{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:50:51Z","timestamp":1787028651590,"version":"build-2736575974"},"reference-count":49,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2024,9,15]],"date-time":"2024-09-15T00:00:00Z","timestamp":1726358400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Coronary artery disease (CAD) is the leading cause of death worldwide. High-Density lipoprotein (HDL) is a well-established marker associated with CAD. The current research goes beyond the conventional HDL-C measurement in previous studies and dives into the functional intricacies of HDL. By understanding how HDL works, rather than just how much of it exists, we can better tailor diagnostic and therapeutic strategies for CAD and related conditions. Hence, the current study quantifies the serum levels of two novel HDL-associated markers, Paraoxonase-1 (PON-1) and Scavenger Receptor Class B Type 1 (SRB-1), in CAD cases vs. controls. Methods: A total of 92 subjects, including 69 CAD and 23 healthy controls, were included, based on the prevalence of the disease. Further, based on the severity of the disease, CAD cases were subcategorized as CAD-I, -II, and -III. Serum PON-1 and SRB-1 levels were measured and compared between patient and control groups. Results: The levels of PON-1 and SRB-1 (32.6 ng\/mL and 12.49 ng\/mL) were significantly lower in CAD patients vs. the healthy control, at 60.36 ng\/mL and 15.85 ng\/mL, respectively (p &lt; 0.000). A further intergroup comparison showed a statistically significant difference between the CAT-I and -III for PON-1 (p &lt; 0.025), the CAT-I and -III, and CAT-II and -III for SRB-1 (p &lt; 0.000). The receiver operating characteristics (ROC) curve showed cutoff values of 48.20 ng\/mL and 14.90 ng\/mL for PON-1 and SRB-1. Conclusions: The current study found that serum levels of HDL-associated PON-1 and SRB-1 are significantly lower in CAD cases, and were also inversely related to the increasing severity of coronary artery disease. This inference implies that serum PON-1 and SRB-1 could be used as non-invasive tools for the identification of coronary atherosclerosis and risk assessment in CAD cases.<\/jats:p>","DOI":"10.3390\/jcm13185480","type":"journal-article","created":{"date-parts":[[2024,9,16]],"date-time":"2024-09-16T11:36:37Z","timestamp":1726486597000},"page":"5480","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["High-Density Lipoprotein-Associated Paraoxonase-1 (PON-1) and Scavenger Receptor Class B Type 1 (SRB-1) in Coronary Artery Disease: Correlation with Disease Severity"],"prefix":"10.3390","volume":"13","author":[{"given":"Manish","family":"Kumar","sequence":"first","affiliation":[{"name":"Department of Pathology, King George Medical University, Lucknow 226003, Uttar Pradesh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0474-6200","authenticated-orcid":false,"given":"Wahid","family":"Ali","sequence":"additional","affiliation":[{"name":"Department of Pathology, King George Medical University, Lucknow 226003, Uttar Pradesh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kusum","family":"Yadav","sequence":"additional","affiliation":[{"name":"Department of Pathology, Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow 226003, Uttar Pradesh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swati","family":"Kaumri","sequence":"additional","affiliation":[{"name":"Department of Pathology, King George Medical University, Lucknow 226003, Uttar Pradesh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sridhar","family":"Mishra","sequence":"additional","affiliation":[{"name":"Department of Pathology, Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow 226003, Uttar Pradesh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Nardi","sequence":"additional","affiliation":[{"name":"Department of Surgical Sciences, University of Rome Tor Vergata, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8421-5065","authenticated-orcid":false,"given":"Ferdinando","family":"Iellamo","sequence":"additional","affiliation":[{"name":"Division of Cardiology and CardioLab, Department of Clinical Sciences and Translational Medicine, University of Rome Tor Vergata, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Bernardini","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, University of Rome Tor Vergata, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2360-7580","authenticated-orcid":false,"given":"Akshyaya","family":"Pradhan","sequence":"additional","affiliation":[{"name":"Lari Cardiology Center, King George Medical University, Lucknow 226003, Uttar Pradesh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0511-2621","authenticated-orcid":false,"given":"Marco Alfonso","family":"Perrone","sequence":"additional","affiliation":[{"name":"Division of Cardiology and CardioLab, Department of Clinical Sciences and Translational Medicine, University of Rome Tor Vergata, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,15]]},"reference":[{"key":"ref_1","first-page":"1008","article-title":"Number one killer: Vascular disease","volume":"1","author":"Rao","year":"2018","journal-title":"Ann. Clin. Diabetes Endocrinol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1161\/CIRCULATIONAHA.114.008729","article-title":"Cardiovascular diseases in India: Current epidemiology and future directions","volume":"133","author":"Prabhakaran","year":"2016","journal-title":"Circulation"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1093\/cvr\/cvu139","article-title":"High-density lipoproteins as modulators of endothelial cell functions: Alterations in patients with coronary artery disease","volume":"103","author":"Kratzer","year":"2014","journal-title":"Cardiovasc. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1124\/pr.58.3.1","article-title":"Functionally defective high-density lipoprotein: A novel therapeutic target at the crossroads of dyslipidemia, inflammation, and atherosclerosis","volume":"58","author":"Kontush","year":"2006","journal-title":"Pharmacol. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.1172\/JCI16777","article-title":"HDL-associated estradiol stimulates endothelial NO synthase and vasodilation in an SR-BI\u2013dependent manner","volume":"111","author":"Gong","year":"2003","journal-title":"J. Clin. Investig."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1097\/00041433-200208000-00002","article-title":"Paraoxonase gene family and coronary heart disease","volume":"13","author":"Mackness","year":"2002","journal-title":"Curr. Opin. Lipidol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1161\/01.ATV.21.4.473","article-title":"Paraoxonase and atherosclerosis","volume":"21","author":"Durrington","year":"2001","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1093\/clinchem\/32.4.671","article-title":"Distribution of paraoxon hydrolytic activity in the serum of patients after myocardial infarction","volume":"32","author":"McElveen","year":"1986","journal-title":"Clin. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.dsx.2013.02.007","article-title":"Paraoxonase-1: A better atherosclerotic risk predictor than HDL in type 2 diabetes mellitus","volume":"7","author":"Patra","year":"2013","journal-title":"Diabetes Metab. Syndr. Clin. Res. Rev."},{"key":"ref_10","first-page":"154","article-title":"Concerning the significance of paraoxonase-1 and SRB-1 genes in atherosclerosis","volume":"59","author":"Trujillo","year":"2006","journal-title":"Rev. Espa\u00f1ola Cardiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1136\/jmg.40.6.453","article-title":"Association of genetic variants in the HDL receptor, SRB-1, with abnormal lipids in women with coronary artery disease","volume":"40","author":"McCarthy","year":"2003","journal-title":"J. Med. Genet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1161\/CIRCRESAHA.112.280081","article-title":"Scavenger receptor class B type I is a plasma membrane cholesterol sensor","volume":"112","author":"Saddar","year":"2013","journal-title":"Circ. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2870","DOI":"10.1172\/JCI25327","article-title":"Hepatic expression of scavenger receptor class B type I (SR-BI) is a positive regulator of macrophage reverse cholesterol transport in vivo","volume":"115","author":"Zhang","year":"2005","journal-title":"J. Clin. Investig."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1161\/CIRCULATIONAHA.107.188208","article-title":"2007 Focused Update of the ACC\/AHA\/SCAI 2005 Guideline Update for Percutaneous Coronary Intervention: A Report of the American College of Cardiology\/American Heart Association Task Force on Practice Guidelines: 2007 Writing Group to Review New Evidence and Update the ACC\/AHA\/SCAI 2005 Guideline Update for Percutaneous Coronary Intervention, Writing on Behalf of the 2005 Writing Committee","volume":"117","author":"King","year":"2008","journal-title":"Circulation"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1001\/jama.297.3.286","article-title":"Risk factors for early myocardial infarction in South Asians compared with individuals in other countries","volume":"297","author":"Joshi","year":"2007","journal-title":"JAMA"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Geldsetzer, P., Manne-Goehler, J., Theilmann, M., Davies, J.I., Awasthi, A., Danaei, G., Gaziano, T.A., Vollmer, S., Jaacks, L.M., and Baernighausen, T. (2018). Geographic and sociodemographic variation of cardiovascular disease risk in India: A cross-sectional study of 797,540 adults. PLoS Med., 15.","DOI":"10.1371\/journal.pmed.1002581"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"19443","DOI":"10.18632\/oncotarget.14305","article-title":"Low serum paraoxonase-1 activity levels predict coronary artery disease severity","volume":"8","author":"Sun","year":"2017","journal-title":"Oncotarget"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.1161\/01.RES.0000191541.06788.bb","article-title":"Ischemic neoangiogenesis enhanced by \u03b22-adrenergic receptor overexpression: A novel role for the endothelial adrenergic system","volume":"97","author":"Iaccarino","year":"2005","journal-title":"Circ. Res."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Gupta, N., Singh, S., Maturu, V.N., Sharma, Y.P., and Gill, K.D. (2011). Paraoxonase-1 (PON-1) polymorphisms, haplotypes and activity in predicting cad risk in North-West Indian Punjabis. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0017805"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"523","DOI":"10.4103\/1947-2714.103310","article-title":"Antioxidant and anti-inflammatory role of paraoxonase-1: Implication in arteriosclerosis diseases","volume":"4","author":"Litvinov","year":"2012","journal-title":"N. Am. J. Med. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/S0021-9150(02)00423-9","article-title":"A paraoxonase gene polymorphism, PON-1 (55), as an independent risk factor for increased carotid intima-media thickness in middle-aged women","volume":"167","author":"Fortunato","year":"2003","journal-title":"Atherosclerosis"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1097\/FPC.0b013e32834cebc6","article-title":"for CARe. Relationship of Human Paraoxonase-1 (PON-1) Serum Activity and Genotype with Atherosclerosis in Individuals from the Deep South","volume":"21","author":"Coombes","year":"2011","journal-title":"Pharmacogenet. Genom."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1089\/gtmb.2010.0207","article-title":"Association of PON-1 and APOA 5 gene polymorphisms in a cohort of Indian patients having coronary artery disease with and without type 2 diabetes","volume":"15","author":"Bhaskar","year":"2011","journal-title":"Genet. Test. Mol. Biomark."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.bbrc.2008.08.106","article-title":"Macrophage paraoxonase-1 (PON-1) binding sites","volume":"376","author":"Efrat","year":"2008","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/S0008-6363(02)00659-4","article-title":"Paraoxonase-1 reduces monocyte chemotaxis and adhesion to endothelial cells due to oxidation of palmitoyl, linoleoyl glycerophosphorylcholine","volume":"57","author":"Ahmed","year":"2003","journal-title":"Cardiovasc. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.biochi.2016.10.010","article-title":"Paraoxonase and atherosclerosis-related cardiovascular diseases","volume":"132","author":"Chistiakov","year":"2017","journal-title":"Biochimie"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1016\/S0140-6736(05)61755-2","article-title":"Alloenzymes of paraoxonase and effectiveness of high-density lipoproteins in protecting low-density lipoprotein against lipid peroxidation","volume":"349","author":"Mackness","year":"1997","journal-title":"Lancet"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2088","DOI":"10.1194\/jlr.M400191-JLR200","article-title":"Scavenger receptor class B type I is solely responsible for the selective uptake of cholesteryl esters from HDL by the liver and the adrenals in mice","volume":"45","author":"Out","year":"2004","journal-title":"J. Lipid Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"33398","DOI":"10.1074\/jbc.274.47.33398","article-title":"Hepatic scavenger receptor BI promotes rapid clearance of high-density lipoprotein free cholesterol and its transport into bile","volume":"274","author":"Ji","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"4619","DOI":"10.1073\/pnas.95.8.4619","article-title":"Targeted mutation reveals a central role for SR-BI in hepatic selective uptake of high-density lipoprotein cholesterol","volume":"95","author":"Varban","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"12610","DOI":"10.1073\/pnas.94.23.12610","article-title":"A targeted mutation in the murine gene encoding the high-density lipoprotein (HDL) receptor scavenger receptor class B type I reveals its key role in HDL metabolism","volume":"94","author":"Rigotti","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1161\/hh0302.104462","article-title":"Loss of SR-BI expression leads to the early onset of occlusive atherosclerotic coronary artery disease, spontaneous myocardial infarctions, severe cardiac dysfunction, and premature death in apolipoprotein E\u2013deficient mice","volume":"90","author":"Braun","year":"2002","journal-title":"Circ. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1589","DOI":"10.1161\/01.ATV.0000083343.19940.A0","article-title":"Scavenger receptor class B type I\u2013mediated protection against atherosclerosis in LDL receptor\u2013negative mice involve its expression in bone marrow\u2013derived cells","volume":"23","author":"Covey","year":"2003","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1161\/01.ATV.20.4.1068","article-title":"Increased LDL Cholesterol and Atherosclerosis in LDL Receptor\u2013Deficient Mice with Attenuated Expression of Scavenger Receptor B1","volume":"20","author":"Huszar","year":"2000","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"32920","DOI":"10.1074\/jbc.273.49.32920","article-title":"Liver-specific overexpression of scavenger receptor BI decreases levels of very low-density lipoprotein ApoB, low-density lipoprotein ApoB, and high-density lipoprotein in transgenic mice","volume":"273","author":"Wang","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"7165","DOI":"10.1074\/jbc.274.11.7165","article-title":"Lower plasma levels and accelerated clearance of high-density lipoprotein (HDL) and non-HDL cholesterol in scavenger receptor class B type I transgenic mice","volume":"274","author":"Ueda","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1194\/jlr.M200026-JLR200","article-title":"Overexpression of SR-BI by adenoviral vector promotes clearance of apoA-I, but not apoB, in human apoB transgenic mice","volume":"43","author":"Webb","year":"2002","journal-title":"J. Lipid Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1038\/387414a0","article-title":"Overexpression of the HDL receptor SR-BI alters plasma HDL and bile cholesterol levels","volume":"387","author":"Kozarsky","year":"1997","journal-title":"Nature"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1161\/01.ATV.20.3.721","article-title":"Gene transfer and hepatic overexpression of the HDL receptor SR-BI reduces atherosclerosis in the cholesterol-fed LDL receptor\u2013deficient mouse","volume":"20","author":"Kozarsky","year":"2000","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.1126\/science.aad3517","article-title":"Rare variant in scavenger receptor BI raises HDL cholesterol and increases risk of coronary heart disease","volume":"351","author":"Zanoni","year":"2016","journal-title":"Science"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1161\/CIRCRESAHA.120.318793","article-title":"Inherited variants in SCARB1 cause severe early onset coronary artery disease","volume":"129","author":"Koenig","year":"2021","journal-title":"Circ. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1038\/s41586-019-1140-4","article-title":"SRB-1 drives endothelial cell LDL transcytosis via DOCK4 to promote atherosclerosis","volume":"569","author":"Huang","year":"2019","journal-title":"Nature"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.gene.2018.05.072","article-title":"Obesity-induced overexpression of miRNA-24 regulates cholesterol uptake and lipid metabolism by targeting SRB-1","volume":"668","author":"Wang","year":"2018","journal-title":"Gene"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1146\/annurev-physiol-021317-121550","article-title":"SRB-1: A unique multifunctional receptor for cholesterol influx and efflux","volume":"80","author":"Shen","year":"2018","journal-title":"Annu. Rev. Physiol."},{"key":"ref_45","unstructured":"Jiang, C. (2024, August 13). The Role of SRB-1 in Lipid Metabolism and Inflammation in 3T3-L1 Adipocytes. Available online: https:\/\/opencommons.uconn.edu\/usp_projects\/35."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"234","DOI":"10.23736\/S0025-7826.19.03531-2","article-title":"Inflammation, oxidative stress and gene expression: The postprandial approach in professional soccer players to reduce the risk of muscle injuries and early atherosclerosis","volume":"72","author":"Perrone","year":"2019","journal-title":"Med. Sport"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"221","DOI":"10.2459\/JCM.0000000000001451","article-title":"Improving diagnostic assessments in the ever-changing landscape of atherosclerosis","volume":"24","author":"Sawalha","year":"2023","journal-title":"J. Cardiovasc. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"419","DOI":"10.2459\/JCM.0000000000000816","article-title":"Effects of postprandial hydroxytyrosol and derivates on oxidation of LDL, cardiometabolic state and gene expression: A nutrigenomic approach for cardiovascular prevention","volume":"20","author":"Perrone","year":"2019","journal-title":"J. Cardiovasc. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e156","DOI":"10.2459\/JCM.0000000000001450","article-title":"Evolving concepts in the pathophysiology of atherosclerosis: From endothelial dysfunction to thrombus formation through multiple shades of inflammation","volume":"24","author":"Cimmino","year":"2023","journal-title":"J. Cardiovasc. Med."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/18\/5480\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:57:03Z","timestamp":1760111823000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/18\/5480"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,15]]},"references-count":49,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2024,9]]}},"alternative-id":["jcm13185480"],"URL":"https:\/\/doi.org\/10.3390\/jcm13185480","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,15]]}}}