Dual Roles for Lipolysis and Oxidation in Peroxisome Proliferation-Activator Receptor Responses to Electronegative Low Density Lipoprotein

Ziouzenkova, Ouliana; Asatryan, Liana; Sahady, Deanna; Orasanu, Gabriela; Perrey, S.; Cutak, Benjamin J.; Hassell, Tom; Akiyama, Taro E.; Berger, Joel P.; Sevanian, Alex; Plutzky, Jorge

doi:10.1074/jbc.m306786200

Cited by 60 publications

(45 citation statements)

References 39 publications

(57 reference statements)

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“…If this postulated mechanism is correct, the results indicate the presence of large amounts of some oxylipids in glycerides circulating in lipoproteins. Many other investigators have found significant amounts of esterified oxylipids in lipoproteins, and their presence has been postulated to play a role in atherogenesis [7][8][9]. The susceptibility of various oxylipid esters to various lipases has not been published, and we do not know what proportion of total esterified oxylipids was liberated during our experiment.…”

Section: Discussionmentioning

confidence: 73%

Heparin, lipoproteins, and oxygenated fatty acids in blood: A cautionary note

Goodfriend¹,

Pedersen²,

Grekin³

et al. 2007

Prostaglandins, Leukotrienes and Essential Fatty Acids

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We measured 16 nonesterified oxygenated fatty acid derivatives (oxylipids) in plasmas from 7 human subjects. Two arterial samples from each subject were analyzed, drawn approximately two hours apart. We observed a marked increase in levels of most oxylipids in the second sample, as high as 470 fold. Between the first and second sample, subjects received approximately 800-1,000 IU of heparin to prevent clotting in intravascular catheters. We postulate that heparin activated lipoprotein lipases, which, in turn, released oxylipids from triglycerides and phospholipids in plasma lipoproteins. Some of that lipolysis may have occurred during sample storage. Measurements of nonesterified lipids in human plasma may be distorted if heparin is administered to subjects before blood is drawn and if lipase inhibitors are omitted from stored samples.

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Section: Discussionmentioning

confidence: 73%

Heparin, lipoproteins, and oxygenated fatty acids in blood: A cautionary note

Goodfriend¹,

Pedersen²,

Grekin³

et al. 2007

Prostaglandins, Leukotrienes and Essential Fatty Acids

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“…Fatty acids produced by LPL hydrolysis of VLDL (and to a lesser extent LDL and HDL) activate PPAR␣ and thus reverse the increase in vascular cell adhesion molecule-1 expression induced by inflammatory stimuli such as TNF-␣ and lipoproteins (65). In addition to highlighting a novel anti-inflammatory pathway, these findings suggest different transcriptional responses dependent on the specific mechanism of fatty acid generation and uptake (66).…”

Section: Potential Therapeutic Roles Of Ppar Agonists In Other Vasculmentioning

confidence: 84%

Therapeutic Roles of Peroxisome Proliferator–Activated Receptor Agonists

2005

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Peroxisome proliferator-activated receptors (PPARs) play key roles in the regulation of energy homeostasis and inflammation, and agonists of PPAR␣ and -␥ are currently used therapeutically. Fibrates, first used in the 1970s for their lipid-modifying properties, were later shown to activate PPAR␣. These agents lower plasma triglycerides and VLDL particles and increase HDL cholesterol, effects that are associated with cardiovascular benefit. Thiazolidinediones, acting via PPAR␥, influence free fatty acid flux and thus reduce insulin resistance and blood glucose levels. PPAR␥ agonists are therefore used to treat type 2 diabetes. PPAR␣ and -␥ agonists also affect inflammation, vascular function, and vascular remodeling. As knowledge of the pleiotropic effects of these agents advances, further potential indications are being revealed, including roles in the management of cardiovascular disease (CVD) and the metabolic syndrome. Dual PPAR␣/␥ agonists (currently in development) look set to combine the properties of thiazolidinediones and fibrates, and they hold considerable promise for improving the management of type 2 diabetes and providing an effective therapeutic option for treating the multifactorial components of CVD and the metabolic syndrome. The functions of a third PPAR isoform, PPAR␦, and its potential as a therapeutic target are currently under investigation.

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“…Previous studies have shown that LPL in combination with either triglyceride-rich lipoprotein or electronegative low density lipoproteins suppressed TNF-␣-induced cell surface adhesion molecule (VCAM-1) expression through peroxisome proliferator-activated receptor-␣ inhibition of NF-B activity (35,36). Peroxisome proliferator-activated receptor ligands are involved in anti-inflammatory effects (37,38).…”

Section: Discussionmentioning

confidence: 99%