Impaired lipoprotein processing in hiv patients on antiretroviral therapy aberrant high-density lipoprotein lipids, stability, and function

Baiba K. Gillard, Joe L. Raya, Raul Ruiz-Esponda, Dinakar Iyer, Ivonne Coraza, Ashok Balasubramanyam, Henry J. Pownall

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Objective-HIV patients on antiretroviral therapy (HIV/ART) exhibit a unique atherogenic dyslipidemic profile with hypertriglyceridemia (HTG) and low plasma concentrations of high-density lipoprotein (HDL) cholesterol. In the Heart Positive Study of HIV/ART patients, a hypolipidemic therapy of fenofibrate, niacin, diet, and exercise reduced HTG and plasma non-HDL cholesterol concentrations and raised plasma HDL cholesterol and adiponectin concentrations. We tested the hypothesis that HIV/ART HDL have abnormal structures and properties and are dysfunctional. Approach and Results-Hypolipidemic therapy reduced the TG contents of low-density lipoprotein and HDL. At baseline, HIV/ART low-density lipoproteins were more triglyceride (TG)-rich and HDL were more TG- and cholesteryl esterrich than the corresponding lipoproteins from normolipidemic (NL) subjects. Very-low-density lipoproteins, lowdensity lipoprotein, and HDL were larger than the corresponding lipoproteins from NL subjects; HIV/ART HDL were less stable than NL HDL. HDL-[3H]cholesteryl ester uptake by Huh7 hepatocytes was used to assess HDL functionality. HIV/ART plasma were found to contain significantly less competitive inhibition activity for hepatocyte HDL-cholesteryl ester uptake than NL plasma were found to contain (P<0.001). Conclusions-Compared with NL subjects, lipoproteins from HIV/ART patients are larger and more neutral lipidrich, and their HDL are less stable and less receptor-competent. On the basis of this work and previous studies of lipase activity in HIV, we present a model in which plasma lipolytic activities or hepatic cholesteryl ester uptake are impaired in HIV/ART patients. These findings provide a rationale to determine whether the distinctive lipoprotein structure, properties, and function of HIV/ART HDL predict atherosclerosis as assessed by carotid artery intimal medial thickness.

Original languageEnglish (US)
Pages (from-to)1714-1721
Number of pages8
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume33
Issue number7
DOIs
StatePublished - Jul 2013

Keywords

  • Hepatocyte Cholesteryl Ester Uptake
  • High-Density Lipoprotein Function
  • Hiv Dyslipidemia
  • Lipoprotein Composition

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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