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We aimed to identify alterations of the proteins in high\u2010density lipoproteins (HDL) associated with HDL dysfunction in PAD patients. HDL<jats:sub>2<\/jats:sub> and HDL<jats:sub>3<\/jats:sub> were isolated from plasma of PAD patients with\/without DM (PAD\u2010DM\/PAD) and healthy subjects (<jats:italic>N<\/jats:italic>). Apolipoprotein AI (ApoAI), ApoAII, ApoCIII, clusterin (CLU), paraoxonase 1 (PON1), myeloperoxidase (MPO), and ceruloplasmin (CP) were measured in HDL<jats:sub>2<\/jats:sub>\/HDL<jats:sub>3<\/jats:sub> and plasma. Oxidation and glycation of the analyzed proteins were assessed as malondialdehyde\u2010protein adducts (MDA) and advanced glycation end\u2010products (AGE), respectively. The anti\u2010inflammatory effect of HDL<jats:sub>3<\/jats:sub> was estimated as its potential to reduce monocyte adhesion to tumor necrosis factor \u03b1\u2010activated endothelial cells. We show that in PAD patients compared to <jats:italic>N<\/jats:italic> subjects: (i) HDL<jats:sub>2<\/jats:sub> presented increased levels of MDA\u2010PON1, AGE\u2010PON1, AGE\u2010ApoAI, ApoAII, ApoCIII, and CP levels, and decreased PON1 levels; (ii) HDL<jats:sub>3<\/jats:sub> had increased levels of MDA\u2010 and AGE\u2010CLU and \u2010ApoAI, MDA\u2010PON1, ApoCIII, CLU, MPO, CP, and reduced PON1 levels. All these alterations were exacerbated by DM. These changes were more pronounced in HDL<jats:sub>3<\/jats:sub>, which had reduced anti\u2010inflammatory potential in PAD and became pro\u2010inflammatory in PAD\u2010DM. In PAD patients' plasma, CLU levels and MPO specific activity increased, while PON1 specific activity decreased. In conclusion, HDL function is altered in PAD patients due to multiple modifications of associated proteins that are aggravated by DM. Plasma CLU, MPO, and PON1 could constitute indicators of HDL dysfunction and contribute to risk stratification in PAD patients.<\/jats:p>","DOI":"10.1002\/biof.1800","type":"journal-article","created":{"date-parts":[[2021,11,6]],"date-time":"2021-11-06T14:48:46Z","timestamp":1636210126000},"page":"454-468","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Clusterin, paraoxonase 1, and myeloperoxidase alterations induce high\u2010density lipoproteins dysfunction and contribute to peripheral artery disease; aggravation by type 2 diabetes mellitus"],"prefix":"10.1002","volume":"48","author":[{"given":"Gabriela M.","family":"Sanda","sequence":"first","affiliation":[{"name":"Lipidomics Department Institute of Cellular Biology and Pathology \u201cNicolae Simionescu\u201d of the Romanian Academy  Bucharest 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