Galectin‐3 aggravates ox‐LDL‐induced endothelial dysfunction through LOX‐1 mediated signaling pathway
Galectin‐3, a biomarker linking oxidative stress and inflammation, participates in different mechanisms related to atherothrombosis, such as inflammation, proliferation, or macrophage chemotaxis. Accumulating evidence indicates that galectin‐3 may also promote atherogenesis through inducing endothel...
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| Veröffentlicht in: | Environmental toxicology 2019-07, Vol.34 (7), p.825-835 |
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| creator | Ou, Hsiu‐Chung Chou, Wan‐Ching Hung, Ching‐Hsia Chu, Pei‐Ming Hsieh, Pei‐Ling Chan, Shih‐Hung Tsai, Kun‐Ling |
| description | Galectin‐3, a biomarker linking oxidative stress and inflammation, participates in different mechanisms related to atherothrombosis, such as inflammation, proliferation, or macrophage chemotaxis. Accumulating evidence indicates that galectin‐3 may also promote atherogenesis through inducing endothelial dysfunction. Lectin‐like oxidized low‐density lipoprotein (oxLDL) receptor‐1 (LOX‐1), a receptor for oxLDL uptake, contributes to oxLDL‐induced endothelial dysfunction. Whether galectin‐3 induces endothelial dysfunction through modulation of LOX‐1‐mediated signaling remains unclear. In the present study, we explored the mechanisms underlying galectin‐3 enhanced cytotoxicity of oxLDL in human umbilical vein endothelial cells (HUVECs) and the role of LOX‐1. Incubation of HUVECs with galectin‐3 increased the expression of LOX‐1 in RNA and protein levels. In addition, the expression of LOX‐1 induced by oxLDL was promoted by galectin‐3. However, pretreatment of LOX‐1 antibody reduced LOX‐1 mRNA expression level in cells with oxLDL plus galectin‐3 incubation. Compared to cells treated with oxLDL alone, reactive oxygen species (ROS) generation via nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation and subsequent activation of p38 mitogen‐activated protein kinases followed by nuclear factor kappa B (NF‐κB) activation and related inflammatory responses including adhesion molecule expression, adhesiveness of monocytic cells, and IL‐8 release were also aggravated in cells treated with galectin‐3 combined with oxLDL. Compared to cells treated with galectin‐3 plus oxLDL group. We found that LOX‐1 antibody mitigated NADPH oxidase activity, p‐38 up‐regulation, NF‐κB activation, and proinflammatory responses in cells treated with galectin‐3 combined with oxLDL. We conclude that galectin‐3 enhances endothelial LOX‐1 expression and propose a new mechanism by which galectin‐3 may promote endothelial dysfunction by inducing inflammation via LOX‐1/ROS/p38/NF‐κB‐mediated signaling pathway. |
| doi_str_mv | 10.1002/tox.22750 |
| format | Article |
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Accumulating evidence indicates that galectin‐3 may also promote atherogenesis through inducing endothelial dysfunction. Lectin‐like oxidized low‐density lipoprotein (oxLDL) receptor‐1 (LOX‐1), a receptor for oxLDL uptake, contributes to oxLDL‐induced endothelial dysfunction. Whether galectin‐3 induces endothelial dysfunction through modulation of LOX‐1‐mediated signaling remains unclear. In the present study, we explored the mechanisms underlying galectin‐3 enhanced cytotoxicity of oxLDL in human umbilical vein endothelial cells (HUVECs) and the role of LOX‐1. Incubation of HUVECs with galectin‐3 increased the expression of LOX‐1 in RNA and protein levels. In addition, the expression of LOX‐1 induced by oxLDL was promoted by galectin‐3. However, pretreatment of LOX‐1 antibody reduced LOX‐1 mRNA expression level in cells with oxLDL plus galectin‐3 incubation. Compared to cells treated with oxLDL alone, reactive oxygen species (ROS) generation via nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation and subsequent activation of p38 mitogen‐activated protein kinases followed by nuclear factor kappa B (NF‐κB) activation and related inflammatory responses including adhesion molecule expression, adhesiveness of monocytic cells, and IL‐8 release were also aggravated in cells treated with galectin‐3 combined with oxLDL. Compared to cells treated with galectin‐3 plus oxLDL group. We found that LOX‐1 antibody mitigated NADPH oxidase activity, p‐38 up‐regulation, NF‐κB activation, and proinflammatory responses in cells treated with galectin‐3 combined with oxLDL. We conclude that galectin‐3 enhances endothelial LOX‐1 expression and propose a new mechanism by which galectin‐3 may promote endothelial dysfunction by inducing inflammation via LOX‐1/ROS/p38/NF‐κB‐mediated signaling pathway.</description><identifier>ISSN: 1520-4081</identifier><identifier>EISSN: 1522-7278</identifier><identifier>DOI: 10.1002/tox.22750</identifier><identifier>PMID: 30963716</identifier><language>eng</language><publisher>Hoboken, USA: John Wiley & Sons, Inc</publisher><subject>Activation ; Antibodies ; Atherogenesis ; Atherosclerosis - chemically induced ; Atherosclerosis - metabolism ; Atherosclerosis - pathology ; Biomarkers ; Cells, Cultured ; Chemotaxis ; Cytotoxicity ; Drug Synergism ; Endothelial cells ; Endothelium, Vascular - drug effects ; Galectin 3 - pharmacology ; galectin‐3 ; Gene expression ; Human Umbilical Vein Endothelial Cells - drug effects ; Human Umbilical Vein Endothelial Cells - physiology ; Humans ; Incubation period ; Inflammation ; Inflammation - chemically induced ; Inflammation - metabolism ; Inflammation - pathology ; Kinases ; Lipoproteins ; Lipoproteins, LDL - toxicity ; Liquid oxygen ; Low density lipoprotein ; LOX‐1 ; Macrophages ; Monocytes ; NAD(P)H oxidase ; NADPH oxidase ; NADPH-diaphorase ; NF-kappa B - metabolism ; Nicotinamide ; Nicotinamide adenine dinucleotide ; Nucleic acids ; Oxidase ; Oxidative stress ; Oxidative Stress - drug effects ; Oxidative Stress - physiology ; p38 Mitogen-Activated Protein Kinases - metabolism ; Phosphates ; Pretreatment ; Proliferation ; Proteins ; Reactive oxygen species ; Reactive Oxygen Species - metabolism ; Receptor density ; Receptors ; RNA ; Scavenger Receptors, Class E - physiology ; Signal transduction ; Signal Transduction - drug effects ; Signaling ; THP-1 Cells ; Toxicity ; Umbilical vein ; Uptake</subject><ispartof>Environmental toxicology, 2019-07, Vol.34 (7), p.825-835</ispartof><rights>2019 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3900-95ed3f22bd85514892aee998c2b2bf45ea77312f500203b4fe304ec1af7bd783</citedby><cites>FETCH-LOGICAL-c3900-95ed3f22bd85514892aee998c2b2bf45ea77312f500203b4fe304ec1af7bd783</cites><orcidid>0000-0002-3814-1453</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Ftox.22750$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Ftox.22750$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30963716$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ou, Hsiu‐Chung</creatorcontrib><creatorcontrib>Chou, Wan‐Ching</creatorcontrib><creatorcontrib>Hung, Ching‐Hsia</creatorcontrib><creatorcontrib>Chu, Pei‐Ming</creatorcontrib><creatorcontrib>Hsieh, Pei‐Ling</creatorcontrib><creatorcontrib>Chan, Shih‐Hung</creatorcontrib><creatorcontrib>Tsai, Kun‐Ling</creatorcontrib><title>Galectin‐3 aggravates ox‐LDL‐induced endothelial dysfunction through LOX‐1 mediated signaling pathway</title><title>Environmental toxicology</title><addtitle>Environ Toxicol</addtitle><description>Galectin‐3, a biomarker linking oxidative stress and inflammation, participates in different mechanisms related to atherothrombosis, such as inflammation, proliferation, or macrophage chemotaxis. Accumulating evidence indicates that galectin‐3 may also promote atherogenesis through inducing endothelial dysfunction. Lectin‐like oxidized low‐density lipoprotein (oxLDL) receptor‐1 (LOX‐1), a receptor for oxLDL uptake, contributes to oxLDL‐induced endothelial dysfunction. Whether galectin‐3 induces endothelial dysfunction through modulation of LOX‐1‐mediated signaling remains unclear. In the present study, we explored the mechanisms underlying galectin‐3 enhanced cytotoxicity of oxLDL in human umbilical vein endothelial cells (HUVECs) and the role of LOX‐1. Incubation of HUVECs with galectin‐3 increased the expression of LOX‐1 in RNA and protein levels. In addition, the expression of LOX‐1 induced by oxLDL was promoted by galectin‐3. However, pretreatment of LOX‐1 antibody reduced LOX‐1 mRNA expression level in cells with oxLDL plus galectin‐3 incubation. Compared to cells treated with oxLDL alone, reactive oxygen species (ROS) generation via nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation and subsequent activation of p38 mitogen‐activated protein kinases followed by nuclear factor kappa B (NF‐κB) activation and related inflammatory responses including adhesion molecule expression, adhesiveness of monocytic cells, and IL‐8 release were also aggravated in cells treated with galectin‐3 combined with oxLDL. Compared to cells treated with galectin‐3 plus oxLDL group. We found that LOX‐1 antibody mitigated NADPH oxidase activity, p‐38 up‐regulation, NF‐κB activation, and proinflammatory responses in cells treated with galectin‐3 combined with oxLDL. We conclude that galectin‐3 enhances endothelial LOX‐1 expression and propose a new mechanism by which galectin‐3 may promote endothelial dysfunction by inducing inflammation via LOX‐1/ROS/p38/NF‐κB‐mediated signaling pathway.</description><subject>Activation</subject><subject>Antibodies</subject><subject>Atherogenesis</subject><subject>Atherosclerosis - chemically induced</subject><subject>Atherosclerosis - metabolism</subject><subject>Atherosclerosis - pathology</subject><subject>Biomarkers</subject><subject>Cells, Cultured</subject><subject>Chemotaxis</subject><subject>Cytotoxicity</subject><subject>Drug Synergism</subject><subject>Endothelial cells</subject><subject>Endothelium, Vascular - drug effects</subject><subject>Galectin 3 - pharmacology</subject><subject>galectin‐3</subject><subject>Gene expression</subject><subject>Human Umbilical Vein Endothelial Cells - drug effects</subject><subject>Human Umbilical Vein Endothelial Cells - physiology</subject><subject>Humans</subject><subject>Incubation period</subject><subject>Inflammation</subject><subject>Inflammation - chemically induced</subject><subject>Inflammation - metabolism</subject><subject>Inflammation - pathology</subject><subject>Kinases</subject><subject>Lipoproteins</subject><subject>Lipoproteins, LDL - toxicity</subject><subject>Liquid oxygen</subject><subject>Low density lipoprotein</subject><subject>LOX‐1</subject><subject>Macrophages</subject><subject>Monocytes</subject><subject>NAD(P)H oxidase</subject><subject>NADPH oxidase</subject><subject>NADPH-diaphorase</subject><subject>NF-kappa B - metabolism</subject><subject>Nicotinamide</subject><subject>Nicotinamide adenine dinucleotide</subject><subject>Nucleic acids</subject><subject>Oxidase</subject><subject>Oxidative stress</subject><subject>Oxidative Stress - drug effects</subject><subject>Oxidative Stress - physiology</subject><subject>p38 Mitogen-Activated Protein Kinases - metabolism</subject><subject>Phosphates</subject><subject>Pretreatment</subject><subject>Proliferation</subject><subject>Proteins</subject><subject>Reactive oxygen species</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>Receptor density</subject><subject>Receptors</subject><subject>RNA</subject><subject>Scavenger Receptors, Class E - physiology</subject><subject>Signal transduction</subject><subject>Signal Transduction - drug effects</subject><subject>Signaling</subject><subject>THP-1 Cells</subject><subject>Toxicity</subject><subject>Umbilical vein</subject><subject>Uptake</subject><issn>1520-4081</issn><issn>1522-7278</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kbtOwzAUhi0E4lIYeAFkiQWGUF-SOBlRgYIUqUuHbpETnyRGaVziBMjGI_CMPAnuBQYkFp-jo8-f7PMjdE7JDSWEjTvzfsOYCMgeOqYBY55gItrf9MTzSUSP0Im1z4SQOAzCQ3TEXcMFDY_RcipryDvdfH18cizLspWvsgOLzbubJHeJO3Wj-hwUhkaZroJayxqrwRZ94y6aBndVa_qywsls4WiKl6C0cyhsddnIWjclXsmuepPDKTooZG3hbFdHaP5wP588esls-jS5Tbycx4R4cQCKF4xlKgoC6kcxkwBxHOUsY1nhByCF4JQVgfs84ZlfACc-5FQWIlMi4iN0tdWuWvPSg-3SpbY51LVswPQ2ZYyEjDkvd-jlH_TZ9K179ZriPudEhGvqekvlrbG2hSJdtXop2yGlJF1HkLoI0k0Ejr3YGfvMbeKX_Nm5A8Zb4E3XMPxvSuezxVb5DUwDlC8</recordid><startdate>201907</startdate><enddate>201907</enddate><creator>Ou, Hsiu‐Chung</creator><creator>Chou, Wan‐Ching</creator><creator>Hung, Ching‐Hsia</creator><creator>Chu, Pei‐Ming</creator><creator>Hsieh, Pei‐Ling</creator><creator>Chan, Shih‐Hung</creator><creator>Tsai, Kun‐Ling</creator><general>John Wiley & Sons, Inc</general><general>Wiley Subscription Services, Inc</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>7QH</scope><scope>7ST</scope><scope>7TN</scope><scope>7U7</scope><scope>7UA</scope><scope>C1K</scope><scope>F1W</scope><scope>H97</scope><scope>K9.</scope><scope>L.G</scope><scope>M7N</scope><scope>SOI</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-3814-1453</orcidid></search><sort><creationdate>201907</creationdate><title>Galectin‐3 aggravates ox‐LDL‐induced endothelial dysfunction through LOX‐1 mediated signaling pathway</title><author>Ou, Hsiu‐Chung ; Chou, Wan‐Ching ; Hung, Ching‐Hsia ; Chu, Pei‐Ming ; Hsieh, Pei‐Ling ; Chan, Shih‐Hung ; Tsai, Kun‐Ling</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3900-95ed3f22bd85514892aee998c2b2bf45ea77312f500203b4fe304ec1af7bd783</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Activation</topic><topic>Antibodies</topic><topic>Atherogenesis</topic><topic>Atherosclerosis - chemically induced</topic><topic>Atherosclerosis - metabolism</topic><topic>Atherosclerosis - pathology</topic><topic>Biomarkers</topic><topic>Cells, Cultured</topic><topic>Chemotaxis</topic><topic>Cytotoxicity</topic><topic>Drug Synergism</topic><topic>Endothelial cells</topic><topic>Endothelium, Vascular - drug effects</topic><topic>Galectin 3 - pharmacology</topic><topic>galectin‐3</topic><topic>Gene expression</topic><topic>Human Umbilical Vein Endothelial Cells - drug effects</topic><topic>Human Umbilical Vein Endothelial Cells - physiology</topic><topic>Humans</topic><topic>Incubation period</topic><topic>Inflammation</topic><topic>Inflammation - chemically induced</topic><topic>Inflammation - metabolism</topic><topic>Inflammation - pathology</topic><topic>Kinases</topic><topic>Lipoproteins</topic><topic>Lipoproteins, LDL - toxicity</topic><topic>Liquid oxygen</topic><topic>Low density lipoprotein</topic><topic>LOX‐1</topic><topic>Macrophages</topic><topic>Monocytes</topic><topic>NAD(P)H oxidase</topic><topic>NADPH oxidase</topic><topic>NADPH-diaphorase</topic><topic>NF-kappa B - metabolism</topic><topic>Nicotinamide</topic><topic>Nicotinamide adenine dinucleotide</topic><topic>Nucleic acids</topic><topic>Oxidase</topic><topic>Oxidative stress</topic><topic>Oxidative Stress - drug effects</topic><topic>Oxidative Stress - physiology</topic><topic>p38 Mitogen-Activated Protein Kinases - metabolism</topic><topic>Phosphates</topic><topic>Pretreatment</topic><topic>Proliferation</topic><topic>Proteins</topic><topic>Reactive oxygen species</topic><topic>Reactive Oxygen Species - metabolism</topic><topic>Receptor density</topic><topic>Receptors</topic><topic>RNA</topic><topic>Scavenger Receptors, Class E - physiology</topic><topic>Signal transduction</topic><topic>Signal Transduction - drug effects</topic><topic>Signaling</topic><topic>THP-1 Cells</topic><topic>Toxicity</topic><topic>Umbilical vein</topic><topic>Uptake</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ou, Hsiu‐Chung</creatorcontrib><creatorcontrib>Chou, Wan‐Ching</creatorcontrib><creatorcontrib>Hung, Ching‐Hsia</creatorcontrib><creatorcontrib>Chu, Pei‐Ming</creatorcontrib><creatorcontrib>Hsieh, Pei‐Ling</creatorcontrib><creatorcontrib>Chan, Shih‐Hung</creatorcontrib><creatorcontrib>Tsai, Kun‐Ling</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Aqualine</collection><collection>Environment Abstracts</collection><collection>Oceanic Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Water Resources Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ASFA: Aquatic Sciences and Fisheries Abstracts</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) 3: Aquatic Pollution & Environmental Quality</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) Professional</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Environment Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Environmental toxicology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ou, Hsiu‐Chung</au><au>Chou, Wan‐Ching</au><au>Hung, Ching‐Hsia</au><au>Chu, Pei‐Ming</au><au>Hsieh, Pei‐Ling</au><au>Chan, Shih‐Hung</au><au>Tsai, Kun‐Ling</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Galectin‐3 aggravates ox‐LDL‐induced endothelial dysfunction through LOX‐1 mediated signaling pathway</atitle><jtitle>Environmental toxicology</jtitle><addtitle>Environ Toxicol</addtitle><date>2019-07</date><risdate>2019</risdate><volume>34</volume><issue>7</issue><spage>825</spage><epage>835</epage><pages>825-835</pages><issn>1520-4081</issn><eissn>1522-7278</eissn><abstract>Galectin‐3, a biomarker linking oxidative stress and inflammation, participates in different mechanisms related to atherothrombosis, such as inflammation, proliferation, or macrophage chemotaxis. Accumulating evidence indicates that galectin‐3 may also promote atherogenesis through inducing endothelial dysfunction. Lectin‐like oxidized low‐density lipoprotein (oxLDL) receptor‐1 (LOX‐1), a receptor for oxLDL uptake, contributes to oxLDL‐induced endothelial dysfunction. Whether galectin‐3 induces endothelial dysfunction through modulation of LOX‐1‐mediated signaling remains unclear. In the present study, we explored the mechanisms underlying galectin‐3 enhanced cytotoxicity of oxLDL in human umbilical vein endothelial cells (HUVECs) and the role of LOX‐1. Incubation of HUVECs with galectin‐3 increased the expression of LOX‐1 in RNA and protein levels. In addition, the expression of LOX‐1 induced by oxLDL was promoted by galectin‐3. However, pretreatment of LOX‐1 antibody reduced LOX‐1 mRNA expression level in cells with oxLDL plus galectin‐3 incubation. Compared to cells treated with oxLDL alone, reactive oxygen species (ROS) generation via nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation and subsequent activation of p38 mitogen‐activated protein kinases followed by nuclear factor kappa B (NF‐κB) activation and related inflammatory responses including adhesion molecule expression, adhesiveness of monocytic cells, and IL‐8 release were also aggravated in cells treated with galectin‐3 combined with oxLDL. Compared to cells treated with galectin‐3 plus oxLDL group. We found that LOX‐1 antibody mitigated NADPH oxidase activity, p‐38 up‐regulation, NF‐κB activation, and proinflammatory responses in cells treated with galectin‐3 combined with oxLDL. We conclude that galectin‐3 enhances endothelial LOX‐1 expression and propose a new mechanism by which galectin‐3 may promote endothelial dysfunction by inducing inflammation via LOX‐1/ROS/p38/NF‐κB‐mediated signaling pathway.</abstract><cop>Hoboken, USA</cop><pub>John Wiley & Sons, Inc</pub><pmid>30963716</pmid><doi>10.1002/tox.22750</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-3814-1453</orcidid></addata></record> |
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| subjects | Activation Antibodies Atherogenesis Atherosclerosis - chemically induced Atherosclerosis - metabolism Atherosclerosis - pathology Biomarkers Cells, Cultured Chemotaxis Cytotoxicity Drug Synergism Endothelial cells Endothelium, Vascular - drug effects Galectin 3 - pharmacology galectin‐3 Gene expression Human Umbilical Vein Endothelial Cells - drug effects Human Umbilical Vein Endothelial Cells - physiology Humans Incubation period Inflammation Inflammation - chemically induced Inflammation - metabolism Inflammation - pathology Kinases Lipoproteins Lipoproteins, LDL - toxicity Liquid oxygen Low density lipoprotein LOX‐1 Macrophages Monocytes NAD(P)H oxidase NADPH oxidase NADPH-diaphorase NF-kappa B - metabolism Nicotinamide Nicotinamide adenine dinucleotide Nucleic acids Oxidase Oxidative stress Oxidative Stress - drug effects Oxidative Stress - physiology p38 Mitogen-Activated Protein Kinases - metabolism Phosphates Pretreatment Proliferation Proteins Reactive oxygen species Reactive Oxygen Species - metabolism Receptor density Receptors RNA Scavenger Receptors, Class E - physiology Signal transduction Signal Transduction - drug effects Signaling THP-1 Cells Toxicity Umbilical vein Uptake |
| title | Galectin‐3 aggravates ox‐LDL‐induced endothelial dysfunction through LOX‐1 mediated signaling pathway |
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