Cholestyramine Promotes Receptor-Mediated Low-Density-Lipoprotein Catabolism
We studied the influence of cholestyramine (24 g per day) on receptor-mediated and receptor-independent low-density-lipoprotein catabolism in five women with heterozygous familial hypercholesterolemia. Cholestyramine lowered the level of circulating low-density-lipoprotein apoprotein by doubling (P
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| Veröffentlicht in: | The New England journal of medicine 1980-05, Vol.302 (22), p.1219-1222 |
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| container_title | The New England journal of medicine |
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| creator | Shepherd, James Packard, Christopher J Bicker, Susan Lawrie, T. D. Veitch Morgan, H. Gemmell |
| description | We studied the influence of cholestyramine (24 g per day) on receptor-mediated and receptor-independent low-density-lipoprotein catabolism in five women with heterozygous familial hypercholesterolemia. Cholestyramine lowered the level of circulating low-density-lipoprotein apoprotein by doubling (P |
| doi_str_mv | 10.1056/NEJM198005293022202 |
| format | Article |
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CHOLESTYRAMINE (Questran, Mead Johnson) lowers plasma cholesterol
1
by sequestering bile acids in the gut and increasing their fecal excretion in both normal
2
and hypercholesterolemic subjects.
3
,
4
Although the drug produces subtle changes in high-density lipoprotein,
5
its hypocholesterolemic effect is achieved by a reduction
1
in the level of circulating low-density lipoprotein (LDL), whose fractional clearance rate from the plasma is increased by treatment.
6
Recent work by Goldstein and Brown has indicated at least two possible routes for LDL catabolism in cultured human cells.
7
One route involves initial binding of the lipoprotein to high-affinity cell-membrane receptors, and the other functions independently of the . . .</description><identifier>ISSN: 0028-4793</identifier><identifier>EISSN: 1533-4406</identifier><identifier>DOI: 10.1056/NEJM198005293022202</identifier><identifier>PMID: 7366673</identifier><language>eng</language><publisher>United States: Massachusetts Medical Society</publisher><subject>Adult ; Aged ; Atherosclerosis ; Biochemistry ; Cholesterol ; Cholesterol - blood ; Cholestyramine Resin - administration & dosage ; Cholestyramine Resin - pharmacology ; Cholestyramine Resin - therapeutic use ; Heterozygote ; Heterozygotes ; Humans ; Hypercholesterolemia ; Hyperlipoproteinemia Type II - blood ; Hyperlipoproteinemia Type II - drug therapy ; Hyperlipoproteinemia Type II - metabolism ; Iodine ; Lipids ; Lipoprotein receptors ; Lipoproteins, LDL - blood ; Lipoproteins, LDL - metabolism ; Low density lipoprotein ; Metabolism ; Middle Aged ; Receptor density ; Receptors, Drug - metabolism</subject><ispartof>The New England journal of medicine, 1980-05, Vol.302 (22), p.1219-1222</ispartof><rights>Copyright Massachusetts Medical Society May 29, 1980</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c403t-9816c575c46a86aa4fe5bdb8cf9d1e4c5cf6ff9f4e2c967aa438d4878a0053e52</citedby><cites>FETCH-LOGICAL-c403t-9816c575c46a86aa4fe5bdb8cf9d1e4c5cf6ff9f4e2c967aa438d4878a0053e52</cites></display><links><openurl>$$Topenurl_article</openurl><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>776</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/7366673$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shepherd, James</creatorcontrib><creatorcontrib>Packard, Christopher J</creatorcontrib><creatorcontrib>Bicker, Susan</creatorcontrib><creatorcontrib>Lawrie, T. D. Veitch</creatorcontrib><creatorcontrib>Morgan, H. Gemmell</creatorcontrib><title>Cholestyramine Promotes Receptor-Mediated Low-Density-Lipoprotein Catabolism</title><title>The New England journal of medicine</title><addtitle>N Engl J Med</addtitle><description>We studied the influence of cholestyramine (24 g per day) on receptor-mediated and receptor-independent low-density-lipoprotein catabolism in five women with heterozygous familial hypercholesterolemia. Cholestyramine lowered the level of circulating low-density-lipoprotein apoprotein by doubling (P<0.01) its fractional clearance via the receptor path, but fractional catabolism by the receptor-independent route remained unchanged. Moreover, although the absolute rate of catabolism of the apoprotein was not affected by treatment, the amounts handled by each pathway altered. Catabolism via the physiologically controllable receptor route increased by 71 per cent (P<0.05), but there was a 12 per cent drop in clearance by the nonreceptor pathway. These data demonstrate the utility of cholestyramine in promoting low-density-lipoprotein catabolism via its specific physiologic clearance pathway. They also show that heterozygotes with familial hypercholesterolemia can increase the activity of their low-density-lipoprotein receptors when presented with an appropriate stimulus. (N Engl J Med. 1980; 302: 1219–22.)
CHOLESTYRAMINE (Questran, Mead Johnson) lowers plasma cholesterol
1
by sequestering bile acids in the gut and increasing their fecal excretion in both normal
2
and hypercholesterolemic subjects.
3
,
4
Although the drug produces subtle changes in high-density lipoprotein,
5
its hypocholesterolemic effect is achieved by a reduction
1
in the level of circulating low-density lipoprotein (LDL), whose fractional clearance rate from the plasma is increased by treatment.
6
Recent work by Goldstein and Brown has indicated at least two possible routes for LDL catabolism in cultured human cells.
7
One route involves initial binding of the lipoprotein to high-affinity cell-membrane receptors, and the other functions independently of the . . .</description><subject>Adult</subject><subject>Aged</subject><subject>Atherosclerosis</subject><subject>Biochemistry</subject><subject>Cholesterol</subject><subject>Cholesterol - blood</subject><subject>Cholestyramine Resin - administration & dosage</subject><subject>Cholestyramine Resin - pharmacology</subject><subject>Cholestyramine Resin - therapeutic use</subject><subject>Heterozygote</subject><subject>Heterozygotes</subject><subject>Humans</subject><subject>Hypercholesterolemia</subject><subject>Hyperlipoproteinemia Type II - blood</subject><subject>Hyperlipoproteinemia Type II - drug therapy</subject><subject>Hyperlipoproteinemia Type II - metabolism</subject><subject>Iodine</subject><subject>Lipids</subject><subject>Lipoprotein receptors</subject><subject>Lipoproteins, LDL - blood</subject><subject>Lipoproteins, LDL - metabolism</subject><subject>Low density lipoprotein</subject><subject>Metabolism</subject><subject>Middle Aged</subject><subject>Receptor density</subject><subject>Receptors, Drug - metabolism</subject><issn>0028-4793</issn><issn>1533-4406</issn><fulltext>false</fulltext><rsrctype>article</rsrctype><creationdate>1980</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BEC</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp9kEtLw0AUhQdRaq3-AhEKghuJzmSeWUqtL1IV0XWYTG4wJZOpMwnSf-9IiwsR7-Yu7ncO5x6Ejgm-IJiLy8f5w4JkCmOeZhSnaYrTHTQmnNKEMSx20RjjVCVMZnQfHYSwxHEIy0ZoJKkQQtIxymfvroXQr722TQfTZ--s6yFMX8DAqnc-WUDV6B6qae4-k2voQtOvk7xZuZWPYNNNZ7rXpWubYA_RXq3bAEfbPUFvN_PX2V2SP93ez67yxDBM-yRTRBguuWFCK6E1q4GXValMnVUEmOGmFnWd1QxSkwkZAaoqpqTS8VUKPJ2gs41vjPAxxPSFbYKBttUduCEUkmOFCVERPP0FLt3gu5itIEooKRlnIlJ0QxnvQvBQFyvfWO3XBcHFd9PFH01H1cnWeygtVD-abbXxfr65WxuKDpb2X7cv5YSFVg</recordid><startdate>19800529</startdate><enddate>19800529</enddate><creator>Shepherd, James</creator><creator>Packard, Christopher J</creator><creator>Bicker, Susan</creator><creator>Lawrie, T. D. Veitch</creator><creator>Morgan, H. 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D. Veitch ; Morgan, H. Gemmell</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c403t-9816c575c46a86aa4fe5bdb8cf9d1e4c5cf6ff9f4e2c967aa438d4878a0053e52</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1980</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Atherosclerosis</topic><topic>Biochemistry</topic><topic>Cholesterol</topic><topic>Cholesterol - blood</topic><topic>Cholestyramine Resin - administration & dosage</topic><topic>Cholestyramine Resin - pharmacology</topic><topic>Cholestyramine Resin - therapeutic use</topic><topic>Heterozygote</topic><topic>Heterozygotes</topic><topic>Humans</topic><topic>Hypercholesterolemia</topic><topic>Hyperlipoproteinemia Type II - blood</topic><topic>Hyperlipoproteinemia Type II - drug therapy</topic><topic>Hyperlipoproteinemia Type II - metabolism</topic><topic>Iodine</topic><topic>Lipids</topic><topic>Lipoprotein receptors</topic><topic>Lipoproteins, LDL - blood</topic><topic>Lipoproteins, LDL - metabolism</topic><topic>Low density lipoprotein</topic><topic>Metabolism</topic><topic>Middle Aged</topic><topic>Receptor density</topic><topic>Receptors, Drug - metabolism</topic><toplevel>peer_reviewed</toplevel><creatorcontrib>Shepherd, James</creatorcontrib><creatorcontrib>Packard, Christopher J</creatorcontrib><creatorcontrib>Bicker, Susan</creatorcontrib><creatorcontrib>Lawrie, T. 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D. Veitch</au><au>Morgan, H. Gemmell</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cholestyramine Promotes Receptor-Mediated Low-Density-Lipoprotein Catabolism</atitle><jtitle>The New England journal of medicine</jtitle><addtitle>N Engl J Med</addtitle><date>1980-05-29</date><risdate>1980</risdate><volume>302</volume><issue>22</issue><spage>1219</spage><epage>1222</epage><pages>1219-1222</pages><issn>0028-4793</issn><eissn>1533-4406</eissn><abstract>We studied the influence of cholestyramine (24 g per day) on receptor-mediated and receptor-independent low-density-lipoprotein catabolism in five women with heterozygous familial hypercholesterolemia. Cholestyramine lowered the level of circulating low-density-lipoprotein apoprotein by doubling (P<0.01) its fractional clearance via the receptor path, but fractional catabolism by the receptor-independent route remained unchanged. Moreover, although the absolute rate of catabolism of the apoprotein was not affected by treatment, the amounts handled by each pathway altered. Catabolism via the physiologically controllable receptor route increased by 71 per cent (P<0.05), but there was a 12 per cent drop in clearance by the nonreceptor pathway. These data demonstrate the utility of cholestyramine in promoting low-density-lipoprotein catabolism via its specific physiologic clearance pathway. They also show that heterozygotes with familial hypercholesterolemia can increase the activity of their low-density-lipoprotein receptors when presented with an appropriate stimulus. (N Engl J Med. 1980; 302: 1219–22.)
CHOLESTYRAMINE (Questran, Mead Johnson) lowers plasma cholesterol
1
by sequestering bile acids in the gut and increasing their fecal excretion in both normal
2
and hypercholesterolemic subjects.
3
,
4
Although the drug produces subtle changes in high-density lipoprotein,
5
its hypocholesterolemic effect is achieved by a reduction
1
in the level of circulating low-density lipoprotein (LDL), whose fractional clearance rate from the plasma is increased by treatment.
6
Recent work by Goldstein and Brown has indicated at least two possible routes for LDL catabolism in cultured human cells.
7
One route involves initial binding of the lipoprotein to high-affinity cell-membrane receptors, and the other functions independently of the . . .</abstract><cop>United States</cop><pub>Massachusetts Medical Society</pub><pmid>7366673</pmid><doi>10.1056/NEJM198005293022202</doi><tpages>4</tpages></addata></record> |
| fulltext | no_fulltext |
| identifier | ISSN: 0028-4793 |
| ispartof | The New England journal of medicine, 1980-05, Vol.302 (22), p.1219-1222 |
| issn | 0028-4793 1533-4406 |
| language | eng |
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| subjects | Adult Aged Atherosclerosis Biochemistry Cholesterol Cholesterol - blood Cholestyramine Resin - administration & dosage Cholestyramine Resin - pharmacology Cholestyramine Resin - therapeutic use Heterozygote Heterozygotes Humans Hypercholesterolemia Hyperlipoproteinemia Type II - blood Hyperlipoproteinemia Type II - drug therapy Hyperlipoproteinemia Type II - metabolism Iodine Lipids Lipoprotein receptors Lipoproteins, LDL - blood Lipoproteins, LDL - metabolism Low density lipoprotein Metabolism Middle Aged Receptor density Receptors, Drug - metabolism |
| title | Cholestyramine Promotes Receptor-Mediated Low-Density-Lipoprotein Catabolism |
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