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The vascular endothelin system in obesity and type 2 diabetes: pathophysiology and therapeutic implications. [Review] []

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Citation: Life Sciences. 118(2):149-55, 2014 Nov 24.PMID: 24607780Institution: MedStar Heart & Vascular InstituteForm of publication: Journal ArticleMedline article type(s): Journal Article | ReviewSubject headings: *Diabetes Mellitus, Type 2/pp [Physiopathology] | *Diabetes Mellitus, Type 2/th [Therapy] | *Endothelins/me [Metabolism] | *Endothelium, Vascular/me [Metabolism] | *Endothelium, Vascular/pa [Pathology] | *Obesity/pp [Physiopathology] | *Obesity/th [Therapy] | Adipose Tissue/pa [Pathology] | Animals | Diabetes Mellitus, Type 2/me [Metabolism] | Humans | Insulin Resistance | Obesity/me [Metabolism]Year: 2014 ISSN:

0024-3205

Name of journal: Life sciencesAbstract: Obesity, the metabolic syndrome (MetS), and type 2 diabetes (T2DM) are associated with heightened cardiovascular risk. Given the vasoconstrictor and proatherogenic properties of endothelin (ET)-1, increased ET-1 activity has been postulated to participate in the derangement of adiposity-related vascular homeostasis. This concept is supported by human studies using receptor antagonists to show that the activity of endogenous ET-1 is indeed enhanced in overweight and obesity, the MetS, and T2DM. Also, increased ET-1 contributes to endothelial dysfunction related to obesity, the MetS, and T2DM, whereas decreasing ET-1 vasoconstrictor tone in these patients corrects the defective endothelium-dependent vasodilation. In addition, in patients with central adiposity and the MetS, enhanced intravascular ET-1 activity coexists with decreased nitric oxide (NO)-dependent vasodilator capacity, suggesting a prevalence of vasoconstrictor mediators in vessels of obese individuals. One mechanism evoked to explain the development of vascular abnormalities in obesity deals with the derangement of the physiological vascular effects of insulin in insulin-resistant states. Thus, in conditions of adiposity, defective insulin-mediated vasodilation leads to impaired ability of the hormone to enhance its delivery and that of substrates to peripheral tissues. An important role of ET-1 in this abnormality is supported by studies showing that upregulation of the ET-1 system impairs NO-mediated vasodilation in insulin-resistant patients, whereas NO bioactivity is restored following ET-1 antagonism. In conclusion, considerable evidence supports a mechanistic role of ET-1 in the pathophysiology of adiposity-related vascular dysfunction. Targeting the ET-1 system, therefore, might have the potential for effective cardiovascular prevention in obesity, the MetS, and T2DM. Copyright � 2014 The Authors. Published by Elsevier Inc. All rights reserved.All authors: Campia U, Cardillo C, Di Daniele N, Tesauro MFiscal year: FY2015Digital Object Identifier:

http://dx.doi.org/10.1016/j.lfs.2014.02.028

Date added to catalog: 2016-01-13

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Item type	Current library	Collection	Call number	Status	Date due	Barcode
Journal Article	MedStar Authors Catalog	Article	24607780	Available		24607780

Obesity, the metabolic syndrome (MetS), and type 2 diabetes (T2DM) are associated with heightened cardiovascular risk. Given the vasoconstrictor and proatherogenic properties of endothelin (ET)-1, increased ET-1 activity has been postulated to participate in the derangement of adiposity-related vascular homeostasis. This concept is supported by human studies using receptor antagonists to show that the activity of endogenous ET-1 is indeed enhanced in overweight and obesity, the MetS, and T2DM. Also, increased ET-1 contributes to endothelial dysfunction related to obesity, the MetS, and T2DM, whereas decreasing ET-1 vasoconstrictor tone in these patients corrects the defective endothelium-dependent vasodilation. In addition, in patients with central adiposity and the MetS, enhanced intravascular ET-1 activity coexists with decreased nitric oxide (NO)-dependent vasodilator capacity, suggesting a prevalence of vasoconstrictor mediators in vessels of obese individuals. One mechanism evoked to explain the development of vascular abnormalities in obesity deals with the derangement of the physiological vascular effects of insulin in insulin-resistant states. Thus, in conditions of adiposity, defective insulin-mediated vasodilation leads to impaired ability of the hormone to enhance its delivery and that of substrates to peripheral tissues. An important role of ET-1 in this abnormality is supported by studies showing that upregulation of the ET-1 system impairs NO-mediated vasodilation in insulin-resistant patients, whereas NO bioactivity is restored following ET-1 antagonism. In conclusion, considerable evidence supports a mechanistic role of ET-1 in the pathophysiology of adiposity-related vascular dysfunction. Targeting the ET-1 system, therefore, might have the potential for effective cardiovascular prevention in obesity, the MetS, and T2DM. Copyright � 2014 The Authors. Published by Elsevier Inc. All rights reserved.