Alterations of Apolipoprotein B Metabolism in HIV-Infected Patients With Antiretroviral Combination Therapy
| Autor: | Johannes R. Bogner, Michaela Schmitz, Thomas Demant, Andrea Bedynek, Gerlinde M. Michl, Ravi Walli, Frank D. Goebel, Dietrich Seidel |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Adult
Male medicine.medical_specialty Very low-density lipoprotein Apolipoprotein B Anti-HIV Agents Lipoproteins HIV Infections Biology chemistry.chemical_compound Insulin resistance Internal medicine medicine Humans Pharmacology (medical) Apolipoproteins B Hypertriglyceridemia Triglyceride Cholesterol Middle Aged medicine.disease Kinetics Endocrinology Infectious Diseases chemistry biology.protein Reverse Transcriptase Inhibitors lipids (amino acids peptides and proteins) Drug Therapy Combination Insulin Resistance Dyslipidemia Lipoprotein |
| Zdroj: | JAIDS Journal of Acquired Immune Deficiency Syndromes. 26:225-235 |
| ISSN: | 1525-4135 |
| DOI: | 10.1097/00126334-200103010-00004 |
| Popis: | Background: Dyslipidemia (predominantly hypertriglyceridemia) is frequently seen in patients receiving antiretroviral combination therapy (ART). However, the underlying mechanisms and long-term risks (e.g., cardiovascular events) are still unclear. Objectives/Methods: In 5 patients with ART-associated dyslipidemia, stable isotope labeled amino acid tracer (d3-Leu) kinetic analysis over 12 days was used to investigate the metabolism of apolipoprotein B-containing lipoproteins (very low density lipoproteins [VLDL] 1 , VLDL 2 , intermediate density lipoproteins [IDL] and low density lipoproteins [LDL]). Data were compared with those in 6 healthy normolipidemic controls. Results: The patients under ART showed significantly increased fasting triglycerides (359 vs. 77 mg/dl) and VLDL (54 vs. 15 mg/dl), compared with controls. They had significantly higher total cholesterol (213 vs. 157 mg/dl) and there was a nonsignificant trend toward higher LDL (136 vs. 93 mg/dl), and toward lower HDL (26 vs. 46 mg/dl). The ratio of large, buoyant LDL 1 over small, dense LDL 2 was markedly reduced in patients under ART (0.80 vs. 2.00). Total apo B synthesis was significantly increased (25.5 vs. 14.5 mg/kg/d) and shifted toward triglyceride rich VLDL I (18.5 vs. 8.7 mg/kg/d) in patients receiving ART. There was also a significantly reduced rate of apo B lipoprotein transfer from VLDLI to VLDL2 (3.7 vs. 20.7 pools/d). In addition, all patients revealed insulin resistance. Conclusions: These data indicate that increased triglycerides in HIV-infected patients with ART are primary due to reduced rates of VLDL transfer into denser lipoproteins implying a lower rate of lipoprotein lipase-mediated delipidation. In addition, total apo B synthesis was increased and shifted toward triglyceride-rich VLDLI. Overall, this lipoprotein profile in patients with ART-associated dyslipidemia implies an increased risk for cardiovascular events. |
| Databáze: | OpenAIRE |
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