Association of chronic inflammation and accelerated atherosclerosis among an indigenous black population with chronic kidney disease
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 inflammatio...
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| Veröffentlicht in: | PloS one 2020-07, Vol.15 (7), p.e0232741-e0232741 |
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| creator | Hassan, Muzamil Olamide Dix-Peek, Therese Duarte, Raquel Dickens, Caroline Naidoo, Sagren Vachiat, Ahmed Grinter, Sacha Manga, Pravin Naicker, Saraladevi |
| description | 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.
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.
Endotoxin levels correlated with sCD14 (r = 0.441, p |
| doi_str_mv | 10.1371/journal.pone.0232741 |
| format | Article |
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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.
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.
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.]]></description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0232741</identifier><identifier>PMID: 32649699</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adult ; Arteriosclerosis ; Atherosclerosis ; Atherosclerosis - complications ; Biology and Life Sciences ; Blacks - statistics & numerical data ; Blood pressure ; Cardiology ; Cardiovascular diseases ; Carotid Intima-Media Thickness ; CD14 antigen ; Cohort Studies ; Confidence intervals ; Disease Susceptibility ; Endotoxins ; Female ; Genotype ; Health sciences ; Humans ; Inflammation ; Inflammation - complications ; Interleukin 8 ; Internal medicine ; Kidney diseases ; Kidneys ; Laboratories ; Levels ; Lipopolysaccharides ; Male ; Markers ; Medicine ; Medicine and Health Sciences ; Monocyte chemoattractant protein ; Monocyte chemoattractant protein 1 ; Monocytes ; Morbidity ; Nephrology ; Pathogenesis ; People and Places ; Polymorphism, Genetic ; Population Groups - statistics & numerical data ; Proteins ; Receptors ; Renal Insufficiency, Chronic - complications ; Renal Insufficiency, Chronic - epidemiology ; Renal Insufficiency, Chronic - genetics ; Renal Insufficiency, Chronic - metabolism ; Risk ; Serum levels ; Thickness measurement ; TLR4 protein ; Toll-Like Receptor 4 - genetics ; Toll-like receptors</subject><ispartof>PloS one, 2020-07, Vol.15 (7), p.e0232741-e0232741</ispartof><rights>2020 Hassan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2020 Hassan et al 2020 Hassan et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c526t-b1d372a995a4589370b8ae3751647e00ce97b6501e25567fbf1cb5285eb1978e3</citedby><cites>FETCH-LOGICAL-c526t-b1d372a995a4589370b8ae3751647e00ce97b6501e25567fbf1cb5285eb1978e3</cites><orcidid>0000-0001-8317-5241</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7351182/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7351182/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79569,79570</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32649699$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hassan, Muzamil Olamide</creatorcontrib><creatorcontrib>Dix-Peek, Therese</creatorcontrib><creatorcontrib>Duarte, Raquel</creatorcontrib><creatorcontrib>Dickens, Caroline</creatorcontrib><creatorcontrib>Naidoo, Sagren</creatorcontrib><creatorcontrib>Vachiat, Ahmed</creatorcontrib><creatorcontrib>Grinter, Sacha</creatorcontrib><creatorcontrib>Manga, Pravin</creatorcontrib><creatorcontrib>Naicker, Saraladevi</creatorcontrib><title>Association of chronic inflammation and accelerated atherosclerosis among an indigenous black population with chronic kidney disease</title><title>PloS one</title><addtitle>PLoS One</addtitle><description><![CDATA[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.
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.
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.
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.]]></description><subject>Adult</subject><subject>Arteriosclerosis</subject><subject>Atherosclerosis</subject><subject>Atherosclerosis - complications</subject><subject>Biology and Life Sciences</subject><subject>Blacks - statistics & numerical data</subject><subject>Blood pressure</subject><subject>Cardiology</subject><subject>Cardiovascular diseases</subject><subject>Carotid Intima-Media Thickness</subject><subject>CD14 antigen</subject><subject>Cohort Studies</subject><subject>Confidence intervals</subject><subject>Disease Susceptibility</subject><subject>Endotoxins</subject><subject>Female</subject><subject>Genotype</subject><subject>Health sciences</subject><subject>Humans</subject><subject>Inflammation</subject><subject>Inflammation - complications</subject><subject>Interleukin 8</subject><subject>Internal medicine</subject><subject>Kidney diseases</subject><subject>Kidneys</subject><subject>Laboratories</subject><subject>Levels</subject><subject>Lipopolysaccharides</subject><subject>Male</subject><subject>Markers</subject><subject>Medicine</subject><subject>Medicine and Health Sciences</subject><subject>Monocyte chemoattractant protein</subject><subject>Monocyte chemoattractant protein 1</subject><subject>Monocytes</subject><subject>Morbidity</subject><subject>Nephrology</subject><subject>Pathogenesis</subject><subject>People and Places</subject><subject>Polymorphism, Genetic</subject><subject>Population Groups - statistics & numerical data</subject><subject>Proteins</subject><subject>Receptors</subject><subject>Renal Insufficiency, Chronic - complications</subject><subject>Renal Insufficiency, Chronic - epidemiology</subject><subject>Renal Insufficiency, Chronic - genetics</subject><subject>Renal Insufficiency, Chronic - metabolism</subject><subject>Risk</subject><subject>Serum levels</subject><subject>Thickness measurement</subject><subject>TLR4 protein</subject><subject>Toll-Like Receptor 4 - genetics</subject><subject>Toll-like receptors</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNptkktv1DAQxyMEoqXwDRBE4sJlFz9iO74gVRWPSpW4wNmaOONdbxN7sZOi3vvB62W3qxZxsUfj__w8r6p6S8mSckU_beKcAgzLbQy4JIwz1dBn1SnVnC0kI_z5I_ukepXzhhDBWylfViecyUZLrU-ru_Oco_Uw-Rjq6Gq7TjF4W_vgBhjHvR9CX4O1OGCCCYs9rTHFbIfd6XMNYwyroipRvV9hiHOuuwHsdb2N23nYQ_74aX3EX_s-4G3d-4yQ8XX1wsGQ8c3hPqt-ff3y8-L74urHt8uL86uFFUxOi472XDHQWkAjWs0V6VpArgSVjUJCLGrVSUEoMiGkcp2jthOsFdhRrVrkZ9X7PXc7xGwODcyGNYxxXbCkKC73ij7CxmyTHyHdmgje_HXEtDKQJl8qN44IJmjLhALWOCc0pxzB0b4rOTnpCuvz4be5G7G3GKYEwxPo05fg12YVb4zighZwAXw8AFL8PWOezOhzmcIAAUuLd3lzIiVvVJF--Ef6_-qavcqWueWE7pgMJWa3VA9RZrdU5rBUJezd40KOQQ9bxO8BqTvNpA</recordid><startdate>20200710</startdate><enddate>20200710</enddate><creator>Hassan, Muzamil Olamide</creator><creator>Dix-Peek, Therese</creator><creator>Duarte, Raquel</creator><creator>Dickens, Caroline</creator><creator>Naidoo, Sagren</creator><creator>Vachiat, Ahmed</creator><creator>Grinter, Sacha</creator><creator>Manga, Pravin</creator><creator>Naicker, Saraladevi</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0001-8317-5241</orcidid></search><sort><creationdate>20200710</creationdate><title>Association of chronic inflammation and accelerated atherosclerosis among an indigenous black population with chronic kidney disease</title><author>Hassan, Muzamil Olamide ; Dix-Peek, Therese ; Duarte, Raquel ; Dickens, Caroline ; Naidoo, Sagren ; Vachiat, Ahmed ; Grinter, Sacha ; Manga, Pravin ; Naicker, Saraladevi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c526t-b1d372a995a4589370b8ae3751647e00ce97b6501e25567fbf1cb5285eb1978e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Adult</topic><topic>Arteriosclerosis</topic><topic>Atherosclerosis</topic><topic>Atherosclerosis - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hassan, Muzamil Olamide</au><au>Dix-Peek, Therese</au><au>Duarte, Raquel</au><au>Dickens, Caroline</au><au>Naidoo, Sagren</au><au>Vachiat, Ahmed</au><au>Grinter, Sacha</au><au>Manga, Pravin</au><au>Naicker, Saraladevi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Association of chronic inflammation and accelerated atherosclerosis among an indigenous black population with chronic kidney disease</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2020-07-10</date><risdate>2020</risdate><volume>15</volume><issue>7</issue><spage>e0232741</spage><epage>e0232741</epage><pages>e0232741-e0232741</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract><![CDATA[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.
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.
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.
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.]]></abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>32649699</pmid><doi>10.1371/journal.pone.0232741</doi><orcidid>https://orcid.org/0000-0001-8317-5241</orcidid><oa>free_for_read</oa></addata></record> |
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| recordid | cdi_plos_journals_2422399950 |
| source | Public Library of Science (PLoS) Journals Open Access; MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Adult Arteriosclerosis Atherosclerosis Atherosclerosis - complications Biology and Life Sciences Blacks - statistics & numerical data Blood pressure Cardiology Cardiovascular diseases Carotid Intima-Media Thickness CD14 antigen Cohort Studies Confidence intervals Disease Susceptibility Endotoxins Female Genotype Health sciences Humans Inflammation Inflammation - complications Interleukin 8 Internal medicine Kidney diseases Kidneys Laboratories Levels Lipopolysaccharides Male Markers Medicine Medicine and Health Sciences Monocyte chemoattractant protein Monocyte chemoattractant protein 1 Monocytes Morbidity Nephrology Pathogenesis People and Places Polymorphism, Genetic Population Groups - statistics & numerical data Proteins Receptors Renal Insufficiency, Chronic - complications Renal Insufficiency, Chronic - epidemiology Renal Insufficiency, Chronic - genetics Renal Insufficiency, Chronic - metabolism Risk Serum levels Thickness measurement TLR4 protein Toll-Like Receptor 4 - genetics Toll-like receptors |
| title | Association of chronic inflammation and accelerated atherosclerosis among an indigenous black population with chronic kidney disease |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-13T14%3A58%3A56IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Association%20of%20chronic%20inflammation%20and%20accelerated%20atherosclerosis%20among%20an%20indigenous%20black%20population%20with%20chronic%20kidney%20disease&rft.jtitle=PloS%20one&rft.au=Hassan,%20Muzamil%20Olamide&rft.date=2020-07-10&rft.volume=15&rft.issue=7&rft.spage=e0232741&rft.epage=e0232741&rft.pages=e0232741-e0232741&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0232741&rft_dat=%3Cproquest_plos_%3E2423066347%3C/proquest_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2422399950&rft_id=info:pmid/32649699&rft_doaj_id=oai_doaj_org_article_f052518257a24ff59313eaf1dbae3f6f&rfr_iscdi=true |