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Vascular (Dys-)Function as a Determinant of Susceptibility to Diabetic Nephropathy: a Focus on Myogenic Constriction


Title:   Vascular (Dys-)Function as a Determinant of Susceptibility to Diabetic Nephropathy: a Focus on Myogenic Constriction.
Investigator:  M Hamidi Shishvan
Promotor:   RH Henning
Co-promoter(es):  LE Deelman, JH Buikema 
Summary:  Endothelial dysfunction (ED) seems to be a crucial mediator of increased cardiovascular risk observed among patients with chronic kidney disease (CKD). Importantly, systemic ED does not only occur in patients with severe renal failure, but also in individuals with earlier stages of CKD. Close association between microalbuminuria and systemic ED renders vascular function an important marker for the severity of cardiovascular damage. Furthermore, alterations of the renal endothelium might be actively involved in the progression of renal end-organ damage. We previously showed that interindividual variability in renal endothelial function (EF) of healthy rats predicted the susceptibility to renal damage induced by 5/6 nephrectomy (Nx) and efficacy of renoprotective treatment (Ochodnicky et al., 2006). We extendly hypothesize that the predictive value of vascular (dys-)function as a determinant of susceptibility to end-organ damage is not restricted to the endothelial function but (1) additionally encloses myogenic constriction (MC) in smooth muscle cell function, and (2) also applies to renal damage induced by other conditions. With reference to the growing number of people worldwide expected to develop type-2 diabetes (DM-2) and suffer from the micro- and macrovascular complications hereof (e.g. diabetic nephropathy), the project aims to address this hypothesis employing (mice and rat) models of metabolic syndrome (MBS) and DM-2. 
Financing:  GUIDE Bursary
Start:  1-10-2010
End:  1-10-2014 

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