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Table 3 The multiple metabolic toxicities of the A-FLIGHT-U acronym

From: Vascular ossification – calcification in metabolic syndrome, type 2 diabetes mellitus, chronic kidney disease, and calciphylaxis – calcific uremic arteriolopathy: the emerging role of sodium thiosulfate

Multiple injurious stimuli responsible for the production of ROS.

A

Angiotensin II (also induces protein kinase C – β isoform)

Amylin (hyperamylinemia) islet amyloid polypeptide toxicity

AGEs/AFEs (advanced glycosylation/fructosylation endproducts)

Apolipoprotein B

Antioxidant reserve compromised

Absence of antioxidant network

Aging

ADMA (Asymmetrical DiMethyl Arginine)

Adipose toxicity: Obesity toxicity – Lipid Triad (decreased HDL-C, increased triglycerides and small dense LDL-C)

Adipocytokine toxicity: Increased TNF alpha, Il-6, TGF beta, PAI-I and the increased hormones resistin, leptin and decreased adiponectin.

F

Free fatty acid toxicity: Obesity toxicity – Lipid Triad

L

Lipotoxicity – Hyperlipidemia – Obesity toxicity – Lipid Triad

Leptin toxicity

I

Insulin toxicity (endogenous hyperinsulinemia-hyperproinsulinemia)

IGF-1 – (GH-IGF-I axis) toxicity: This may serve to increase bone metabolism within the media of the AVW

Inflammation toxicity

G

Glucotoxicity (compounds peripheral insulin resistance) and induces reductive stress through the sorbitol/polyol pathway

Pseudohypoxia (increased NADH/NAD ratio)

H

Hypertension toxicity

Homocysteine toxicity

hs-CRP

T

Triglyceride toxicity: Obesity toxicity – Lipid Triad

U

Uric Acid – Xanthine Oxidase toxicity: Uric acid is an antioxidant early in physiological range of atherogenesis and a conditional prooxidant late when elevated through xanthine oxidase enzyme and generation of ROS: thus generating the paradoxical (antioxidant → prooxidant):

 

URATE REDOX SHUTTLE

 

Endothelial cell dysfunction with eNOS uncoupling, decreased eNO and increased

 

ROS