly the same pathologic features as human preeclampsia. The roles of eNOS, angiotensin converting enzyme, and other genes are being studied. |
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