PMID- 32649699 OWN - NLM STAT- MEDLINE DCOM- 20200908 LR - 20221207 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 15 IP - 7 DP - 2020 TI - Association of chronic inflammation and accelerated atherosclerosis among an indigenous black population with chronic kidney disease. PG - e0232741 LID - 10.1371/journal.pone.0232741 [doi] LID - e0232741 AB - INTRODUCTION: Inflammation plays a major role in the development of atherosclerosis and cardiovascular morbidity and mortality in chronic kidney disease (CKD) patients. Toll-like receptor-4 (TLR4) is a major receptor for lipopolysaccharides (endotoxin) and other ligands involved in the pathogenesis of inflammation. We determined whether endotoxin levels and the presence of TLR4 polymorphisms are associated with markers of inflammation and atherosclerosis among South African CKD patients. MATERIALS AND METHODS: Endotoxin, lipopolysaccharide binding protein (LBP), serum CD14 (sCD14), interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1) and carotid intima media thickness (CIMT) were measured in 160 participants (120 CKD patients and 40 controls). Associations between endotoxins and CIMT in the presence of sCD14, IL-8 and MCP-1, were assessed using odds ratios. Participants were screened for the presence of Asp299Gly and Thr399Ile TLR4 polymorphisms, and CIMT and inflammatory markers were compared between subjects with and without TLR4 polymorphisms. RESULTS: Endotoxin levels correlated with sCD14 (r = 0.441, p<0.001) and MCP-1 (r = 0.388, p<0.001) levels while increased CIMT was associated with MCP-1 (r = 0.448, p<0.001), sCD14 levels (r = 0.476, p<0.001), LBP (r = 0.340, p<0.001), and IL-8 (r = 0.395, p<0.001). Atherosclerosis was associated with endotoxin levels (odds ratio: 4.95; 95% confidence interval: 2.52-9.73; p<0.001), and was predicted by higher serum levels of inflammatory markers. Analysis of patients with TLR4 polymorphisms showed reduced serum levels of inflammatory markers and CIMT values compared with the patients carrying the wild type TLR4 alleles. CONCLUSION: The study demonstrated associations between circulating endotoxaemia, systemic inflammation and accelerated atherosclerosis among South African CKD patients, and showed that the atherogenic predictive power of endotoxaemia was significantly increased by the presence of elevated levels of inflammatory markers. Additional findings, which must be confirmed, suggest that TLR4 polymorphisms are associated with low levels of inflammatory markers and CIMT values. FAU - Hassan, Muzamil Olamide AU - Hassan MO AUID- ORCID: 0000-0001-8317-5241 AD - Divisions of Nephrology, Department of Internal Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. FAU - Dix-Peek, Therese AU - Dix-Peek T AD - Internal Medicine Research Laboratory, Department of Internal Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. FAU - Duarte, Raquel AU - Duarte R AD - Internal Medicine Research Laboratory, Department of Internal Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. FAU - Dickens, Caroline AU - Dickens C AD - Internal Medicine Research Laboratory, Department of Internal Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. FAU - Naidoo, Sagren AU - Naidoo S AD - Divisions of Nephrology, Department of Internal Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. FAU - Vachiat, Ahmed AU - Vachiat A AD - Division of Cardiology, Department of Internal Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. FAU - Grinter, Sacha AU - Grinter S AD - Division of Cardiology, Department of Internal Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. FAU - Manga, Pravin AU - Manga P AD - Division of Cardiology, Department of Internal Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. FAU - Naicker, Saraladevi AU - Naicker S AD - Department of Internal Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. LA - eng SI - Dryad/10.5061/dryad.xsj3tx9bg PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200710 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Toll-Like Receptor 4) SB - IM MH - Adult MH - Atherosclerosis/*complications MH - Black People/*statistics & numerical data MH - Carotid Intima-Media Thickness MH - Cohort Studies MH - Disease Susceptibility MH - Female MH - Genotype MH - Humans MH - Inflammation/complications MH - Male MH - Polymorphism, Genetic MH - Population Groups/*statistics & numerical data MH - Renal Insufficiency, Chronic/*complications/*epidemiology/genetics/metabolism MH - Risk MH - Toll-Like Receptor 4/genetics PMC - PMC7351182 COIS- We wish to state that Dr Muzamil Olamide Hassan was awarded an unrestricted research grant from AstraZeneca, which funded a 3year program of research for academic research for scientists from African countries, and the National Research Foundation of South Africa funds scientific research for academics from South Africa, and it is not a commercial entity. This does not alter our adherence to PLOS ONE policies on sharing data and materials. EDAT- 2020/07/11 06:00 MHDA- 2020/09/09 06:00 PMCR- 2020/07/10 CRDT- 2020/07/11 06:00 PHST- 2019/08/18 00:00 [received] PHST- 2020/04/03 00:00 [accepted] PHST- 2020/07/11 06:00 [entrez] PHST- 2020/07/11 06:00 [pubmed] PHST- 2020/09/09 06:00 [medline] PHST- 2020/07/10 00:00 [pmc-release] AID - PONE-D-19-23309 [pii] AID - 10.1371/journal.pone.0232741 [doi] PST - epublish SO - PLoS One. 2020 Jul 10;15(7):e0232741. doi: 10.1371/journal.pone.0232741. eCollection 2020.