Chronic kidney disease (CKD) patients are at greater risk of cardiovascular disease, given that renal insufficiency is associated with impaired heart vascularisation. We demonstrated that soluble VEGF receptor 1 (sFlt1) levels, a VEGF antagonist that impairs angiogenesis, are increased in CKD patients as well as in the 5/6 nephrectomised rat. The mechanisms that upregulate sFlt-1 in CKD are not completely understood. However, it is known that secretion of sFlt-1 is stimulated via angiotensin II receptor (AT1R) activation and subsequent calcineurin signalling in different cell types. In this context, we have raised the following hypotheses: 1) increased sFlt-1 levels lead to impaired heart angiogenesis; 2) the AT1R blocker and/or a calcineurin inhibitor (CNI) and/or a specific antibody against sFlt1 are able to normalise sFlt-1 levels; and consequently 3) avoid loss of heart vessels. 4) In addition, AT1R blocker therapy should be able to avoid heart remodelling. By infusion of sFlt-1 in control rats and by using the 5/6 nephrectomised rat model, we aim to investigate these hypotheses and study the possible use of the AT1R blocker as a therapeutic strategy against cardiovascular disease in CKD.
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