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A defect in the activity of Delta6 and Delta5 desaturases may be a factor in the initiation and progression of atherosclerosis.
Prostaglandins Leukot Essent Fatty Acids. 2007 May; 76(5):251-68.PL

Abstract

Atherosclerosis is a dynamic process. Dyslipidemia, diabetes mellitus, hypertension, obesity, and shear stress of blood flow, the risk factors for the development of atherosclerosis, are characterized by abnormalities in the metabolism of essential fatty acids (EFAs). Gene expression profiling studies revealed that at the sites of atheroslcerosis-prone regions, endothelial cells showed upregulation of pro-inflammatory genes as well as antioxidant genes, and endothelial cells themselves showed changes in cell shape and proliferation. Uncoupled respiration (UCP-1) precedes atherosclerosis at lesion-prone sites but not at the sites that are resistant to atherosclerosis. UCP-1 expression in aortic smooth muscle cells causes hypertension, enhanced superoxide anion production and decreased the availability of NO, suggesting that inefficient metabolism in blood vessels causes atherosclerosis without affecting cholesterol levels. Thus, mitochondrial dysfunction triggers atherosclerosis. Atherosclerosis-free aortae have abundant concentrations of the EFA-linoleate, whereas fatty streaks (an early stage of atherosclerosis) are deficient in EFAs. EFA deficiency promotes respiratory uncoupling and atherosclerosis. I propose that a defect in the activity of Delta6 and Delta5 desaturases decreases the formation of gamma-linolenic acid (GLA), dihomo-DGLA (DGLA), arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) from dietary linoleic acid (LA) and alpha-linolenic acid (ALA). This, in turn, leads to inadequate formation of prostaglandin E1 (PGE1), prostacyclin (PGI2), PGI3, lipoxins (LXs), resolvins, neuroprotectin D1 (NPD1), NO, and nitrolipids that have anti-inflammatory and platelet anti-aggregatory actions, inhibit leukocyte activation and augment wound healing and resolve inflammation and thus, lead to the initiation and progression atheroslcerosis. In view of this, it is suggested that Delta6 and Delta5 desaturases could serve as biological target(s) for the discovery and development of pharmaceuticals to treat atherosclerosis.

Authors+Show Affiliations

UND Life Sciences, Shaker Heights, OH 44120, USA.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

17466497

Citation

Das, Undurti N.. "A Defect in the Activity of Delta6 and Delta5 Desaturases May Be a Factor in the Initiation and Progression of Atherosclerosis." Prostaglandins, Leukotrienes, and Essential Fatty Acids, vol. 76, no. 5, 2007, pp. 251-68.
Das UN. A defect in the activity of Delta6 and Delta5 desaturases may be a factor in the initiation and progression of atherosclerosis. Prostaglandins Leukot Essent Fatty Acids. 2007;76(5):251-68.
Das, U. N. (2007). A defect in the activity of Delta6 and Delta5 desaturases may be a factor in the initiation and progression of atherosclerosis. Prostaglandins, Leukotrienes, and Essential Fatty Acids, 76(5), 251-68.
Das UN. A Defect in the Activity of Delta6 and Delta5 Desaturases May Be a Factor in the Initiation and Progression of Atherosclerosis. Prostaglandins Leukot Essent Fatty Acids. 2007;76(5):251-68. PubMed PMID: 17466497.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A defect in the activity of Delta6 and Delta5 desaturases may be a factor in the initiation and progression of atherosclerosis. A1 - Das,Undurti N, Y1 - 2007/04/26/ PY - 2007/01/07/received PY - 2007/03/07/accepted PY - 2007/5/1/pubmed PY - 2007/9/18/medline PY - 2007/5/1/entrez SP - 251 EP - 68 JF - Prostaglandins, leukotrienes, and essential fatty acids JO - Prostaglandins Leukot Essent Fatty Acids VL - 76 IS - 5 N2 - Atherosclerosis is a dynamic process. Dyslipidemia, diabetes mellitus, hypertension, obesity, and shear stress of blood flow, the risk factors for the development of atherosclerosis, are characterized by abnormalities in the metabolism of essential fatty acids (EFAs). Gene expression profiling studies revealed that at the sites of atheroslcerosis-prone regions, endothelial cells showed upregulation of pro-inflammatory genes as well as antioxidant genes, and endothelial cells themselves showed changes in cell shape and proliferation. Uncoupled respiration (UCP-1) precedes atherosclerosis at lesion-prone sites but not at the sites that are resistant to atherosclerosis. UCP-1 expression in aortic smooth muscle cells causes hypertension, enhanced superoxide anion production and decreased the availability of NO, suggesting that inefficient metabolism in blood vessels causes atherosclerosis without affecting cholesterol levels. Thus, mitochondrial dysfunction triggers atherosclerosis. Atherosclerosis-free aortae have abundant concentrations of the EFA-linoleate, whereas fatty streaks (an early stage of atherosclerosis) are deficient in EFAs. EFA deficiency promotes respiratory uncoupling and atherosclerosis. I propose that a defect in the activity of Delta6 and Delta5 desaturases decreases the formation of gamma-linolenic acid (GLA), dihomo-DGLA (DGLA), arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) from dietary linoleic acid (LA) and alpha-linolenic acid (ALA). This, in turn, leads to inadequate formation of prostaglandin E1 (PGE1), prostacyclin (PGI2), PGI3, lipoxins (LXs), resolvins, neuroprotectin D1 (NPD1), NO, and nitrolipids that have anti-inflammatory and platelet anti-aggregatory actions, inhibit leukocyte activation and augment wound healing and resolve inflammation and thus, lead to the initiation and progression atheroslcerosis. In view of this, it is suggested that Delta6 and Delta5 desaturases could serve as biological target(s) for the discovery and development of pharmaceuticals to treat atherosclerosis. SN - 0952-3278 UR - https://www.unboundmedicine.com/medline/citation/17466497/A_defect_in_the_activity_of_Delta6_and_Delta5_desaturases_may_be_a_factor_in_the_initiation_and_progression_of_atherosclerosis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0952-3278(07)00037-3 DB - PRIME DP - Unbound Medicine ER -