Impaired Delivery of Cholesterol Effluxed From Macrophages to Hepatocytes by Serum From CKD Patients May Underlie Increased Cardiovascular Disease Risk
| العنوان: | Impaired Delivery of Cholesterol Effluxed From Macrophages to Hepatocytes by Serum From CKD Patients May Underlie Increased Cardiovascular Disease Risk |
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| المؤلفون: | Jing Wang, Daniel E. Carl, Salvatore Carbone, Graham T. Gipson, Dave L. Dixon, Shobha Ghosh, Ion S. Jovin, Todd W.B. Gehr |
| المصدر: | Kidney International Reports, Vol 5, Iss 2, Pp 199-210 (2020) Kidney International Reports |
| بيانات النشر: | Elsevier BV, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | medicine.medical_specialty, 030232 urology & nephrology, Renal function, 030204 cardiovascular system & hematology, lcsh:RC870-923, Coronary artery disease, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, Translational Research, medicine, Risk factor, serum cholesterol efflux capacity, Creatinine, business.industry, Cholesterol, Reverse cholesterol transport, lcsh:Diseases of the genitourinary system. Urology, medicine.disease, cardiovascular disease risk, reverse cholesterol transport, Endocrinology, chemistry, Nephrology, delivery of cholesterol to the liver, lipids (amino acids, peptides, and proteins), business, chronic kidney disease, Kidney disease, Lipoprotein |
| الوصف: | Introduction Although chronic kidney disease (CKD) is associated with increased risk for coronary artery disease (CAD), the underlying mechanisms are not completely defined. In the present study, we tested the hypothesis that flux of cholesterol from macrophage foam cells to liver is impaired in subjects with CKD. Methods Consecutive healthy patients, patients with at least 1 CAD risk factor, patients with established CAD, and patients with CKD stages G3 to G5 (n ≥ 15/group) were recruited prospectively. The ability of total patient serum without any modifications to (i) facilitate efflux of cholesterol from human THP1-macrophage foam cells under physiological conditions (cholesterol efflux capacity [CEC]) and (ii) to deliver this effluxed cholesterol to primary hepatocytes with physiological expression of high-density lipoprotein (HDL) receptor SR-BI (capacity to deliver cholesterol to hepatocytes [CDCH]) was evaluated. Results Although healthy patients, patients with at least 1 CAD risk factor, and patients with established CAD all showed similar CEC, patients with CKD showed significantly higher CEC. CDCH was significantly lower in all groups compared with the healthy patients; however, when corrected for higher CEC, CDCH in patients with CKD was significantly lower than in patients with CAD. CDCH correlated with age, body mass index, metabolic parameters, inflammatory markers, and kidney function markers (estimated glomerular filtration rate [eGFR], serum creatinine, and serum cystatin C). Conclusions These results suggest that aberrations in delivery of cholesterol effluxed from macrophage foam cells to liver for final elimination or the last step of reverse cholesterol transport, may underlie the increased risk of CAD in patients with CKD. Graphical abstract |
| تدمد: | 2468-0249 |
| DOI: | 10.1016/j.ekir.2019.11.003 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2315608dbffbb7cc3a4387d50e9ab9fa https://doi.org/10.1016/j.ekir.2019.11.003 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....2315608dbffbb7cc3a4387d50e9ab9fa |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 24680249 |
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| DOI: | 10.1016/j.ekir.2019.11.003 |