Vascular endothelium dysfunction: a conservative target in metabolic disorders

Aim Vascular endothelium plays a role in capillary transport of nutrients and drugs and regulates angiogenesis, homeostasis, as well as vascular tone and permeability as a major regulator of local vascular homeostasis. The present study has been designed to investigate the role of endothelium in met...

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Bibliographic Details
Published in:Inflammation research Vol. 67; no. 5; pp. 391 - 405
Main Authors: Jamwal, Shalini, Sharma, Saurabh
Format: Journal Article
Language:English
Published: Cham Springer International Publishing 01.05.2018
Springer Nature B.V
Subjects:
Aldehyde reductase
Allergology
Angiogenesis
Angiotensin
Angiotensin II
Animals
Anions
Arginine
Bioavailability
Biomedical and Life Sciences
Biomedicine
Cardiovascular Diseases - physiopathology
Cardiovascular Diseases - therapy
Cholesterol
Cytokines
Dephosphorylation
Dermatology
Diabetes
Diabetes mellitus
Disorders
Drugs
Endothelium
Endothelium, Vascular - physiopathology
Glycosylation
Homeostasis
Homocysteine
Humans
Hypercholesterolemia
Hyperhomocysteinemia
Hypertension
Immunology
Inflammation
Kinases
Metabolic Diseases - complications
Metabolic Diseases - therapy
Metabolic disorders
Molecular modelling
Monomethyl-L-arginine
Neurology
Nitric oxide
Nutrients
Oxidation
Oxidative stress
Permeability
Peroxides
Pharmacology/Toxicology
Phosphorylation
Prostaglandins
Protein kinase
Reactive oxygen species
Review
Rheumatology
Vascular Diseases - etiology
Vascular Diseases - physiopathology
Vascular Diseases - therapy
Vasoconstriction
Vasodilation
Xanthine oxidase
Vascular endothelial dysfunction
Hypertension
Endothelial
Oxidative stress
Cardiovascular disease
Nitric oxide
ISSN:1023-3830, 1420-908X, 1420-908X
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Summary:Aim Vascular endothelium plays a role in capillary transport of nutrients and drugs and regulates angiogenesis, homeostasis, as well as vascular tone and permeability as a major regulator of local vascular homeostasis. The present study has been designed to investigate the role of endothelium in metabolic disorders. Methods The endothelium maintains the balance between vasodilatation and vasoconstriction, procoagulant and anticoagulant, prothrombotic and antithrombotic mechanisms. Results Diabetes mellitus causes the activation of aldose reductase, polyol pathway and advanced glycation-end-product formation that collectively affect the phosphorylation status and expression of endothelial nitric oxide synthatase (eNOS) and causes vascular endothelium dysfunction. Elevated homocysteine levels have been associated with increase in LDL oxidation, generation of hydrogen peroxides, superoxide anions that increased oxidative degradation of nitric oxide. Hyperhomocysteinemia has been reported to increase the endogenous competitive inhibitors of eNOS viz L-N-monomethyl arginine (L-NMMA) and asymmetric dimethyl arginine (ADMA) that may contribute to vascular endothelial dysfunction. Hypercholesterolemia stimulates oxidation of LDL cholesterol, release of endothelins, and generation of ROS. The increased cholesterol and triglyceride level and decreased protective HDL level, decreases the activity and expression of eNOS and disrupts the integrity of vascular endothelium, due to oxidative stress. Hypertension also stimulates release of endothelins, vasoconstrictor prostanoids, angiotensin II, inflammatory cytokines, xanthine oxidase and, thereby, reduces bioavailability of nitric oxide. Conclusion Thus, the cellular and molecular mechanisms underlying diabetes mellitus, hyperhomocysteinemia, hypercholesterolemia hypertension and hyperuricemia leads to an imbalance of phosphorylation and dephosphorylation status of lipid and protein kinase that cause modulation of vascular endothelial L-arginine/nitric oxide synthetase (eNOS), to produce vascular endothelium dysfunction.
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ISSN:1023-3830
1420-908X
1420-908X
DOI:10.1007/s00011-018-1129-8