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Vascular endothelium dysfunction: a conservative target in metabolic disorders

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Abstract

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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Authors and Affiliations

  1. Department of Pharmacology, I.S.F College of Pharmacy, Moga, 142001, Punjab, India

    Shalini Jamwal

  2. Department of Pharmacology, School of Pharmaceutical Sciences, CT University, Ludhiana, Punjab, India

    Saurabh Sharma

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  1. Shalini Jamwal
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  2. Saurabh Sharma
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Correspondence to Saurabh Sharma.

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Responsible Editor: Bernhard Gibbs.

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Jamwal, S., Sharma, S. Vascular endothelium dysfunction: a conservative target in metabolic disorders. Inflamm. Res. 67, 391–405 (2018). https://doi.org/10.1007/s00011-018-1129-8

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  • DOI: https://doi.org/10.1007/s00011-018-1129-8

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