Low-density lipoprotein metabolism in cerebrotendinous xanthomatosis |
| |
| Authors: | C M Ballantyne G L Vega C East G Richards S M Grundy |
| |
| Affiliation: | 1. Department of Internal Medicine, University of Texas Health Science Center Dallas, USA.;2. Department of Biochemistry, University of Texas Health Science Center Dallas, USA.;3. the Center for Human Nutrition, University of Texas Health Science Center Dallas, USA.;1. Université Paris Cité, Paris, France;2. Department of Anaesthesiology and Surgical Intensive Care Unit, Groupe Hospitalier Bichat Claude Bernard, DMU PARABOL, Assistance Publique–Hôpitaux de Paris, Paris, France;3. Department of Anaesthesiology, Hôpital Louis Mourier, DMU PARABOL, Assistance Publique–Hôpitaux de Paris, Paris, France;4. AP-HP.Nord, Groupe Hospitalier Saint Louis Lariboisière, DMU PARABOL, Département d’anesthésie réanimation et centre de traitement des brûlés, Paris, France;5. Université Paris Cité, Centre de Recherche sur l’Inflammation, INSERM UMR 1149, CNRS ERL8252, Paris, France;6. Institut National de la Santé et de la Recherche Médicale (INSERM), INSERM UMR-S 942 Mascot, Lariboisière Hospital, Paris, France;7. INI-CRCT Network, Nancy, France;8. FHU PROMICE, Paris, France;9. AP-HP.Nord, Groupe Hospitalier Saint Louis Lariboisière, Laboratoire de Biochimie, Paris, France;10. AP-HP.Nord, Groupe Hospitalier Saint Louis Lariboisière, Département de radiologie, Paris, France;11. Department of Anesthesia and Peri-operative Care, Division of Critical Care Medicine, University of California, San Francisco, CA, USA;12. Assistance Publique–Hôpitaux de Paris (AP-HP), Groupe Hospitalier Cochin Port Royal, DMU Cancérologie et spécialités médico-chirurgicales, Service de Maladie du Foie, Paris, France;1. School of Health Sciences and Education, Department of Nutrition and Dietetics, Harokopio University, Athens, Greece;2. National and Kapodistrian University of Athens, School of Medicine, 1st Department of Psychiatry Eginition Hospital, Athens, Greece;3. Department of Psychiatry and Behavioral Sciences, Faculty of Medicine, University of Crete, Heraklion, Greece;4. Sleep Research and Treatment Center, Department of Psychiatry, Pennsylvania State University College of Medicine, USA;1. Division of Cardiology, Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea;2. Department of Medical Statistics, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea;3. Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea;1. College of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian 116600, PR China;2. Liaoning University of Traditional Chinese Medicine-Agilent Technologies Modern TCM and Multi-omics Research Collaboration Lab, Dalian 116600, PR China |
| |
| Abstract: | Cerebrotendinous xanthomatosis (CTX) is a rare disorder characterized by a defect in conversion of cholesterol into bile acids, increased plasma levels of cholestanol, and accumulations of sterols in tendons, brain, and coronary arteries. Despite the presence of tendon xanthomas, patients with CTX frequently have low levels of plasma cholesterol and low density lipoproteins (LDL). The mechanisms for a low LDL are not understood. The present study, therefore, was carried out to examine the metabolism of LDL in a 58-year-old black man with CTX. This particular patient had an LDL-cholesterol in the mid-normal range (149 +/- 6 mg/dL). Nonetheless, his fractional catabolic rate (FCR) for LDL-apolipoprotein (apo-LDL) was 0.45 pools/d, which was increased compared to 15 aged-matched men (FCR, 0.30 +/- 0.01 pools/d). His production rate for apo-LDL (18.5 mg/kg-d) also was increased compared to those of middle-aged men (13.5 +/- 2.5 mg/kg-d). Since the underlying defect in CTX can be reversed by administration of chenodeoxycholic acid (chenodiol), the patient was treated with chenodiol (250 mg 4X daily), and measurements of LDL kinetics were repeated. During chenodiol therapy, his LDL-cholesterol concentration rose significantly to 165 +/- 12 mg/dL; his FCR for apo-LDL fell to 0.29 pools/d; and his production rate of apo-LDL declined to 14.4 mg/kg-d. We postulate that chenodiol suppressed the excessive synthesis of cholesterol and bile acids, which had two effects. It curtailed both the overproduction of LDL and the excessive synthesis of LDL receptors, the latter being responsible for the high FCR of apo-LDL in the untreated state. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
