Reconstituted High-Density Lipoprotein Stimulates Differentiation of Endothelial Progenitor Cells and Enhances Ischemia-Induced Angiogenesis
BACKGROUND—Plasma high-density lipoprotein (HDL) levels have an inverse correlation with incidence of ischemic heart disease as well as other atherosclerosis-related ischemic conditions. However, the molecular mechanism by which HDL prevents ischemic disease is not fully understood. Here, we investi...
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| Veröffentlicht in: | Arteriosclerosis, thrombosis, and vascular biology thrombosis, and vascular biology, 2007-04, Vol.27 (4), p.813-818 |
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| container_title | Arteriosclerosis, thrombosis, and vascular biology |
| container_volume | 27 |
| creator | Sumi, Makoto Sata, Masataka Miura, Shin-ichiro Rye, Kerry-Anne Toya, Naoki Kanaoka, Yuji Yanaga, Katsuhiko Ohki, Takao Saku, Keijiro Nagai, Ryozo |
| description | BACKGROUND—Plasma high-density lipoprotein (HDL) levels have an inverse correlation with incidence of ischemic heart disease as well as other atherosclerosis-related ischemic conditions. However, the molecular mechanism by which HDL prevents ischemic disease is not fully understood. Here, we investigated the effect of HDL on differentiation of endothelial progenitor cells and angiogenesis in murine ischemic hindlimb model.
METHODS AND RESULTS—Intravenous injection of reconstituted HDL (rHDL) significantly augmented blood flow recovery and increased capillary density in the ischemic leg. rHDL increased the number of bone marrow–derived cells incorporated into the newly formed capillaries in ischemic muscle. rHDL induced phosphorylation of Akt in human peripheral mononuclear cells. rHDL (50 to 100 μg apolipoprotein A-I/mL) promoted differentiation of peripheral mononuclear cells to endothelial progenitor cells in a dose-dependent manner. The effect of rHDL on endothelial progenitor cells differentiation was abrogated by coadministration of LY294002, an inhibitor of phosphatidylinositol 3-kinase. rHDL failed to promote angiogenesis in endothelial NO–deficient mice.
CONCLUSIONS—rHDL directly stimulates endothelial progenitor cell differentiation via phosphatidylinositol 3-kinase/Akt pathway and enhances ischemia-induced angiogenesis. rHDL may be useful in the treatment of patients with ischemic cardiovascular diseases. |
| doi_str_mv | 10.1161/01.ATV.0000259299.38843.64 |
| format | Article |
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METHODS AND RESULTS—Intravenous injection of reconstituted HDL (rHDL) significantly augmented blood flow recovery and increased capillary density in the ischemic leg. rHDL increased the number of bone marrow–derived cells incorporated into the newly formed capillaries in ischemic muscle. rHDL induced phosphorylation of Akt in human peripheral mononuclear cells. rHDL (50 to 100 μg apolipoprotein A-I/mL) promoted differentiation of peripheral mononuclear cells to endothelial progenitor cells in a dose-dependent manner. The effect of rHDL on endothelial progenitor cells differentiation was abrogated by coadministration of LY294002, an inhibitor of phosphatidylinositol 3-kinase. rHDL failed to promote angiogenesis in endothelial NO–deficient mice.
CONCLUSIONS—rHDL directly stimulates endothelial progenitor cell differentiation via phosphatidylinositol 3-kinase/Akt pathway and enhances ischemia-induced angiogenesis. rHDL may be useful in the treatment of patients with ischemic cardiovascular diseases.</description><identifier>ISSN: 1079-5642</identifier><identifier>EISSN: 1524-4636</identifier><identifier>DOI: 10.1161/01.ATV.0000259299.38843.64</identifier><identifier>PMID: 17272742</identifier><identifier>CODEN: ATVBFA</identifier><language>eng</language><publisher>Philadelphia, PA: American Heart Association, Inc</publisher><subject>Animals ; Atherosclerosis (general aspects, experimental research) ; Biological and medical sciences ; Blood and lymphatic vessels ; Blood vessels and receptors ; Bone Marrow - pathology ; Cardiology. Vascular system ; Cardiovascular system ; Cell Differentiation - drug effects ; Cells, Cultured ; Chimera ; Collateral Circulation - drug effects ; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous ; Endothelial Cells - pathology ; Fundamental and applied biological sciences. Psychology ; Hindlimb - blood supply ; Humans ; Ischemia - physiopathology ; Lipoproteins, HDL - pharmacology ; Male ; Medical sciences ; Mice ; Mice, Inbred Strains ; Mice, Knockout ; Neovascularization, Physiologic - drug effects ; Nitric Oxide Synthase Type III - deficiency ; Pharmacology. Drug treatments ; Phosphatidylinositol 3-Kinases - metabolism ; Proto-Oncogene Proteins c-akt - metabolism ; Regional Blood Flow - drug effects ; Signal Transduction ; Stem Cells - pathology ; Vasodilator agents. Cerebral vasodilators ; Vertebrates: cardiovascular system</subject><ispartof>Arteriosclerosis, thrombosis, and vascular biology, 2007-04, Vol.27 (4), p.813-818</ispartof><rights>2007 American Heart Association, Inc.</rights><rights>2007 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5534-c0c96bd7e6cf674056f2073f546a2ebf5c9af6b50399d2a328abbbf4017cd4b53</citedby><cites>FETCH-LOGICAL-c5534-c0c96bd7e6cf674056f2073f546a2ebf5c9af6b50399d2a328abbbf4017cd4b53</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=18635973$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17272742$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sumi, Makoto</creatorcontrib><creatorcontrib>Sata, Masataka</creatorcontrib><creatorcontrib>Miura, Shin-ichiro</creatorcontrib><creatorcontrib>Rye, Kerry-Anne</creatorcontrib><creatorcontrib>Toya, Naoki</creatorcontrib><creatorcontrib>Kanaoka, Yuji</creatorcontrib><creatorcontrib>Yanaga, Katsuhiko</creatorcontrib><creatorcontrib>Ohki, Takao</creatorcontrib><creatorcontrib>Saku, Keijiro</creatorcontrib><creatorcontrib>Nagai, Ryozo</creatorcontrib><title>Reconstituted High-Density Lipoprotein Stimulates Differentiation of Endothelial Progenitor Cells and Enhances Ischemia-Induced Angiogenesis</title><title>Arteriosclerosis, thrombosis, and vascular biology</title><addtitle>Arterioscler Thromb Vasc Biol</addtitle><description>BACKGROUND—Plasma high-density lipoprotein (HDL) levels have an inverse correlation with incidence of ischemic heart disease as well as other atherosclerosis-related ischemic conditions. However, the molecular mechanism by which HDL prevents ischemic disease is not fully understood. Here, we investigated the effect of HDL on differentiation of endothelial progenitor cells and angiogenesis in murine ischemic hindlimb model.
METHODS AND RESULTS—Intravenous injection of reconstituted HDL (rHDL) significantly augmented blood flow recovery and increased capillary density in the ischemic leg. rHDL increased the number of bone marrow–derived cells incorporated into the newly formed capillaries in ischemic muscle. rHDL induced phosphorylation of Akt in human peripheral mononuclear cells. rHDL (50 to 100 μg apolipoprotein A-I/mL) promoted differentiation of peripheral mononuclear cells to endothelial progenitor cells in a dose-dependent manner. The effect of rHDL on endothelial progenitor cells differentiation was abrogated by coadministration of LY294002, an inhibitor of phosphatidylinositol 3-kinase. rHDL failed to promote angiogenesis in endothelial NO–deficient mice.
CONCLUSIONS—rHDL directly stimulates endothelial progenitor cell differentiation via phosphatidylinositol 3-kinase/Akt pathway and enhances ischemia-induced angiogenesis. rHDL may be useful in the treatment of patients with ischemic cardiovascular diseases.</description><subject>Animals</subject><subject>Atherosclerosis (general aspects, experimental research)</subject><subject>Biological and medical sciences</subject><subject>Blood and lymphatic vessels</subject><subject>Blood vessels and receptors</subject><subject>Bone Marrow - pathology</subject><subject>Cardiology. Vascular system</subject><subject>Cardiovascular system</subject><subject>Cell Differentiation - drug effects</subject><subject>Cells, Cultured</subject><subject>Chimera</subject><subject>Collateral Circulation - drug effects</subject><subject>Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous</subject><subject>Endothelial Cells - pathology</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Hindlimb - blood supply</subject><subject>Humans</subject><subject>Ischemia - physiopathology</subject><subject>Lipoproteins, HDL - pharmacology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred Strains</subject><subject>Mice, Knockout</subject><subject>Neovascularization, Physiologic - drug effects</subject><subject>Nitric Oxide Synthase Type III - deficiency</subject><subject>Pharmacology. Drug treatments</subject><subject>Phosphatidylinositol 3-Kinases - metabolism</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>Regional Blood Flow - drug effects</subject><subject>Signal Transduction</subject><subject>Stem Cells - pathology</subject><subject>Vasodilator agents. Cerebral vasodilators</subject><subject>Vertebrates: cardiovascular system</subject><issn>1079-5642</issn><issn>1524-4636</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkc1uEzEUhUcIREvhFdAICXYz9f9kWCBFaaGRIoGgsLU8nuuMwbFT26Oq78BD4zaRsuV6cb34js_1PVX1DqMWY4EvEW6Xt79aVIrwnvR9SxcLRlvBnlXnmBPWMEHF83JHXd9wwchZ9Sql34VnhKCX1RnuSDmMnFd_v4MOPmWb5wxjfWO3U3MFPtn8UG_sPuxjyGB9_SPb3exUhlRfWWMggs9WZRt8HUx97ceQJ3BWufpbDFvwNodYr8C5VCs_FmBSXhfxOukJdlY1az_Oujgu_dY-CiDZ9Lp6YZRL8ObYL6qfn69vVzfN5uuX9Wq5aTTnlDUa6V4MYwdCG9ExxIUhqKOGM6EIDIbrXhkxcET7fiSKkoUahsEwhDs9soHTi-rD4d3yu7sZUpY7m3QZVnkIc5Idoogy3hXw4wHUMaQUwch9tDsVHyRG8jELibAsWchTFvIpCylYEb89uszDDsaT9Lj8Arw_Aipp5UwsK7LpxC0E5X1HC_fpwN0HlyGmP26-hygnUC5P_zPJP_H9qRw</recordid><startdate>200704</startdate><enddate>200704</enddate><creator>Sumi, Makoto</creator><creator>Sata, Masataka</creator><creator>Miura, Shin-ichiro</creator><creator>Rye, Kerry-Anne</creator><creator>Toya, Naoki</creator><creator>Kanaoka, Yuji</creator><creator>Yanaga, Katsuhiko</creator><creator>Ohki, Takao</creator><creator>Saku, Keijiro</creator><creator>Nagai, Ryozo</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>7X8</scope></search><sort><creationdate>200704</creationdate><title>Reconstituted High-Density Lipoprotein Stimulates Differentiation of Endothelial Progenitor Cells and Enhances Ischemia-Induced Angiogenesis</title><author>Sumi, Makoto ; Sata, Masataka ; Miura, Shin-ichiro ; Rye, Kerry-Anne ; Toya, Naoki ; Kanaoka, Yuji ; Yanaga, Katsuhiko ; Ohki, Takao ; Saku, Keijiro ; Nagai, Ryozo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5534-c0c96bd7e6cf674056f2073f546a2ebf5c9af6b50399d2a328abbbf4017cd4b53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Animals</topic><topic>Atherosclerosis (general aspects, experimental research)</topic><topic>Biological and medical sciences</topic><topic>Blood and lymphatic vessels</topic><topic>Blood vessels and receptors</topic><topic>Bone Marrow - pathology</topic><topic>Cardiology. Vascular system</topic><topic>Cardiovascular system</topic><topic>Cell Differentiation - drug effects</topic><topic>Cells, Cultured</topic><topic>Chimera</topic><topic>Collateral Circulation - drug effects</topic><topic>Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous</topic><topic>Endothelial Cells - pathology</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Hindlimb - blood supply</topic><topic>Humans</topic><topic>Ischemia - physiopathology</topic><topic>Lipoproteins, HDL - pharmacology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred Strains</topic><topic>Mice, Knockout</topic><topic>Neovascularization, Physiologic - drug effects</topic><topic>Nitric Oxide Synthase Type III - deficiency</topic><topic>Pharmacology. Drug treatments</topic><topic>Phosphatidylinositol 3-Kinases - metabolism</topic><topic>Proto-Oncogene Proteins c-akt - metabolism</topic><topic>Regional Blood Flow - drug effects</topic><topic>Signal Transduction</topic><topic>Stem Cells - pathology</topic><topic>Vasodilator agents. Cerebral vasodilators</topic><topic>Vertebrates: cardiovascular system</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sumi, Makoto</creatorcontrib><creatorcontrib>Sata, Masataka</creatorcontrib><creatorcontrib>Miura, Shin-ichiro</creatorcontrib><creatorcontrib>Rye, Kerry-Anne</creatorcontrib><creatorcontrib>Toya, Naoki</creatorcontrib><creatorcontrib>Kanaoka, Yuji</creatorcontrib><creatorcontrib>Yanaga, Katsuhiko</creatorcontrib><creatorcontrib>Ohki, Takao</creatorcontrib><creatorcontrib>Saku, Keijiro</creatorcontrib><creatorcontrib>Nagai, Ryozo</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>Arteriosclerosis, thrombosis, and vascular biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sumi, Makoto</au><au>Sata, Masataka</au><au>Miura, Shin-ichiro</au><au>Rye, Kerry-Anne</au><au>Toya, Naoki</au><au>Kanaoka, Yuji</au><au>Yanaga, Katsuhiko</au><au>Ohki, Takao</au><au>Saku, Keijiro</au><au>Nagai, Ryozo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Reconstituted High-Density Lipoprotein Stimulates Differentiation of Endothelial Progenitor Cells and Enhances Ischemia-Induced Angiogenesis</atitle><jtitle>Arteriosclerosis, thrombosis, and vascular biology</jtitle><addtitle>Arterioscler Thromb Vasc Biol</addtitle><date>2007-04</date><risdate>2007</risdate><volume>27</volume><issue>4</issue><spage>813</spage><epage>818</epage><pages>813-818</pages><issn>1079-5642</issn><eissn>1524-4636</eissn><coden>ATVBFA</coden><abstract>BACKGROUND—Plasma high-density lipoprotein (HDL) levels have an inverse correlation with incidence of ischemic heart disease as well as other atherosclerosis-related ischemic conditions. However, the molecular mechanism by which HDL prevents ischemic disease is not fully understood. Here, we investigated the effect of HDL on differentiation of endothelial progenitor cells and angiogenesis in murine ischemic hindlimb model.
METHODS AND RESULTS—Intravenous injection of reconstituted HDL (rHDL) significantly augmented blood flow recovery and increased capillary density in the ischemic leg. rHDL increased the number of bone marrow–derived cells incorporated into the newly formed capillaries in ischemic muscle. rHDL induced phosphorylation of Akt in human peripheral mononuclear cells. rHDL (50 to 100 μg apolipoprotein A-I/mL) promoted differentiation of peripheral mononuclear cells to endothelial progenitor cells in a dose-dependent manner. The effect of rHDL on endothelial progenitor cells differentiation was abrogated by coadministration of LY294002, an inhibitor of phosphatidylinositol 3-kinase. rHDL failed to promote angiogenesis in endothelial NO–deficient mice.
CONCLUSIONS—rHDL directly stimulates endothelial progenitor cell differentiation via phosphatidylinositol 3-kinase/Akt pathway and enhances ischemia-induced angiogenesis. rHDL may be useful in the treatment of patients with ischemic cardiovascular diseases.</abstract><cop>Philadelphia, PA</cop><cop>Hagerstown, MD</cop><pub>American Heart Association, Inc</pub><pmid>17272742</pmid><doi>10.1161/01.ATV.0000259299.38843.64</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Arteriosclerosis, thrombosis, and vascular biology, 2007-04, Vol.27 (4), p.813-818 |
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| subjects | Animals Atherosclerosis (general aspects, experimental research) Biological and medical sciences Blood and lymphatic vessels Blood vessels and receptors Bone Marrow - pathology Cardiology. Vascular system Cardiovascular system Cell Differentiation - drug effects Cells, Cultured Chimera Collateral Circulation - drug effects Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous Endothelial Cells - pathology Fundamental and applied biological sciences. Psychology Hindlimb - blood supply Humans Ischemia - physiopathology Lipoproteins, HDL - pharmacology Male Medical sciences Mice Mice, Inbred Strains Mice, Knockout Neovascularization, Physiologic - drug effects Nitric Oxide Synthase Type III - deficiency Pharmacology. Drug treatments Phosphatidylinositol 3-Kinases - metabolism Proto-Oncogene Proteins c-akt - metabolism Regional Blood Flow - drug effects Signal Transduction Stem Cells - pathology Vasodilator agents. Cerebral vasodilators Vertebrates: cardiovascular system |
| title | Reconstituted High-Density Lipoprotein Stimulates Differentiation of Endothelial Progenitor Cells and Enhances Ischemia-Induced Angiogenesis |
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