| Autor: |
Padalkar, Mugdha V, Gelfman, Ylona, Kasiyanyk, Mariya, Kaungumpillil, Neil, Singh, Mohnish, Schram, Eric, Tsivitis, Alexandra, Savinova, Olga V |
| Zdroj: |
Circulation (Ovid); November 2022, Vol. 146 Issue: Supplement 1 pA15473-A15473, 1p |
| Abstrakt: |
Introduction:Patients with chronic kidney disease (CKD) experience significant cardiovascular morbidity and mortality. Vascular calcification is a hallmark of CKD and a strong predictor of atherosclerotic cardiovascular disease.Hypothesis:We hypothesize that CKD-induced vascular calcification potentiates atherosclerosis.Methods:First, wished to conduct a pilot study to confirm that a co-treatment of the low-density protein receptor mutant mice (Ldlrwhc) with a 0.2% adenine in a western diet will produce accelerated atherosclerosis, consistent with a well-known phenotype in the 5/6 nephrectomy model on an ApoE or Ldlr knockout background. Then we developed a two-step non-surgical mouse model in which the induction of calcification by a 0.2% adenine treatment was followed by western diet-induced hyperlipidemia.Results:Contrary to expected, the adenine and western diet (W+A) co-treatment resulted in a striking reduction of plasma triglycerides (TG), aortic root atherosclerosis, and liver lipids despite a fully penetrant CKD phenotype with tubulointerstitial damage, increased blood urea nitrogen, hyperphosphatemia, polyuria, vascular calcification, and osteoporosis. The two-step induction of CKD and atherosclerosis demonstrated partially normalized but reduced plasma triglycerides and liver lipid content, polyurea, and polydipsia in CKD mice, and there was no difference in atherosclerotic burden or plaque calcification between the groups. Interestingly we observed an increase in food and calorie intake and 24-hour glucose excretion in the urine in the pre-treated group compared with mice on a western diet without pre-treatment, while plasma glucose levels were not different between the groups.Conclusion:The paradoxical lack of dyslipidemia in mice treated with adenine provides an insight into the potential effects of tubulointerstitial kidney disease and nephrogenic diabetes incipits on lipid metabolism and atherosclerosis. 1 |
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