Potential of dapagliflozin to prevent vascular remodeling in the rat carotid artery following balloon injury
Sodium-glucose co-transporter 2 (SGLT2) inhibitors have been shown to reduce the risk of cardiovascular events independently of glycemic control. However, the possibility that SGLT2 inhibitors improve vascular restenosis is unknown. The aim of this study was to examine whether dapagliflozin could pr...
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| creator | Matsushita, Kensuke Sato, Chisato Bruckert, Christophe Gong, DalSeong Amissi, Said Hmadeh, Sandy Fakih, Walaa Remila, Lamia Lessinger, Jean-Marc Auger, Cyril Jesel, Laurence Ohlmann, Patrick Kauffenstein, Gilles Schini-Kerth, Valérie B. Morel, Olivier |
| description | Sodium-glucose co-transporter 2 (SGLT2) inhibitors have been shown to reduce the risk of cardiovascular events independently of glycemic control. However, the possibility that SGLT2 inhibitors improve vascular restenosis is unknown. The aim of this study was to examine whether dapagliflozin could prevent neointima thickening following balloon injury and, if so, to determine the underlying mechanisms.
Saline, dapagliflozin (1.5 mg/kg/day), or losartan (30 mg/kg/day) was administered orally for five weeks to male Wistar rats. Balloon injury of the left carotid artery was performed a week after starting the treatment and rats were sacrificed 4 weeks later. The extent of neointima was assessed by histomorphometric and immunofluorescence staining analyses. Vascular reactivity was assessed on injured and non-injured carotid artery rings, changes of target factors by immunofluorescence, RT-qPCR, and histochemistry.
Dapagliflozin and losartan treatments reduced neointima thickening by 32 % and 27 %, respectively. Blunted contractile responses to phenylephrine and relaxations to acetylcholine and down-regulation of eNOS were observed in the injured arteries. RT-qPCR investigations indicated an increased in gene expression of inflammatory (IL-1beta, VCAM-1), oxidative (p47phox, p22phox) and fibrotic (TGF-beta1) markers in the injured carotid. While these changes were not affected by dapagliflozin, increased levels of AT1R and NTPDase1 (CD39) and decreased levels of ENPP1 were observed in the restenotic carotid artery of the dapagliflozin group.
Dapagliflozin effectively reduced neointimal thickening. The present data suggest that dapagliflozin prevents restenosis through interfering with angiotensin and/or extracellular nucleotides signaling. SGLT2 represents potential new target for limiting vascular restenosis.
[Display omitted]
•There are scarcely any pharmacological treatments demonstrating beneficial effects on in-stent restenosis.•In this study, dapagliflozin prevented rat restenosis through interfering with angiotensin/extracellular nucleotides.•Future clinical trials are warranted to confirm the anti-proliferative effects of SGLT2 inhibitors in patients. |
| doi_str_mv | 10.1016/j.atherosclerosis.2024.117595 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_hal_p</sourceid><recordid>TN_cdi_hal_primary_oai_HAL_hal_04670661v1</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0021915024001552</els_id><sourcerecordid>3068758502</sourcerecordid><originalsourceid>FETCH-LOGICAL-c478t-96c924e83424ad23be2df423200c021383ca7be4021eba7223d6169abb2c83713</originalsourceid><addsrcrecordid>eNqNkU1v1DAQQC1ERbeFv4B8QYJDFn8ldg4cqoq2SCvRA5wtx5l0vfLGi-1stfz6OkrbAycu9mj8Zkaeh9AnStaU0Obrbm3yFmJI1s-nS2tGmFhTKuu2foNWVMm2okKJt2hFCKNVS2tyji5S2hFChKTqHTrnqlBcyRXy9yHDmJ3xOAy4Nwfz4N3gw1834hzwIcKxPOOjSXbyJuII-9CDd-MDnokt4GgytiaG7HpsYoZ4wkPwPjzOTGdKFMbC7qZ4eo_OBuMTfHi-L9Hvm--_ru-qzc_bH9dXm8oKqXLVNrZlAhQXTJie8Q5YPwjGGSG2_Igrbo3sQJQYOiMZ431Dm9Z0HbOKS8ov0Zel79Z4fYhub-JJB-P03dVGzzkiGkmahh5n9vPCHmL4M0HKeu-SBe_NCGFKmpNGyVrVhBX024LasvgUYXjtTYme5eid_keOnuXoRU6p__g8aur20L9Wv9gowO0CQFnO0UHUyToYLfQugs26D-4_Rz0Bf0CrMQ</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3068758502</pqid></control><display><type>article</type><title>Potential of dapagliflozin to prevent vascular remodeling in the rat carotid artery following balloon injury</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals</source><creator>Matsushita, Kensuke ; Sato, Chisato ; Bruckert, Christophe ; Gong, DalSeong ; Amissi, Said ; Hmadeh, Sandy ; Fakih, Walaa ; Remila, Lamia ; Lessinger, Jean-Marc ; Auger, Cyril ; Jesel, Laurence ; Ohlmann, Patrick ; Kauffenstein, Gilles ; Schini-Kerth, Valérie B. ; Morel, Olivier</creator><creatorcontrib>Matsushita, Kensuke ; Sato, Chisato ; Bruckert, Christophe ; Gong, DalSeong ; Amissi, Said ; Hmadeh, Sandy ; Fakih, Walaa ; Remila, Lamia ; Lessinger, Jean-Marc ; Auger, Cyril ; Jesel, Laurence ; Ohlmann, Patrick ; Kauffenstein, Gilles ; Schini-Kerth, Valérie B. ; Morel, Olivier</creatorcontrib><description>Sodium-glucose co-transporter 2 (SGLT2) inhibitors have been shown to reduce the risk of cardiovascular events independently of glycemic control. However, the possibility that SGLT2 inhibitors improve vascular restenosis is unknown. The aim of this study was to examine whether dapagliflozin could prevent neointima thickening following balloon injury and, if so, to determine the underlying mechanisms.
Saline, dapagliflozin (1.5 mg/kg/day), or losartan (30 mg/kg/day) was administered orally for five weeks to male Wistar rats. Balloon injury of the left carotid artery was performed a week after starting the treatment and rats were sacrificed 4 weeks later. The extent of neointima was assessed by histomorphometric and immunofluorescence staining analyses. Vascular reactivity was assessed on injured and non-injured carotid artery rings, changes of target factors by immunofluorescence, RT-qPCR, and histochemistry.
Dapagliflozin and losartan treatments reduced neointima thickening by 32 % and 27 %, respectively. Blunted contractile responses to phenylephrine and relaxations to acetylcholine and down-regulation of eNOS were observed in the injured arteries. RT-qPCR investigations indicated an increased in gene expression of inflammatory (IL-1beta, VCAM-1), oxidative (p47phox, p22phox) and fibrotic (TGF-beta1) markers in the injured carotid. While these changes were not affected by dapagliflozin, increased levels of AT1R and NTPDase1 (CD39) and decreased levels of ENPP1 were observed in the restenotic carotid artery of the dapagliflozin group.
Dapagliflozin effectively reduced neointimal thickening. The present data suggest that dapagliflozin prevents restenosis through interfering with angiotensin and/or extracellular nucleotides signaling. SGLT2 represents potential new target for limiting vascular restenosis.
[Display omitted]
•There are scarcely any pharmacological treatments demonstrating beneficial effects on in-stent restenosis.•In this study, dapagliflozin prevented rat restenosis through interfering with angiotensin/extracellular nucleotides.•Future clinical trials are warranted to confirm the anti-proliferative effects of SGLT2 inhibitors in patients.</description><identifier>ISSN: 0021-9150</identifier><identifier>ISSN: 1879-1484</identifier><identifier>EISSN: 1879-1484</identifier><identifier>DOI: 10.1016/j.atherosclerosis.2024.117595</identifier><identifier>PMID: 38879387</identifier><language>eng</language><publisher>Ireland: Elsevier B.V</publisher><subject>Angioplasty, Balloon - adverse effects ; Angiotensin ; Animals ; Benzhydryl Compounds - pharmacology ; Cardiology and cardiovascular system ; Carotid Arteries - drug effects ; Carotid Arteries - metabolism ; Carotid Arteries - pathology ; Carotid Artery Injuries - drug therapy ; Carotid Artery Injuries - metabolism ; Carotid Artery Injuries - pathology ; Dapagliflozin ; Disease Models, Animal ; Endothelial dysfunction ; Glucosides - pharmacology ; Human health and pathology ; Life Sciences ; Losartan - pharmacology ; Male ; Neointima ; Neointima formation ; Nitric Oxide Synthase Type III - metabolism ; Oxidative Stress - drug effects ; Pharmaceutical sciences ; Pharmacology ; Purinergic signaling ; Rats ; Rats, Wistar ; SGLT2 ; Sodium-Glucose Transporter 2 Inhibitors - pharmacology ; Transforming Growth Factor beta1 - metabolism ; Vascular Remodeling - drug effects</subject><ispartof>Atherosclerosis, 2024-10, Vol.397, p.117595, Article 117595</ispartof><rights>2024 The Authors</rights><rights>Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c478t-96c924e83424ad23be2df423200c021383ca7be4021eba7223d6169abb2c83713</citedby><cites>FETCH-LOGICAL-c478t-96c924e83424ad23be2df423200c021383ca7be4021eba7223d6169abb2c83713</cites><orcidid>0000-0002-3722-2921 ; 0000-0002-1998-499X ; 0000-0003-4742-3740 ; 0000-0001-9997-9287 ; 0000-0002-7295-3041 ; 0000-0002-8021-2737 ; 0000-0003-0695-3841 ; 0000-0003-4994-8305 ; 0000-0003-0423-259X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0021915024001552$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65534</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38879387$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-04670661$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Matsushita, Kensuke</creatorcontrib><creatorcontrib>Sato, Chisato</creatorcontrib><creatorcontrib>Bruckert, Christophe</creatorcontrib><creatorcontrib>Gong, DalSeong</creatorcontrib><creatorcontrib>Amissi, Said</creatorcontrib><creatorcontrib>Hmadeh, Sandy</creatorcontrib><creatorcontrib>Fakih, Walaa</creatorcontrib><creatorcontrib>Remila, Lamia</creatorcontrib><creatorcontrib>Lessinger, Jean-Marc</creatorcontrib><creatorcontrib>Auger, Cyril</creatorcontrib><creatorcontrib>Jesel, Laurence</creatorcontrib><creatorcontrib>Ohlmann, Patrick</creatorcontrib><creatorcontrib>Kauffenstein, Gilles</creatorcontrib><creatorcontrib>Schini-Kerth, Valérie B.</creatorcontrib><creatorcontrib>Morel, Olivier</creatorcontrib><title>Potential of dapagliflozin to prevent vascular remodeling in the rat carotid artery following balloon injury</title><title>Atherosclerosis</title><addtitle>Atherosclerosis</addtitle><description>Sodium-glucose co-transporter 2 (SGLT2) inhibitors have been shown to reduce the risk of cardiovascular events independently of glycemic control. However, the possibility that SGLT2 inhibitors improve vascular restenosis is unknown. The aim of this study was to examine whether dapagliflozin could prevent neointima thickening following balloon injury and, if so, to determine the underlying mechanisms.
Saline, dapagliflozin (1.5 mg/kg/day), or losartan (30 mg/kg/day) was administered orally for five weeks to male Wistar rats. Balloon injury of the left carotid artery was performed a week after starting the treatment and rats were sacrificed 4 weeks later. The extent of neointima was assessed by histomorphometric and immunofluorescence staining analyses. Vascular reactivity was assessed on injured and non-injured carotid artery rings, changes of target factors by immunofluorescence, RT-qPCR, and histochemistry.
Dapagliflozin and losartan treatments reduced neointima thickening by 32 % and 27 %, respectively. Blunted contractile responses to phenylephrine and relaxations to acetylcholine and down-regulation of eNOS were observed in the injured arteries. RT-qPCR investigations indicated an increased in gene expression of inflammatory (IL-1beta, VCAM-1), oxidative (p47phox, p22phox) and fibrotic (TGF-beta1) markers in the injured carotid. While these changes were not affected by dapagliflozin, increased levels of AT1R and NTPDase1 (CD39) and decreased levels of ENPP1 were observed in the restenotic carotid artery of the dapagliflozin group.
Dapagliflozin effectively reduced neointimal thickening. The present data suggest that dapagliflozin prevents restenosis through interfering with angiotensin and/or extracellular nucleotides signaling. SGLT2 represents potential new target for limiting vascular restenosis.
[Display omitted]
•There are scarcely any pharmacological treatments demonstrating beneficial effects on in-stent restenosis.•In this study, dapagliflozin prevented rat restenosis through interfering with angiotensin/extracellular nucleotides.•Future clinical trials are warranted to confirm the anti-proliferative effects of SGLT2 inhibitors in patients.</description><subject>Angioplasty, Balloon - adverse effects</subject><subject>Angiotensin</subject><subject>Animals</subject><subject>Benzhydryl Compounds - pharmacology</subject><subject>Cardiology and cardiovascular system</subject><subject>Carotid Arteries - drug effects</subject><subject>Carotid Arteries - metabolism</subject><subject>Carotid Arteries - pathology</subject><subject>Carotid Artery Injuries - drug therapy</subject><subject>Carotid Artery Injuries - metabolism</subject><subject>Carotid Artery Injuries - pathology</subject><subject>Dapagliflozin</subject><subject>Disease Models, Animal</subject><subject>Endothelial dysfunction</subject><subject>Glucosides - pharmacology</subject><subject>Human health and pathology</subject><subject>Life Sciences</subject><subject>Losartan - pharmacology</subject><subject>Male</subject><subject>Neointima</subject><subject>Neointima formation</subject><subject>Nitric Oxide Synthase Type III - metabolism</subject><subject>Oxidative Stress - drug effects</subject><subject>Pharmaceutical sciences</subject><subject>Pharmacology</subject><subject>Purinergic signaling</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>SGLT2</subject><subject>Sodium-Glucose Transporter 2 Inhibitors - pharmacology</subject><subject>Transforming Growth Factor beta1 - metabolism</subject><subject>Vascular Remodeling - drug effects</subject><issn>0021-9150</issn><issn>1879-1484</issn><issn>1879-1484</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkU1v1DAQQC1ERbeFv4B8QYJDFn8ldg4cqoq2SCvRA5wtx5l0vfLGi-1stfz6OkrbAycu9mj8Zkaeh9AnStaU0Obrbm3yFmJI1s-nS2tGmFhTKuu2foNWVMm2okKJt2hFCKNVS2tyji5S2hFChKTqHTrnqlBcyRXy9yHDmJ3xOAy4Nwfz4N3gw1834hzwIcKxPOOjSXbyJuII-9CDd-MDnokt4GgytiaG7HpsYoZ4wkPwPjzOTGdKFMbC7qZ4eo_OBuMTfHi-L9Hvm--_ru-qzc_bH9dXm8oKqXLVNrZlAhQXTJie8Q5YPwjGGSG2_Igrbo3sQJQYOiMZ431Dm9Z0HbOKS8ov0Zel79Z4fYhub-JJB-P03dVGzzkiGkmahh5n9vPCHmL4M0HKeu-SBe_NCGFKmpNGyVrVhBX024LasvgUYXjtTYme5eid_keOnuXoRU6p__g8aur20L9Wv9gowO0CQFnO0UHUyToYLfQugs26D-4_Rz0Bf0CrMQ</recordid><startdate>20241001</startdate><enddate>20241001</enddate><creator>Matsushita, Kensuke</creator><creator>Sato, Chisato</creator><creator>Bruckert, Christophe</creator><creator>Gong, DalSeong</creator><creator>Amissi, Said</creator><creator>Hmadeh, Sandy</creator><creator>Fakih, Walaa</creator><creator>Remila, Lamia</creator><creator>Lessinger, Jean-Marc</creator><creator>Auger, Cyril</creator><creator>Jesel, Laurence</creator><creator>Ohlmann, Patrick</creator><creator>Kauffenstein, Gilles</creator><creator>Schini-Kerth, Valérie B.</creator><creator>Morel, Olivier</creator><general>Elsevier B.V</general><general>Elsevier</general><scope>6I.</scope><scope>AAFTH</scope><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>7X8</scope><scope>1XC</scope><scope>VOOES</scope><orcidid>https://orcid.org/0000-0002-3722-2921</orcidid><orcidid>https://orcid.org/0000-0002-1998-499X</orcidid><orcidid>https://orcid.org/0000-0003-4742-3740</orcidid><orcidid>https://orcid.org/0000-0001-9997-9287</orcidid><orcidid>https://orcid.org/0000-0002-7295-3041</orcidid><orcidid>https://orcid.org/0000-0002-8021-2737</orcidid><orcidid>https://orcid.org/0000-0003-0695-3841</orcidid><orcidid>https://orcid.org/0000-0003-4994-8305</orcidid><orcidid>https://orcid.org/0000-0003-0423-259X</orcidid></search><sort><creationdate>20241001</creationdate><title>Potential of dapagliflozin to prevent vascular remodeling in the rat carotid artery following balloon injury</title><author>Matsushita, Kensuke ; Sato, Chisato ; Bruckert, Christophe ; Gong, DalSeong ; Amissi, Said ; Hmadeh, Sandy ; Fakih, Walaa ; Remila, Lamia ; Lessinger, Jean-Marc ; Auger, Cyril ; Jesel, Laurence ; Ohlmann, Patrick ; Kauffenstein, Gilles ; Schini-Kerth, Valérie B. ; Morel, Olivier</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c478t-96c924e83424ad23be2df423200c021383ca7be4021eba7223d6169abb2c83713</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Angioplasty, Balloon - adverse effects</topic><topic>Angiotensin</topic><topic>Animals</topic><topic>Benzhydryl Compounds - pharmacology</topic><topic>Cardiology and cardiovascular system</topic><topic>Carotid Arteries - drug effects</topic><topic>Carotid Arteries - metabolism</topic><topic>Carotid Arteries - pathology</topic><topic>Carotid Artery Injuries - drug therapy</topic><topic>Carotid Artery Injuries - metabolism</topic><topic>Carotid Artery Injuries - pathology</topic><topic>Dapagliflozin</topic><topic>Disease Models, Animal</topic><topic>Endothelial dysfunction</topic><topic>Glucosides - pharmacology</topic><topic>Human health and pathology</topic><topic>Life Sciences</topic><topic>Losartan - pharmacology</topic><topic>Male</topic><topic>Neointima</topic><topic>Neointima formation</topic><topic>Nitric Oxide Synthase Type III - metabolism</topic><topic>Oxidative Stress - drug effects</topic><topic>Pharmaceutical sciences</topic><topic>Pharmacology</topic><topic>Purinergic signaling</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>SGLT2</topic><topic>Sodium-Glucose Transporter 2 Inhibitors - pharmacology</topic><topic>Transforming Growth Factor beta1 - metabolism</topic><topic>Vascular Remodeling - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Matsushita, Kensuke</creatorcontrib><creatorcontrib>Sato, Chisato</creatorcontrib><creatorcontrib>Bruckert, Christophe</creatorcontrib><creatorcontrib>Gong, DalSeong</creatorcontrib><creatorcontrib>Amissi, Said</creatorcontrib><creatorcontrib>Hmadeh, Sandy</creatorcontrib><creatorcontrib>Fakih, Walaa</creatorcontrib><creatorcontrib>Remila, Lamia</creatorcontrib><creatorcontrib>Lessinger, Jean-Marc</creatorcontrib><creatorcontrib>Auger, Cyril</creatorcontrib><creatorcontrib>Jesel, Laurence</creatorcontrib><creatorcontrib>Ohlmann, Patrick</creatorcontrib><creatorcontrib>Kauffenstein, Gilles</creatorcontrib><creatorcontrib>Schini-Kerth, Valérie B.</creatorcontrib><creatorcontrib>Morel, Olivier</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><collection>Hyper Article en Ligne (HAL) (Open Access)</collection><jtitle>Atherosclerosis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Matsushita, Kensuke</au><au>Sato, Chisato</au><au>Bruckert, Christophe</au><au>Gong, DalSeong</au><au>Amissi, Said</au><au>Hmadeh, Sandy</au><au>Fakih, Walaa</au><au>Remila, Lamia</au><au>Lessinger, Jean-Marc</au><au>Auger, Cyril</au><au>Jesel, Laurence</au><au>Ohlmann, Patrick</au><au>Kauffenstein, Gilles</au><au>Schini-Kerth, Valérie B.</au><au>Morel, Olivier</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Potential of dapagliflozin to prevent vascular remodeling in the rat carotid artery following balloon injury</atitle><jtitle>Atherosclerosis</jtitle><addtitle>Atherosclerosis</addtitle><date>2024-10-01</date><risdate>2024</risdate><volume>397</volume><spage>117595</spage><pages>117595-</pages><artnum>117595</artnum><issn>0021-9150</issn><issn>1879-1484</issn><eissn>1879-1484</eissn><abstract>Sodium-glucose co-transporter 2 (SGLT2) inhibitors have been shown to reduce the risk of cardiovascular events independently of glycemic control. However, the possibility that SGLT2 inhibitors improve vascular restenosis is unknown. The aim of this study was to examine whether dapagliflozin could prevent neointima thickening following balloon injury and, if so, to determine the underlying mechanisms.
Saline, dapagliflozin (1.5 mg/kg/day), or losartan (30 mg/kg/day) was administered orally for five weeks to male Wistar rats. Balloon injury of the left carotid artery was performed a week after starting the treatment and rats were sacrificed 4 weeks later. The extent of neointima was assessed by histomorphometric and immunofluorescence staining analyses. Vascular reactivity was assessed on injured and non-injured carotid artery rings, changes of target factors by immunofluorescence, RT-qPCR, and histochemistry.
Dapagliflozin and losartan treatments reduced neointima thickening by 32 % and 27 %, respectively. Blunted contractile responses to phenylephrine and relaxations to acetylcholine and down-regulation of eNOS were observed in the injured arteries. RT-qPCR investigations indicated an increased in gene expression of inflammatory (IL-1beta, VCAM-1), oxidative (p47phox, p22phox) and fibrotic (TGF-beta1) markers in the injured carotid. While these changes were not affected by dapagliflozin, increased levels of AT1R and NTPDase1 (CD39) and decreased levels of ENPP1 were observed in the restenotic carotid artery of the dapagliflozin group.
Dapagliflozin effectively reduced neointimal thickening. The present data suggest that dapagliflozin prevents restenosis through interfering with angiotensin and/or extracellular nucleotides signaling. SGLT2 represents potential new target for limiting vascular restenosis.
[Display omitted]
•There are scarcely any pharmacological treatments demonstrating beneficial effects on in-stent restenosis.•In this study, dapagliflozin prevented rat restenosis through interfering with angiotensin/extracellular nucleotides.•Future clinical trials are warranted to confirm the anti-proliferative effects of SGLT2 inhibitors in patients.</abstract><cop>Ireland</cop><pub>Elsevier B.V</pub><pmid>38879387</pmid><doi>10.1016/j.atherosclerosis.2024.117595</doi><orcidid>https://orcid.org/0000-0002-3722-2921</orcidid><orcidid>https://orcid.org/0000-0002-1998-499X</orcidid><orcidid>https://orcid.org/0000-0003-4742-3740</orcidid><orcidid>https://orcid.org/0000-0001-9997-9287</orcidid><orcidid>https://orcid.org/0000-0002-7295-3041</orcidid><orcidid>https://orcid.org/0000-0002-8021-2737</orcidid><orcidid>https://orcid.org/0000-0003-0695-3841</orcidid><orcidid>https://orcid.org/0000-0003-4994-8305</orcidid><orcidid>https://orcid.org/0000-0003-0423-259X</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0021-9150 |
| ispartof | Atherosclerosis, 2024-10, Vol.397, p.117595, Article 117595 |
| issn | 0021-9150 1879-1484 1879-1484 |
| language | eng |
| recordid | cdi_hal_primary_oai_HAL_hal_04670661v1 |
| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Angioplasty, Balloon - adverse effects Angiotensin Animals Benzhydryl Compounds - pharmacology Cardiology and cardiovascular system Carotid Arteries - drug effects Carotid Arteries - metabolism Carotid Arteries - pathology Carotid Artery Injuries - drug therapy Carotid Artery Injuries - metabolism Carotid Artery Injuries - pathology Dapagliflozin Disease Models, Animal Endothelial dysfunction Glucosides - pharmacology Human health and pathology Life Sciences Losartan - pharmacology Male Neointima Neointima formation Nitric Oxide Synthase Type III - metabolism Oxidative Stress - drug effects Pharmaceutical sciences Pharmacology Purinergic signaling Rats Rats, Wistar SGLT2 Sodium-Glucose Transporter 2 Inhibitors - pharmacology Transforming Growth Factor beta1 - metabolism Vascular Remodeling - drug effects |
| title | Potential of dapagliflozin to prevent vascular remodeling in the rat carotid artery following balloon injury |
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