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Vascular adhesion protein-1 and microvascular diabetic complications

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Abstract

Vascular adhesion protein-1 (VAP-1) is a bifunctional protein that has the ability to catalyze the deamination of primary amines and is involved in the production of hydrogen peroxide, aldehydes, and advanced glycation end products (AGEs). VAP-1 is usually stored in intracellular vesicles of endothelial cells, smooth muscles, and adipocytes. It is responsible for leukocyte transmigration and adhesion. Overexpression of VAP-1 exacerbates oxidative stress and modulates a variety of inflammatory mediators linked with diabetic complications. Numerous studies have suggested the association of increased insulin levels with serum VAP-1 (sVAP-1). Preclinical research evidence suggests the increased activity of sVAP-1 in type 1 and 2 diabetes. Scientific reports on VAP-1 inhibitors have shown a reduction in severity in diabetic animal models. VAP-1 is a potential target of a therapeutically effective line of treatment for diabetes and diabetic complications such as nephropathy and retinopathy. The primary focus of this review is the role of VAP-1 in diabetes and its associated microvascular complications.

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Abbreviations

ACR:

Acrolein

AGE:

Advanced glycation end product

AOC/SSAO:

Amine oxidase/semicarbazide-sensitive amine oxidase

AOC:

Amine oxidase copper containing

AOC1:

Amine oxidase copper containing 1

AOC2:

Amine oxidase copper containing 2

AOC3:

Amine oxidase copper containing 3

AOC3KI:

AOC3 gene mutated

AOC3KO:

AOC3 gene knock-out

DM:

Diabetes mellitus

DR:

Diabetic retinopathy

ESRD:

End stage renal disease

FPG:

Fasting plasma glucose

GSH:

Glutathione

HEV:

High endothelial venules

ICAM-1:

Intercellular adhesion molecule-1

IDF:

International diabetes federation

IL-1β:

Interleukin 1-beta

IL-6:

Interleukin-6

LOX:

Lysyl oxidase

mAb:

Monoclonal antibody

MMP:

Matrix metalloproteinase

NADPH:

Nicotinamide adenine dinucleotide phosphate

NOD:

Non obese diabetic

PDR:

Proliferative diabetic retinopathy

sVAP-1:

Serum vascular adhesion protein-1

T2DM:

Type II diabetes mellitus

TNF-α:

Tumor necrosis factor-alpha

TPQ:

Topaquinone

VAP-1:

Vascular adhesion protein-1

VEGF:

Vascular endothelial growth factor

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  1. Shobhaben Pratapbhai Patel School of Pharmacy & Technology Management, SVKM’s NMIMS, V. L. Mehta Road, Vile Parle (W), Mumbai, Maharashtra, 400056, India

    Alok D. Singh & Yogesh A. Kulkarni

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The article was conceptualized by YK and AS. AS wrote the manuscript. YK and AS finalized the manuscript.

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Correspondence to Yogesh A. Kulkarni.

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Singh, A.D., Kulkarni, Y.A. Vascular adhesion protein-1 and microvascular diabetic complications. Pharmacol. Rep 74, 40–46 (2022). https://doi.org/10.1007/s43440-021-00343-y

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