Apolipoprotein(a) Enhances Platelet Responses to the Thrombin Receptor-Activating Peptide SFLLRN
Elevated levels of lipoprotein(a) [Lp(a)] are correlated with an increased risk of atherosclerotic disease. We examined the effect of recombinant apolipoprotein(a) [r-apo(a)] and Lp(a) on responses of washed human platelets, prelabeled in the dense granules with [() C]serotonin and suspended in Tyro...
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| Veröffentlicht in: | Arteriosclerosis, thrombosis, and vascular biology thrombosis, and vascular biology, 1998-09, Vol.18 (9), p.1393-1399 |
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| creator | Rand, Margaret L Sangrar, Waheed Hancock, Mark A Taylor, Desiree M Marcovina, Santica M Packham, Marian A Koschinsky, Marlys L |
| description | Elevated levels of lipoprotein(a) [Lp(a)] are correlated with an increased risk of atherosclerotic disease. We examined the effect of recombinant apolipoprotein(a) [r-apo(a)] and Lp(a) on responses of washed human platelets, prelabeled in the dense granules with [() C]serotonin and suspended in Tyrode's solution, to ADP and the thrombin receptor-activating peptide SFLLRN. No effect of the 17 kringle (K), 12K, or 6K r-apo(a) derivatives (at concentrations of 0.35 and 0.7 [micro sign]mol/L) or Lp(a) (up to 0.1 [micro sign]mol/L) on primary ADP-induced platelet aggregation was observed. In contrast, weak platelet responses stimulated by 7.5 [micro sign]mol/L SFLLRN were significantly enhanced by the r-apo(a) derivatives; eg, 0.7 [micro sign]mol/L 17K r-apo(a) increased aggregation from 15 +/- 4% to 58 +/- 6%, release of [() C]serotonin from 9 +/- 3% to 36 +/- 6%, and formation of thromboxane A2, measured as its stable metabolite thromboxane B2, from 7 +/- 1 to 29 +/- 5 ng/10 platelets (n=3; P |
| doi_str_mv | 10.1161/01.atv.18.9.1393 |
| format | Article |
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We examined the effect of recombinant apolipoprotein(a) [r-apo(a)] and Lp(a) on responses of washed human platelets, prelabeled in the dense granules with [() C]serotonin and suspended in Tyrode's solution, to ADP and the thrombin receptor-activating peptide SFLLRN. No effect of the 17 kringle (K), 12K, or 6K r-apo(a) derivatives (at concentrations of 0.35 and 0.7 [micro sign]mol/L) or Lp(a) (up to 0.1 [micro sign]mol/L) on primary ADP-induced platelet aggregation was observed. In contrast, weak platelet responses stimulated by 7.5 [micro sign]mol/L SFLLRN were significantly enhanced by the r-apo(a) derivatives; eg, 0.7 [micro sign]mol/L 17K r-apo(a) increased aggregation from 15 +/- 4% to 58 +/- 6%, release of [() C]serotonin from 9 +/- 3% to 36 +/- 6%, and formation of thromboxane A2, measured as its stable metabolite thromboxane B2, from 7 +/- 1 to 29 +/- 5 ng/10 platelets (n=3; P<0.04 to 0.015). Significant enhancement of aggregation and release of granule contents was observed at a concentration of 17K r-apo(a) as low as 0.175 [micro sign]mol/L. Purified Lp(a) (0.25 to 0.1 [micro sign]mol/L) also enhanced SFLLRN-induced aggregation and release in a dose-dependent manner. Although plasminogen (0.7 and 1.5 [micro sign]mol/L) and low density lipoprotein (0.025 to 0.1 [micro sign]mol/L) both exhibited potentiating effects on SFLLRN-mediated platelet aggregation, the magnitude of the responses was less than that observed with either the r-apo(a) derivatives or Lp(a). The enhanced responses of platelets via the protease-activated receptor-1 thrombin receptor in the presence of Lp(a) may contribute to the increased risk of thromboembolic complications of atherosclerosis associated with this lipoprotein. (Arterioscler Thromb Vasc Biol. 1998;18:1393-1399.)</description><identifier>ISSN: 1079-5642</identifier><identifier>EISSN: 1524-4636</identifier><identifier>DOI: 10.1161/01.atv.18.9.1393</identifier><identifier>PMID: 9743227</identifier><identifier>CODEN: ATVBFA</identifier><language>eng</language><publisher>Philadelphia, PA: American Heart Association, Inc</publisher><subject>Adenosine Diphosphate - pharmacology ; Apolipoproteins A - pharmacology ; Atherosclerosis (general aspects, experimental research) ; Biological and medical sciences ; Blood and lymphatic vessels ; Blood Platelets - drug effects ; Cardiology. Vascular system ; Cell Line ; Embryo, Mammalian ; Humans ; Kidney ; Medical sciences ; Peptide Fragments - pharmacology ; Platelet Activation - drug effects ; Platelet Aggregation - drug effects ; Receptors, Thrombin - drug effects ; Receptors, Thrombin - physiology ; Recombinant Proteins - pharmacology</subject><ispartof>Arteriosclerosis, thrombosis, and vascular biology, 1998-09, Vol.18 (9), p.1393-1399</ispartof><rights>1998 American Heart Association, Inc.</rights><rights>1998 INIST-CNRS</rights><rights>Copyright American Heart Association, Inc. Sep 1998</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5376-52f51c4df18afb3652e18c7437e886b2e0441d509132ff581f758009389b7a33</citedby><cites>FETCH-LOGICAL-c5376-52f51c4df18afb3652e18c7437e886b2e0441d509132ff581f758009389b7a33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=2386526$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9743227$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Rand, Margaret L</creatorcontrib><creatorcontrib>Sangrar, Waheed</creatorcontrib><creatorcontrib>Hancock, Mark A</creatorcontrib><creatorcontrib>Taylor, Desiree M</creatorcontrib><creatorcontrib>Marcovina, Santica M</creatorcontrib><creatorcontrib>Packham, Marian A</creatorcontrib><creatorcontrib>Koschinsky, Marlys L</creatorcontrib><title>Apolipoprotein(a) Enhances Platelet Responses to the Thrombin Receptor-Activating Peptide SFLLRN</title><title>Arteriosclerosis, thrombosis, and vascular biology</title><addtitle>Arterioscler Thromb Vasc Biol</addtitle><description>Elevated levels of lipoprotein(a) [Lp(a)] are correlated with an increased risk of atherosclerotic disease. We examined the effect of recombinant apolipoprotein(a) [r-apo(a)] and Lp(a) on responses of washed human platelets, prelabeled in the dense granules with [() C]serotonin and suspended in Tyrode's solution, to ADP and the thrombin receptor-activating peptide SFLLRN. No effect of the 17 kringle (K), 12K, or 6K r-apo(a) derivatives (at concentrations of 0.35 and 0.7 [micro sign]mol/L) or Lp(a) (up to 0.1 [micro sign]mol/L) on primary ADP-induced platelet aggregation was observed. In contrast, weak platelet responses stimulated by 7.5 [micro sign]mol/L SFLLRN were significantly enhanced by the r-apo(a) derivatives; eg, 0.7 [micro sign]mol/L 17K r-apo(a) increased aggregation from 15 +/- 4% to 58 +/- 6%, release of [() C]serotonin from 9 +/- 3% to 36 +/- 6%, and formation of thromboxane A2, measured as its stable metabolite thromboxane B2, from 7 +/- 1 to 29 +/- 5 ng/10 platelets (n=3; P<0.04 to 0.015). Significant enhancement of aggregation and release of granule contents was observed at a concentration of 17K r-apo(a) as low as 0.175 [micro sign]mol/L. Purified Lp(a) (0.25 to 0.1 [micro sign]mol/L) also enhanced SFLLRN-induced aggregation and release in a dose-dependent manner. Although plasminogen (0.7 and 1.5 [micro sign]mol/L) and low density lipoprotein (0.025 to 0.1 [micro sign]mol/L) both exhibited potentiating effects on SFLLRN-mediated platelet aggregation, the magnitude of the responses was less than that observed with either the r-apo(a) derivatives or Lp(a). The enhanced responses of platelets via the protease-activated receptor-1 thrombin receptor in the presence of Lp(a) may contribute to the increased risk of thromboembolic complications of atherosclerosis associated with this lipoprotein. (Arterioscler Thromb Vasc Biol. 1998;18:1393-1399.)</description><subject>Adenosine Diphosphate - pharmacology</subject><subject>Apolipoproteins A - pharmacology</subject><subject>Atherosclerosis (general aspects, experimental research)</subject><subject>Biological and medical sciences</subject><subject>Blood and lymphatic vessels</subject><subject>Blood Platelets - drug effects</subject><subject>Cardiology. Vascular system</subject><subject>Cell Line</subject><subject>Embryo, Mammalian</subject><subject>Humans</subject><subject>Kidney</subject><subject>Medical sciences</subject><subject>Peptide Fragments - pharmacology</subject><subject>Platelet Activation - drug effects</subject><subject>Platelet Aggregation - drug effects</subject><subject>Receptors, Thrombin - drug effects</subject><subject>Receptors, Thrombin - physiology</subject><subject>Recombinant Proteins - pharmacology</subject><issn>1079-5642</issn><issn>1524-4636</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1998</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkU1v1DAQhiMEKqVw54IUIYTKIcHjr9jHVdUWpBVUZcXVONkJSfHGqe204t_j1a564GDZM-8zo5nXRfEWSA0g4TOB2qaHGlSta2CaPStOQVBeccnk8_wmja6E5PRl8SrGO0IIp5ScFCe64YzS5rT4tZq9G2c_B59wnM7tp_JyGuzUYSxvnE3oMJW3GGc_xZxKvkwDlpsh-F07TlnpcE4-VKsujQ82jdPv8iZnxi2WP67W69tvr4sXvXUR3xzvs2Jzdbm5-FKtv19_vVitq06wRlaC9gI6vu1B2b5lUlAE1eUpG1RKthQJ57AVRAOjfS8U9I1QhGimdNtYxs6Kj4e2eZH7BWMyuzF26Jyd0C_RNEwTBkJn8P1_4J1fwpRHMzS7o3mj9xA5QF3wMQbszRzGnQ1_DRCzN94QMKvNTwPKaLM3Ppe8O_Zd2h1unwqOTmf9w1G3sbOuD9njMT5hlKm8s8wYP2CP3iUM8Y9bHjGYAa1Lg9l_IJNEVKC1IjqHVT5Esn_8NZkv</recordid><startdate>199809</startdate><enddate>199809</enddate><creator>Rand, Margaret L</creator><creator>Sangrar, Waheed</creator><creator>Hancock, Mark A</creator><creator>Taylor, Desiree M</creator><creator>Marcovina, Santica M</creator><creator>Packham, Marian A</creator><creator>Koschinsky, Marlys L</creator><general>American Heart Association, Inc</general><general>Lippincott</general><scope>IQODW</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>K9.</scope><scope>7X8</scope></search><sort><creationdate>199809</creationdate><title>Apolipoprotein(a) Enhances Platelet Responses to the Thrombin Receptor-Activating Peptide SFLLRN</title><author>Rand, Margaret L ; Sangrar, Waheed ; Hancock, Mark A ; Taylor, Desiree M ; Marcovina, Santica M ; Packham, Marian A ; Koschinsky, Marlys L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5376-52f51c4df18afb3652e18c7437e886b2e0441d509132ff581f758009389b7a33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1998</creationdate><topic>Adenosine Diphosphate - pharmacology</topic><topic>Apolipoproteins A - pharmacology</topic><topic>Atherosclerosis (general aspects, experimental research)</topic><topic>Biological and medical sciences</topic><topic>Blood and lymphatic vessels</topic><topic>Blood Platelets - drug effects</topic><topic>Cardiology. Vascular system</topic><topic>Cell Line</topic><topic>Embryo, Mammalian</topic><topic>Humans</topic><topic>Kidney</topic><topic>Medical sciences</topic><topic>Peptide Fragments - pharmacology</topic><topic>Platelet Activation - drug effects</topic><topic>Platelet Aggregation - drug effects</topic><topic>Receptors, Thrombin - drug effects</topic><topic>Receptors, Thrombin - physiology</topic><topic>Recombinant Proteins - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rand, Margaret L</creatorcontrib><creatorcontrib>Sangrar, Waheed</creatorcontrib><creatorcontrib>Hancock, Mark A</creatorcontrib><creatorcontrib>Taylor, Desiree M</creatorcontrib><creatorcontrib>Marcovina, Santica M</creatorcontrib><creatorcontrib>Packham, Marian A</creatorcontrib><creatorcontrib>Koschinsky, Marlys L</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Arteriosclerosis, thrombosis, and vascular biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rand, Margaret L</au><au>Sangrar, Waheed</au><au>Hancock, Mark A</au><au>Taylor, Desiree M</au><au>Marcovina, Santica M</au><au>Packham, Marian A</au><au>Koschinsky, Marlys L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Apolipoprotein(a) Enhances Platelet Responses to the Thrombin Receptor-Activating Peptide SFLLRN</atitle><jtitle>Arteriosclerosis, thrombosis, and vascular biology</jtitle><addtitle>Arterioscler Thromb Vasc Biol</addtitle><date>1998-09</date><risdate>1998</risdate><volume>18</volume><issue>9</issue><spage>1393</spage><epage>1399</epage><pages>1393-1399</pages><issn>1079-5642</issn><eissn>1524-4636</eissn><coden>ATVBFA</coden><abstract>Elevated levels of lipoprotein(a) [Lp(a)] are correlated with an increased risk of atherosclerotic disease. We examined the effect of recombinant apolipoprotein(a) [r-apo(a)] and Lp(a) on responses of washed human platelets, prelabeled in the dense granules with [() C]serotonin and suspended in Tyrode's solution, to ADP and the thrombin receptor-activating peptide SFLLRN. No effect of the 17 kringle (K), 12K, or 6K r-apo(a) derivatives (at concentrations of 0.35 and 0.7 [micro sign]mol/L) or Lp(a) (up to 0.1 [micro sign]mol/L) on primary ADP-induced platelet aggregation was observed. In contrast, weak platelet responses stimulated by 7.5 [micro sign]mol/L SFLLRN were significantly enhanced by the r-apo(a) derivatives; eg, 0.7 [micro sign]mol/L 17K r-apo(a) increased aggregation from 15 +/- 4% to 58 +/- 6%, release of [() C]serotonin from 9 +/- 3% to 36 +/- 6%, and formation of thromboxane A2, measured as its stable metabolite thromboxane B2, from 7 +/- 1 to 29 +/- 5 ng/10 platelets (n=3; P<0.04 to 0.015). Significant enhancement of aggregation and release of granule contents was observed at a concentration of 17K r-apo(a) as low as 0.175 [micro sign]mol/L. Purified Lp(a) (0.25 to 0.1 [micro sign]mol/L) also enhanced SFLLRN-induced aggregation and release in a dose-dependent manner. Although plasminogen (0.7 and 1.5 [micro sign]mol/L) and low density lipoprotein (0.025 to 0.1 [micro sign]mol/L) both exhibited potentiating effects on SFLLRN-mediated platelet aggregation, the magnitude of the responses was less than that observed with either the r-apo(a) derivatives or Lp(a). The enhanced responses of platelets via the protease-activated receptor-1 thrombin receptor in the presence of Lp(a) may contribute to the increased risk of thromboembolic complications of atherosclerosis associated with this lipoprotein. (Arterioscler Thromb Vasc Biol. 1998;18:1393-1399.)</abstract><cop>Philadelphia, PA</cop><cop>Hagerstown, MD</cop><pub>American Heart Association, Inc</pub><pmid>9743227</pmid><doi>10.1161/01.atv.18.9.1393</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1079-5642 |
| ispartof | Arteriosclerosis, thrombosis, and vascular biology, 1998-09, Vol.18 (9), p.1393-1399 |
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| subjects | Adenosine Diphosphate - pharmacology Apolipoproteins A - pharmacology Atherosclerosis (general aspects, experimental research) Biological and medical sciences Blood and lymphatic vessels Blood Platelets - drug effects Cardiology. Vascular system Cell Line Embryo, Mammalian Humans Kidney Medical sciences Peptide Fragments - pharmacology Platelet Activation - drug effects Platelet Aggregation - drug effects Receptors, Thrombin - drug effects Receptors, Thrombin - physiology Recombinant Proteins - pharmacology |
| title | Apolipoprotein(a) Enhances Platelet Responses to the Thrombin Receptor-Activating Peptide SFLLRN |
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