Hemodialysis is the most widely used option in chronic dialysis treatment and requires a suitable vascular access. Unfortunately, this vascular access suffers from a high number of failures... Show moreHemodialysis is the most widely used option in chronic dialysis treatment and requires a suitable vascular access. Unfortunately, this vascular access suffers from a high number of failures responsible for a high morbidity and health care costs. However, the exact pathophysiology remains unclear. In order to unravel the mechanisms of arteriovenous fistula failure we developed a novel murine model of arteriovenous fistula failure. Using this model, we studied the effects of vascular remodeling in mice that were haplodeficient for the eln gene. The role of inflammation in arteriovenous remodeling was also investigated by administrating liposomal prednisolone and by incorporating RP105 knockout mice. Show less
Wezel, A.; Velden, D. van der; Maassen, J.M.; Lagraauw, H.M.; Vries, M.R. de; Karper, J.C.; ... ; Quax, P.H.A. 2015
The studies in this thesis are performed to provide additional and improved insight into the effects and interplay of dietary lipids and metabolic inflammation on cardiac performance in the... Show moreThe studies in this thesis are performed to provide additional and improved insight into the effects and interplay of dietary lipids and metabolic inflammation on cardiac performance in the presence or absence of atherosclerosis and myocardial infarctions (MI). We show that high-fat diet feeding has mild but significant detrimental effects on cardiac function. In contrast to our expectations, this effect is not likely to be mediated by Toll-like receptor 2 or Toll-like receptor 4. Also, we demonstrated in mice that high-fat diet feeding does not significantly aggravate cardiac dysfunction post-MI. Deficiency of RP105, a modulator of inflammation, improved cardiac function after induction of MI. In addition, ABCA1 had adverse effects on cardiac function post-MI, possibly via a reduced activation of immune cells. This confirms the important role of inflammation in recovery after MI. Furthermore, we elucidated a possible reason for the failure of niacin in recent clinical trials and found that niacin__s anti-atherogenic properties are most potent by lowering LDL-cholesterol on top of statin treatment. Altogether, these results provide novel insights and targets for the prevention or treatment of cardiovascular diseases. Show less
