Platelet Integrin αIIbβ3 Inhibitor Rescues Progression of Apoptosis in Human Platelets

BACKGROUND Apoptosis plays an important role in the physiology of platelet function. We aimed to detect the effect of the platelet integrin αIIbβ3 inhibitor, tirofiban, on apoptotic events, including mitochondrial inner-membrane potential (ΔΨm), phosphatidylserine (PS) exposure on platelet surface,...

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Veröffentlicht in:Medical science monitor 2016-11, Vol.22, p.4261-4270
Hauptverfasser: Zhu, Jie, Wang, Qinghang, Nie, Yumei, Yan, Rong, Dai, Kesheng, Zhou, Birong
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container_start_page 4261
container_title Medical science monitor
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creator Zhu, Jie
Wang, Qinghang
Nie, Yumei
Yan, Rong
Dai, Kesheng
Zhou, Birong
description BACKGROUND Apoptosis plays an important role in the physiology of platelet function. We aimed to detect the effect of the platelet integrin αIIbβ3 inhibitor, tirofiban, on apoptotic events, including mitochondrial inner-membrane potential (ΔΨm), phosphatidylserine (PS) exposure on platelet surface, and the generation of reactive oxygen species (ROS), when washed platelets were stimulated with thrombin. MATERIAL AND METHODS The study included washed platelets from healthy humans, divided into 4 groups: vehicle, and tirofiban (0.05 μg/ml, 0.25 μg/ml, and 0.5 μg/ml). Platelets were pretreated with vehicle or tirofiban and incubated at 37°C with agitation for 6 h and 24 h. Before thrombin addition, the vehicle group divided into 2 equal groups. Except one vehicle group, the other 4 groups were all stimulated with thrombin (1 U/ml) for 30 min at 37°C. Using flow cytometry, we studied the DYm and PS exposure on platelet surfaces, and the generation of ROS in platelets. RESULTS We observed that at the time of 6 h and 24 h, thrombin-stimulated vehicle platelets induced significant depo-larization of ΔΨm, higher PS exposure, and increased ROS production compared with the vehicle group (P
doi_str_mv 10.12659/MSM.900820
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We aimed to detect the effect of the platelet integrin αIIbβ3 inhibitor, tirofiban, on apoptotic events, including mitochondrial inner-membrane potential (ΔΨm), phosphatidylserine (PS) exposure on platelet surface, and the generation of reactive oxygen species (ROS), when washed platelets were stimulated with thrombin. MATERIAL AND METHODS The study included washed platelets from healthy humans, divided into 4 groups: vehicle, and tirofiban (0.05 μg/ml, 0.25 μg/ml, and 0.5 μg/ml). Platelets were pretreated with vehicle or tirofiban and incubated at 37°C with agitation for 6 h and 24 h. Before thrombin addition, the vehicle group divided into 2 equal groups. Except one vehicle group, the other 4 groups were all stimulated with thrombin (1 U/ml) for 30 min at 37°C. Using flow cytometry, we studied the DYm and PS exposure on platelet surfaces, and the generation of ROS in platelets. RESULTS We observed that at the time of 6 h and 24 h, thrombin-stimulated vehicle platelets induced significant depo-larization of ΔΨm, higher PS exposure, and increased ROS production compared with the vehicle group (P&lt;0.01). However, the tirofiban group had significantly more recovery of DYm, PS exposure, and ROS production compared with the thrombin group (P&lt;0.01). CONCLUSIONS The platelet integrin αIIbβ3 inhibitor, tirofiban, inhibits the depolarization of DYm, PS exposure on platelet surface, and ROS production when stimulated with thrombin. These results suggest that αIIbβ3 inhibitor inhibits the initiation of apoptosis in platelets, showing a potential clinical application of tirofiban as an apoptosis inhibitor.</description><identifier>ISSN: 1643-3750</identifier><identifier>ISSN: 1234-1010</identifier><identifier>EISSN: 1643-3750</identifier><identifier>DOI: 10.12659/MSM.900820</identifier><identifier>PMID: 27827357</identifier><language>eng</language><publisher>United States: International Scientific Literature, Inc</publisher><subject>Adult ; Apoptosis - drug effects ; Blood Platelets - cytology ; Blood Platelets - drug effects ; Blood Platelets - metabolism ; Female ; Humans ; Lab/In Vitro Research ; Male ; Membrane Potential, Mitochondrial ; Platelet Aggregation Inhibitors - pharmacology ; Platelet Glycoprotein GPIIb-IIIa Complex - antagonists &amp; inhibitors ; Platelet Glycoprotein GPIIb-IIIa Complex - metabolism ; Reactive Oxygen Species - metabolism ; Thrombin - metabolism ; Tirofiban ; Tyrosine - analogs &amp; derivatives ; Tyrosine - pharmacology</subject><ispartof>Medical science monitor, 2016-11, Vol.22, p.4261-4270</ispartof><rights>Med Sci Monit, 2016 2016</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c2960-97c815d011bde9e6b09dc465300fa66ff1c5cf9977d1503e2bef9589d0d7bf393</citedby><cites>FETCH-LOGICAL-c2960-97c815d011bde9e6b09dc465300fa66ff1c5cf9977d1503e2bef9589d0d7bf393</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5108368/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5108368/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27903,27904,53769,53771</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27827357$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhu, Jie</creatorcontrib><creatorcontrib>Wang, Qinghang</creatorcontrib><creatorcontrib>Nie, Yumei</creatorcontrib><creatorcontrib>Yan, Rong</creatorcontrib><creatorcontrib>Dai, Kesheng</creatorcontrib><creatorcontrib>Zhou, Birong</creatorcontrib><title>Platelet Integrin αIIbβ3 Inhibitor Rescues Progression of Apoptosis in Human Platelets</title><title>Medical science monitor</title><addtitle>Med Sci Monit</addtitle><description>BACKGROUND Apoptosis plays an important role in the physiology of platelet function. We aimed to detect the effect of the platelet integrin αIIbβ3 inhibitor, tirofiban, on apoptotic events, including mitochondrial inner-membrane potential (ΔΨm), phosphatidylserine (PS) exposure on platelet surface, and the generation of reactive oxygen species (ROS), when washed platelets were stimulated with thrombin. MATERIAL AND METHODS The study included washed platelets from healthy humans, divided into 4 groups: vehicle, and tirofiban (0.05 μg/ml, 0.25 μg/ml, and 0.5 μg/ml). Platelets were pretreated with vehicle or tirofiban and incubated at 37°C with agitation for 6 h and 24 h. Before thrombin addition, the vehicle group divided into 2 equal groups. Except one vehicle group, the other 4 groups were all stimulated with thrombin (1 U/ml) for 30 min at 37°C. Using flow cytometry, we studied the DYm and PS exposure on platelet surfaces, and the generation of ROS in platelets. RESULTS We observed that at the time of 6 h and 24 h, thrombin-stimulated vehicle platelets induced significant depo-larization of ΔΨm, higher PS exposure, and increased ROS production compared with the vehicle group (P&lt;0.01). However, the tirofiban group had significantly more recovery of DYm, PS exposure, and ROS production compared with the thrombin group (P&lt;0.01). CONCLUSIONS The platelet integrin αIIbβ3 inhibitor, tirofiban, inhibits the depolarization of DYm, PS exposure on platelet surface, and ROS production when stimulated with thrombin. These results suggest that αIIbβ3 inhibitor inhibits the initiation of apoptosis in platelets, showing a potential clinical application of tirofiban as an apoptosis inhibitor.</description><subject>Adult</subject><subject>Apoptosis - drug effects</subject><subject>Blood Platelets - cytology</subject><subject>Blood Platelets - drug effects</subject><subject>Blood Platelets - metabolism</subject><subject>Female</subject><subject>Humans</subject><subject>Lab/In Vitro Research</subject><subject>Male</subject><subject>Membrane Potential, Mitochondrial</subject><subject>Platelet Aggregation Inhibitors - pharmacology</subject><subject>Platelet Glycoprotein GPIIb-IIIa Complex - antagonists &amp; inhibitors</subject><subject>Platelet Glycoprotein GPIIb-IIIa Complex - metabolism</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>Thrombin - metabolism</subject><subject>Tirofiban</subject><subject>Tyrosine - analogs &amp; derivatives</subject><subject>Tyrosine - pharmacology</subject><issn>1643-3750</issn><issn>1234-1010</issn><issn>1643-3750</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkctKAzEUhoMotlZX7mWWgkw9SZrMZCOUorbQYvEC7sJMJmkj00lNpoKPpQ_SZ3KwF3SVQ85_vnP5ETrH0MWEM3E9eZp0BUBK4AC1Me_RmCYMDv_ELXQSwhsASTmwY9QiSUoSypI2ep2WWa1LXUejqtYzb6to_TUa5etv2vzMbW5r56NHHdRKh2jq3czrEKyrImei_tItaxdsiJqy4WqRVdEOF07RkcnKoM-2bwe93N0-D4bx-OF-NOiPY0UEh1gkKsWsAIzzQgvNcxCF6nFGAUzGuTFYMWWESJICM6Ca5NoIlooCiiQ3VNAOutlwl6t8oQulq9pnpVx6u8j8p3SZlf8zlZ3LmfuQDENKedoALrcA796bJWu5sEHpsswq7VZB4pQKTATp0UZ6tZEq70Lw2uzbYJC_XsjGC7nxolFf_J1sr90dn_4Aa5qHNQ</recordid><startdate>20161109</startdate><enddate>20161109</enddate><creator>Zhu, Jie</creator><creator>Wang, Qinghang</creator><creator>Nie, Yumei</creator><creator>Yan, Rong</creator><creator>Dai, Kesheng</creator><creator>Zhou, Birong</creator><general>International Scientific Literature, 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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20161109</creationdate><title>Platelet Integrin αIIbβ3 Inhibitor Rescues Progression of Apoptosis in Human Platelets</title><author>Zhu, Jie ; Wang, Qinghang ; Nie, Yumei ; Yan, Rong ; Dai, Kesheng ; Zhou, Birong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c2960-97c815d011bde9e6b09dc465300fa66ff1c5cf9977d1503e2bef9589d0d7bf393</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Adult</topic><topic>Apoptosis - drug effects</topic><topic>Blood Platelets - cytology</topic><topic>Blood Platelets - drug effects</topic><topic>Blood Platelets - metabolism</topic><topic>Female</topic><topic>Humans</topic><topic>Lab/In Vitro Research</topic><topic>Male</topic><topic>Membrane Potential, Mitochondrial</topic><topic>Platelet Aggregation Inhibitors - pharmacology</topic><topic>Platelet Glycoprotein GPIIb-IIIa Complex - antagonists &amp; inhibitors</topic><topic>Platelet Glycoprotein GPIIb-IIIa Complex - metabolism</topic><topic>Reactive Oxygen Species - metabolism</topic><topic>Thrombin - metabolism</topic><topic>Tirofiban</topic><topic>Tyrosine - analogs &amp; derivatives</topic><topic>Tyrosine - pharmacology</topic><toplevel>online_resources</toplevel><creatorcontrib>Zhu, Jie</creatorcontrib><creatorcontrib>Wang, Qinghang</creatorcontrib><creatorcontrib>Nie, Yumei</creatorcontrib><creatorcontrib>Yan, Rong</creatorcontrib><creatorcontrib>Dai, Kesheng</creatorcontrib><creatorcontrib>Zhou, Birong</creatorcontrib><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>PubMed Central (Full Participant titles)</collection><jtitle>Medical science monitor</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhu, Jie</au><au>Wang, Qinghang</au><au>Nie, Yumei</au><au>Yan, Rong</au><au>Dai, Kesheng</au><au>Zhou, Birong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Platelet Integrin αIIbβ3 Inhibitor Rescues Progression of Apoptosis in Human Platelets</atitle><jtitle>Medical science monitor</jtitle><addtitle>Med Sci Monit</addtitle><date>2016-11-09</date><risdate>2016</risdate><volume>22</volume><spage>4261</spage><epage>4270</epage><pages>4261-4270</pages><issn>1643-3750</issn><issn>1234-1010</issn><eissn>1643-3750</eissn><abstract>BACKGROUND Apoptosis plays an important role in the physiology of platelet function. 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RESULTS We observed that at the time of 6 h and 24 h, thrombin-stimulated vehicle platelets induced significant depo-larization of ΔΨm, higher PS exposure, and increased ROS production compared with the vehicle group (P&lt;0.01). However, the tirofiban group had significantly more recovery of DYm, PS exposure, and ROS production compared with the thrombin group (P&lt;0.01). CONCLUSIONS The platelet integrin αIIbβ3 inhibitor, tirofiban, inhibits the depolarization of DYm, PS exposure on platelet surface, and ROS production when stimulated with thrombin. These results suggest that αIIbβ3 inhibitor inhibits the initiation of apoptosis in platelets, showing a potential clinical application of tirofiban as an apoptosis inhibitor.</abstract><cop>United States</cop><pub>International Scientific Literature, Inc</pub><pmid>27827357</pmid><doi>10.12659/MSM.900820</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record>
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subjects Adult
Apoptosis - drug effects
Blood Platelets - cytology
Blood Platelets - drug effects
Blood Platelets - metabolism
Female
Humans
Lab/In Vitro Research
Male
Membrane Potential, Mitochondrial
Platelet Aggregation Inhibitors - pharmacology
Platelet Glycoprotein GPIIb-IIIa Complex - antagonists & inhibitors
Platelet Glycoprotein GPIIb-IIIa Complex - metabolism
Reactive Oxygen Species - metabolism
Thrombin - metabolism
Tirofiban
Tyrosine - analogs & derivatives
Tyrosine - pharmacology
title Platelet Integrin αIIbβ3 Inhibitor Rescues Progression of Apoptosis in Human Platelets
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