Intraperitoneal infusion of homocysteine increases intimal hyperplasia in balloon-injured rat carotid arteries
Hyperhomocysteinemia is a significant risk factor in atherosclerosis and thrombosis. However, its role in the development of intimal hyperplasia after arterial reconstructive procedures remains uncertain. We therefore studied the effect of homocysteine on intimal hyperplasia in a rat model of caroti...
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| Veröffentlicht in: | Atherosclerosis 2002, Vol.160 (1), p.103-114 |
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| description | Hyperhomocysteinemia is a significant risk factor in atherosclerosis and thrombosis. However, its role in the development of intimal hyperplasia after arterial reconstructive procedures remains uncertain. We therefore studied the effect of homocysteine on intimal hyperplasia in a rat model of carotid artery balloon injury. Twenty-four Spraque–Dawley rats were divided into three groups: control (saline infusion), and low dose (0.14 mg/day) and high dose (0.71 mg/day) homocysteine delivered continuously via osmotic pumps implanted intraperitoneally. All animals underwent left common carotid artery balloon denudation with sacrifice after 14 days. Plasma homocysteine levels, intimal hyperplasia, and cell proliferation of rat carotid arteries were determined. In vitro rat smooth muscle cell (SMC) proliferation with homocysteine treatment was also performed. Plasma homocysteine levels at sacrifice were 1.80±0.35, 2.65±0.05 and 3.50±0.22 μM in three groups, respectively. Intimal hyperplasia developed in all balloon-injured arteries in both control and homocysteine-treated animals. The intimal area and intima/media area ratio were increased by 92% (
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| doi_str_mv | 10.1016/S0021-9150(01)00573-1 |
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P<0.05) and 105% (
P<0.05), respectively, in the high dose-homocysteine-treated animals as compared to the control animals. Homocysteine (high dose) also significantly promoted the intimal cell proliferation (bromodeoxyuridine incorporation) by 2.2-fold as compared to controls. Furthermore, homocysteine treatment in the cell culture study showed a concentration-dependent increase of rat SMC proliferation. These data demonstrate that the continuous intraperitoneal administration of homocysteine significantly increases intimal hyperplasia and SMC proliferation after carotid artery balloon injury in the rat as well as in vitro SMC proliferation. This study suggests that, following arterial reconstructive procedures, elevated plasma homocysteine may increase the complications of clinical restenoses that are associated with intimal hyperplasia.</description><identifier>ISSN: 0021-9150</identifier><identifier>EISSN: 1879-1484</identifier><identifier>DOI: 10.1016/S0021-9150(01)00573-1</identifier><identifier>PMID: 11755927</identifier><language>eng</language><publisher>Amsterdam: Elsevier Ireland Ltd</publisher><subject>Animals ; Atherosclerosis (general aspects, experimental research) ; Biological and medical sciences ; Blood and lymphatic vessels ; Cardiology. Vascular system ; Carotid Artery Injuries ; Catheterization - adverse effects ; Cell proliferation ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Homocysteine ; Homocysteine - administration & dosage ; Homocysteine - blood ; Hyperplasia - drug therapy ; Hyperplasia - etiology ; Infusions, Parenteral ; Intimal hyperplasia ; Male ; Medical sciences ; Muscle, Smooth, Vascular - drug effects ; Rat ; Rats ; Rats, Sprague-Dawley ; Tunica Intima - pathology</subject><ispartof>Atherosclerosis, 2002, Vol.160 (1), p.103-114</ispartof><rights>2002 Elsevier Science Ireland Ltd</rights><rights>2002 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c443t-a5c3e100e8b329ae5aba502f52d268d7f29f3671d868b6deb31ebef88f9153733</citedby><cites>FETCH-LOGICAL-c443t-a5c3e100e8b329ae5aba502f52d268d7f29f3671d868b6deb31ebef88f9153733</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/S0021-9150(01)00573-1$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,777,781,3537,4010,27904,27905,27906,45976</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=13430899$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11755927$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Changyi</creatorcontrib><creatorcontrib>Surowiec, Scott M</creatorcontrib><creatorcontrib>Morsy, Amro H</creatorcontrib><creatorcontrib>Ma, Minhui</creatorcontrib><title>Intraperitoneal infusion of homocysteine increases intimal hyperplasia in balloon-injured rat carotid arteries</title><title>Atherosclerosis</title><addtitle>Atherosclerosis</addtitle><description>Hyperhomocysteinemia is a significant risk factor in atherosclerosis and thrombosis. However, its role in the development of intimal hyperplasia after arterial reconstructive procedures remains uncertain. We therefore studied the effect of homocysteine on intimal hyperplasia in a rat model of carotid artery balloon injury. Twenty-four Spraque–Dawley rats were divided into three groups: control (saline infusion), and low dose (0.14 mg/day) and high dose (0.71 mg/day) homocysteine delivered continuously via osmotic pumps implanted intraperitoneally. All animals underwent left common carotid artery balloon denudation with sacrifice after 14 days. Plasma homocysteine levels, intimal hyperplasia, and cell proliferation of rat carotid arteries were determined. In vitro rat smooth muscle cell (SMC) proliferation with homocysteine treatment was also performed. Plasma homocysteine levels at sacrifice were 1.80±0.35, 2.65±0.05 and 3.50±0.22 μM in three groups, respectively. Intimal hyperplasia developed in all balloon-injured arteries in both control and homocysteine-treated animals. The intimal area and intima/media area ratio were increased by 92% (
P<0.05) and 105% (
P<0.05), respectively, in the high dose-homocysteine-treated animals as compared to the control animals. Homocysteine (high dose) also significantly promoted the intimal cell proliferation (bromodeoxyuridine incorporation) by 2.2-fold as compared to controls. Furthermore, homocysteine treatment in the cell culture study showed a concentration-dependent increase of rat SMC proliferation. These data demonstrate that the continuous intraperitoneal administration of homocysteine significantly increases intimal hyperplasia and SMC proliferation after carotid artery balloon injury in the rat as well as in vitro SMC proliferation. This study suggests that, following arterial reconstructive procedures, elevated plasma homocysteine may increase the complications of clinical restenoses that are associated with intimal hyperplasia.</description><subject>Animals</subject><subject>Atherosclerosis (general aspects, experimental research)</subject><subject>Biological and medical sciences</subject><subject>Blood and lymphatic vessels</subject><subject>Cardiology. Vascular system</subject><subject>Carotid Artery Injuries</subject><subject>Catheterization - adverse effects</subject><subject>Cell proliferation</subject><subject>Disease Models, Animal</subject><subject>Dose-Response Relationship, Drug</subject><subject>Homocysteine</subject><subject>Homocysteine - administration & dosage</subject><subject>Homocysteine - blood</subject><subject>Hyperplasia - drug therapy</subject><subject>Hyperplasia - etiology</subject><subject>Infusions, Parenteral</subject><subject>Intimal hyperplasia</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Muscle, Smooth, Vascular - drug effects</subject><subject>Rat</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Tunica Intima - pathology</subject><issn>0021-9150</issn><issn>1879-1484</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkMFu1DAQhi1ERZfCI4ByAcEhxRPHiXNCqAJaqRKHwtma2GPVVdZebAdp3x5vd0WPnGx5vt8z8zH2BvglcBg-3XHeQTuB5B84fORcjqKFZ2wDapxa6FX_nG3-IefsZc4PnPN-BPWCnQOMUk7duGHhJpSEO0q-xEC4ND64NfsYmuia-7iNZp8L-UC1YBJhplxvxW8rer-vud2C2WN9a2ZclhhD68PDmsg2CUtjMMXibYOp1BaUX7Ezh0um16fzgv369vXn1XV7--P7zdWX29b0vSgtSiMIOCc1i25Ckjij5J2Tne0GZUfXTU4MI1g1qHmwNAugmZxSrm4rRiEu2Pvjv7sUf6-Ui976bGhZMFBcsx5BiJ6LqYLyCJoUc07k9C7V5dJeA9cH0fpRtD5Y1Bz0o2gNNff21GCdt2SfUiezFXh3AjAbXFzCYHx-4kQvuJoOA3w-clR1_PGUdDaegiHrE5mibfT_GeUvgjKczw</recordid><startdate>2002</startdate><enddate>2002</enddate><creator>Chen, Changyi</creator><creator>Surowiec, Scott M</creator><creator>Morsy, Amro H</creator><creator>Ma, Minhui</creator><general>Elsevier Ireland Ltd</general><general>Elsevier</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>7X8</scope></search><sort><creationdate>2002</creationdate><title>Intraperitoneal infusion of homocysteine increases intimal hyperplasia in balloon-injured rat carotid arteries</title><author>Chen, Changyi ; Surowiec, Scott M ; Morsy, Amro H ; Ma, Minhui</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c443t-a5c3e100e8b329ae5aba502f52d268d7f29f3671d868b6deb31ebef88f9153733</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Animals</topic><topic>Atherosclerosis (general aspects, experimental research)</topic><topic>Biological and medical sciences</topic><topic>Blood and lymphatic vessels</topic><topic>Cardiology. Vascular system</topic><topic>Carotid Artery Injuries</topic><topic>Catheterization - adverse effects</topic><topic>Cell proliferation</topic><topic>Disease Models, Animal</topic><topic>Dose-Response Relationship, Drug</topic><topic>Homocysteine</topic><topic>Homocysteine - administration & dosage</topic><topic>Homocysteine - blood</topic><topic>Hyperplasia - drug therapy</topic><topic>Hyperplasia - etiology</topic><topic>Infusions, Parenteral</topic><topic>Intimal hyperplasia</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Muscle, Smooth, Vascular - drug effects</topic><topic>Rat</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Tunica Intima - pathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Changyi</creatorcontrib><creatorcontrib>Surowiec, Scott M</creatorcontrib><creatorcontrib>Morsy, Amro H</creatorcontrib><creatorcontrib>Ma, Minhui</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>MEDLINE - Academic</collection><jtitle>Atherosclerosis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Changyi</au><au>Surowiec, Scott M</au><au>Morsy, Amro H</au><au>Ma, Minhui</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Intraperitoneal infusion of homocysteine increases intimal hyperplasia in balloon-injured rat carotid arteries</atitle><jtitle>Atherosclerosis</jtitle><addtitle>Atherosclerosis</addtitle><date>2002</date><risdate>2002</risdate><volume>160</volume><issue>1</issue><spage>103</spage><epage>114</epage><pages>103-114</pages><issn>0021-9150</issn><eissn>1879-1484</eissn><abstract>Hyperhomocysteinemia is a significant risk factor in atherosclerosis and thrombosis. However, its role in the development of intimal hyperplasia after arterial reconstructive procedures remains uncertain. We therefore studied the effect of homocysteine on intimal hyperplasia in a rat model of carotid artery balloon injury. Twenty-four Spraque–Dawley rats were divided into three groups: control (saline infusion), and low dose (0.14 mg/day) and high dose (0.71 mg/day) homocysteine delivered continuously via osmotic pumps implanted intraperitoneally. All animals underwent left common carotid artery balloon denudation with sacrifice after 14 days. Plasma homocysteine levels, intimal hyperplasia, and cell proliferation of rat carotid arteries were determined. In vitro rat smooth muscle cell (SMC) proliferation with homocysteine treatment was also performed. Plasma homocysteine levels at sacrifice were 1.80±0.35, 2.65±0.05 and 3.50±0.22 μM in three groups, respectively. Intimal hyperplasia developed in all balloon-injured arteries in both control and homocysteine-treated animals. The intimal area and intima/media area ratio were increased by 92% (
P<0.05) and 105% (
P<0.05), respectively, in the high dose-homocysteine-treated animals as compared to the control animals. Homocysteine (high dose) also significantly promoted the intimal cell proliferation (bromodeoxyuridine incorporation) by 2.2-fold as compared to controls. Furthermore, homocysteine treatment in the cell culture study showed a concentration-dependent increase of rat SMC proliferation. These data demonstrate that the continuous intraperitoneal administration of homocysteine significantly increases intimal hyperplasia and SMC proliferation after carotid artery balloon injury in the rat as well as in vitro SMC proliferation. This study suggests that, following arterial reconstructive procedures, elevated plasma homocysteine may increase the complications of clinical restenoses that are associated with intimal hyperplasia.</abstract><cop>Amsterdam</cop><pub>Elsevier Ireland Ltd</pub><pmid>11755927</pmid><doi>10.1016/S0021-9150(01)00573-1</doi><tpages>12</tpages></addata></record> |
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| subjects | Animals Atherosclerosis (general aspects, experimental research) Biological and medical sciences Blood and lymphatic vessels Cardiology. Vascular system Carotid Artery Injuries Catheterization - adverse effects Cell proliferation Disease Models, Animal Dose-Response Relationship, Drug Homocysteine Homocysteine - administration & dosage Homocysteine - blood Hyperplasia - drug therapy Hyperplasia - etiology Infusions, Parenteral Intimal hyperplasia Male Medical sciences Muscle, Smooth, Vascular - drug effects Rat Rats Rats, Sprague-Dawley Tunica Intima - pathology |
| title | Intraperitoneal infusion of homocysteine increases intimal hyperplasia in balloon-injured rat carotid arteries |
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