Hydroxyoctadecadienoic acids: novel regulators of macrophage differentiation and atherogenesis

Vangaveti, Venkat, Baune, Bernhard T., and Kennedy, R. Lee (2010) Hydroxyoctadecadienoic acids: novel regulators of macrophage differentiation and atherogenesis. Therapeutic Advances in Endocrinology and Metabolism, 1 (2). pp. 51-60.

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Abstract

Hydroxyoctadecadienoic acids (HODEs) are stable oxidation products of linoleic acid, the generation of which is increased where oxidative stress is increased, such as in diabetes. In early atherosclerosis, 13-HODE is generated in macrophages by 15-lipoxygenase-1. This enhances protective mechanisms through peroxisome proliferator-activated receptor (PPAR)-γ activation leading to increased clearance of lipid and lipid-laden cells from the arterial wall. In later atherosclerosis, both 9-HODE and 13-HODE are generated nonenzymatically. At this stage, early protective mechanisms are overwhelmed and pro-inflammatory effects of 9-HODE, acting through the receptor GPR132, and increased apoptosis predominate leading to a fragile, acellular plaque. Increased HODE levels thus contribute to atherosclerosis progression and the risk of clinical events such as myocardial infarction or stroke. Better understanding of the role of HODEs may lead to new pharmacologic approaches to modulate their production or action, and therefore lessen the burden of atherosclerotic disease in high-risk patients.

Item ID: 11732
Item Type: Article (Refereed Research - C1)
Keywords: atherosclerosis; diabetes; oxidative stress; oxidized lipids; G protein-coupled receptors
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ISSN: 2042-0196
Date Deposited: 09 Aug 2010 05:46
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1115 Pharmacology and Pharmaceutical Sciences > 111502 Clinical Pharmacology and Therapeutics @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920104 Diabetes @ 100%
Citation Count from Scopus Scopus 7
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