Effects of vitamin therapy on plasma total homocysteine, endothelial injury markers, and fibrinolysis in stroke patients
Hyperhomocystinemia linked to B-vitamin deficiency is prevalent and associated with increased risk for stroke. While in vitro studies suggest homocysteine directly injures vascular endothelial thrombomodulin (TM), inhibits vonWillebrand factor (vWF) synthesis, and blocks tissue plasminogen activator...
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| Veröffentlicht in: | Journal of stroke and cerebrovascular diseases 2002-01, Vol.11 (1), p.1-8 |
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| creator | Macko, Richard F. Kittner, Steven J. Ivey, Frederick M. Epstein, Anne Sparks, Mary J. Hebel, J.Richard Johnson, Constance C. Wityk, Robert J. Ueland, Per M. Refsum, Helga |
| description | Hyperhomocystinemia linked to B-vitamin deficiency is prevalent and associated with increased risk for stroke. While in vitro studies suggest homocysteine directly injures vascular endothelial thrombomodulin (TM), inhibits vonWillebrand factor (vWF) synthesis, and blocks tissue plasminogen activator (t-PA) receptor binding, these mechanisms and their reversibility by vitamin therapy are not established in humans. We investigated the effects of high-dose B-vitamin therapy on endogenous fibrinolysis and endothelial injury markers by randomizing 50 nonvitamin users with prior ischemic stroke to 3 months of treatment with multivitamins either containing folate (5 mg), B6 (100 mg), and B12 (1 mg), or lacking these components. Fasting before noon and post-methionine load plasma total homocysteine (tHcy), t-PA antigen levels, t-PA and plasminogen activator inhibitor (PAI) activities, total vWF antigen, and TM levels were measured before and after vitamin therapy. The primary analysis between treatment groups across time revealed no significant changes (P > .1) for any hematologic variables. However, within-groups analysis showed reductions of 23% in plasma TM (P < .005) and 27% in fasting tHcy levels (P < .0001) and a paradoxical 30% rise in vWF antigen levels (P < .05) after high-dose B-vitamin, treatment with no changes in controls. Pooled data revealed a significant and reproducible 20% to 28% decline in plasma t-PA activity after methionine load (n = 49, P < .02). Our findings demonstrate methionine load lowers plasma t-PA activity by a plasminogen activator inhibitor (PAI-1) independent mechanism that is not attenuated by 3 months of high-dose B-vitamin treatment. While not improving endogenous fibrinolysis profiles, these results provide initial evidence that B-vitamin treatment may selectively alter markers of vascular endothelial injury after stroke. Copyright © 2002 by National Stroke Association |
| doi_str_mv | 10.1053/jscd.2002.123968 |
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While in vitro studies suggest homocysteine directly injures vascular endothelial thrombomodulin (TM), inhibits vonWillebrand factor (vWF) synthesis, and blocks tissue plasminogen activator (t-PA) receptor binding, these mechanisms and their reversibility by vitamin therapy are not established in humans. We investigated the effects of high-dose B-vitamin therapy on endogenous fibrinolysis and endothelial injury markers by randomizing 50 nonvitamin users with prior ischemic stroke to 3 months of treatment with multivitamins either containing folate (5 mg), B6 (100 mg), and B12 (1 mg), or lacking these components. Fasting before noon and post-methionine load plasma total homocysteine (tHcy), t-PA antigen levels, t-PA and plasminogen activator inhibitor (PAI) activities, total vWF antigen, and TM levels were measured before and after vitamin therapy. The primary analysis between treatment groups across time revealed no significant changes (P > .1) for any hematologic variables. However, within-groups analysis showed reductions of 23% in plasma TM (P < .005) and 27% in fasting tHcy levels (P < .0001) and a paradoxical 30% rise in vWF antigen levels (P < .05) after high-dose B-vitamin, treatment with no changes in controls. Pooled data revealed a significant and reproducible 20% to 28% decline in plasma t-PA activity after methionine load (n = 49, P < .02). Our findings demonstrate methionine load lowers plasma t-PA activity by a plasminogen activator inhibitor (PAI-1) independent mechanism that is not attenuated by 3 months of high-dose B-vitamin treatment. While not improving endogenous fibrinolysis profiles, these results provide initial evidence that B-vitamin treatment may selectively alter markers of vascular endothelial injury after stroke. 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While in vitro studies suggest homocysteine directly injures vascular endothelial thrombomodulin (TM), inhibits vonWillebrand factor (vWF) synthesis, and blocks tissue plasminogen activator (t-PA) receptor binding, these mechanisms and their reversibility by vitamin therapy are not established in humans. We investigated the effects of high-dose B-vitamin therapy on endogenous fibrinolysis and endothelial injury markers by randomizing 50 nonvitamin users with prior ischemic stroke to 3 months of treatment with multivitamins either containing folate (5 mg), B6 (100 mg), and B12 (1 mg), or lacking these components. Fasting before noon and post-methionine load plasma total homocysteine (tHcy), t-PA antigen levels, t-PA and plasminogen activator inhibitor (PAI) activities, total vWF antigen, and TM levels were measured before and after vitamin therapy. The primary analysis between treatment groups across time revealed no significant changes (P > .1) for any hematologic variables. However, within-groups analysis showed reductions of 23% in plasma TM (P < .005) and 27% in fasting tHcy levels (P < .0001) and a paradoxical 30% rise in vWF antigen levels (P < .05) after high-dose B-vitamin, treatment with no changes in controls. Pooled data revealed a significant and reproducible 20% to 28% decline in plasma t-PA activity after methionine load (n = 49, P < .02). Our findings demonstrate methionine load lowers plasma t-PA activity by a plasminogen activator inhibitor (PAI-1) independent mechanism that is not attenuated by 3 months of high-dose B-vitamin treatment. While not improving endogenous fibrinolysis profiles, these results provide initial evidence that B-vitamin treatment may selectively alter markers of vascular endothelial injury after stroke. Copyright © 2002 by National Stroke Association</description><subject>Fibrinolysis</subject><subject>Homocysteine</subject><subject>Methionine load</subject><subject>Stroke</subject><subject>Thrombomodulin</subject><subject>Vitamin therapy</subject><issn>1052-3057</issn><issn>1532-8511</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><recordid>eNp1kE1v1DAQhi0Eoh9w54R84tQs_ojjhBuqCkWqxAXOlmNPVG8TO3i8VfPv8WpX4sRpRppnXul9CPnA2Y4zJT_v0fmdYEzsuJBD178il1xJ0fSK89d1Z0o0kil9Qa4Q94xxrnr1llxwPTDZt_0lebmbJnAFaZrocyh2CZGWR8h23WiKdJ0tLpaWVOxMH9OS3IYFQoQbCtGnSs6hXkLcH_JGF5ufIOMNtdHTKYw5xDRvGLACFEtOT0BXWwLEgu_Im8nOCO_P85r8_nb36_a-efj5_cft14fGiYGVxjqhtei4GJnvWw-goe2ctBo82MEzpTR00ImRj4PrWiGUEG6UXQXaiUknr8mnU-6a058DYDFLQAfzbCOkAxotBjnoTlWQnUCXE2KGyaw51Eab4cwcbZujbXO0bU6268vHc_ZhXMD_ezjrrcCXEwC14XOAbNDV9g58yNW68Sn8P_0v11-R_w</recordid><startdate>200201</startdate><enddate>200201</enddate><creator>Macko, Richard F.</creator><creator>Kittner, Steven J.</creator><creator>Ivey, Frederick M.</creator><creator>Epstein, Anne</creator><creator>Sparks, Mary J.</creator><creator>Hebel, J.Richard</creator><creator>Johnson, Constance C.</creator><creator>Wityk, Robert J.</creator><creator>Ueland, Per M.</creator><creator>Refsum, Helga</creator><general>Elsevier Inc</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>200201</creationdate><title>Effects of vitamin therapy on plasma total homocysteine, endothelial injury markers, and fibrinolysis in stroke patients</title><author>Macko, Richard F. ; Kittner, Steven J. ; Ivey, Frederick M. ; Epstein, Anne ; Sparks, Mary J. ; Hebel, J.Richard ; Johnson, Constance C. ; Wityk, Robert J. ; Ueland, Per M. ; Refsum, Helga</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c290t-ac2772612b0d84dee7e46c3a7edea9d0557e6e62b1b9c6422522cb36a7e4f03c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Fibrinolysis</topic><topic>Homocysteine</topic><topic>Methionine load</topic><topic>Stroke</topic><topic>Thrombomodulin</topic><topic>Vitamin therapy</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Macko, Richard F.</creatorcontrib><creatorcontrib>Kittner, Steven J.</creatorcontrib><creatorcontrib>Ivey, Frederick M.</creatorcontrib><creatorcontrib>Epstein, Anne</creatorcontrib><creatorcontrib>Sparks, Mary J.</creatorcontrib><creatorcontrib>Hebel, J.Richard</creatorcontrib><creatorcontrib>Johnson, Constance C.</creatorcontrib><creatorcontrib>Wityk, Robert J.</creatorcontrib><creatorcontrib>Ueland, Per M.</creatorcontrib><creatorcontrib>Refsum, Helga</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of stroke and cerebrovascular diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Macko, Richard F.</au><au>Kittner, Steven J.</au><au>Ivey, Frederick M.</au><au>Epstein, Anne</au><au>Sparks, Mary J.</au><au>Hebel, J.Richard</au><au>Johnson, Constance C.</au><au>Wityk, Robert J.</au><au>Ueland, Per M.</au><au>Refsum, Helga</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of vitamin therapy on plasma total homocysteine, endothelial injury markers, and fibrinolysis in stroke patients</atitle><jtitle>Journal of stroke and cerebrovascular diseases</jtitle><addtitle>J Stroke Cerebrovasc Dis</addtitle><date>2002-01</date><risdate>2002</risdate><volume>11</volume><issue>1</issue><spage>1</spage><epage>8</epage><pages>1-8</pages><issn>1052-3057</issn><eissn>1532-8511</eissn><abstract>Hyperhomocystinemia linked to B-vitamin deficiency is prevalent and associated with increased risk for stroke. While in vitro studies suggest homocysteine directly injures vascular endothelial thrombomodulin (TM), inhibits vonWillebrand factor (vWF) synthesis, and blocks tissue plasminogen activator (t-PA) receptor binding, these mechanisms and their reversibility by vitamin therapy are not established in humans. We investigated the effects of high-dose B-vitamin therapy on endogenous fibrinolysis and endothelial injury markers by randomizing 50 nonvitamin users with prior ischemic stroke to 3 months of treatment with multivitamins either containing folate (5 mg), B6 (100 mg), and B12 (1 mg), or lacking these components. Fasting before noon and post-methionine load plasma total homocysteine (tHcy), t-PA antigen levels, t-PA and plasminogen activator inhibitor (PAI) activities, total vWF antigen, and TM levels were measured before and after vitamin therapy. The primary analysis between treatment groups across time revealed no significant changes (P > .1) for any hematologic variables. However, within-groups analysis showed reductions of 23% in plasma TM (P < .005) and 27% in fasting tHcy levels (P < .0001) and a paradoxical 30% rise in vWF antigen levels (P < .05) after high-dose B-vitamin, treatment with no changes in controls. Pooled data revealed a significant and reproducible 20% to 28% decline in plasma t-PA activity after methionine load (n = 49, P < .02). Our findings demonstrate methionine load lowers plasma t-PA activity by a plasminogen activator inhibitor (PAI-1) independent mechanism that is not attenuated by 3 months of high-dose B-vitamin treatment. While not improving endogenous fibrinolysis profiles, these results provide initial evidence that B-vitamin treatment may selectively alter markers of vascular endothelial injury after stroke. Copyright © 2002 by National Stroke Association</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>17903848</pmid><doi>10.1053/jscd.2002.123968</doi><tpages>8</tpages></addata></record> |
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| subjects | Fibrinolysis Homocysteine Methionine load Stroke Thrombomodulin Vitamin therapy |
| title | Effects of vitamin therapy on plasma total homocysteine, endothelial injury markers, and fibrinolysis in stroke patients |
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