Table 1 A-FLIGHT-U ACRONYM Identification of multiple metabolic toxicities and injurious stimuli responsible for reactive oxygen species production. (figure 2)

A

Angiotensin II (also induces PKC-β isoform)

Amylin (hyperamylinemia) / amyloid toxicity

AGEs/AFEs (advanced glycosylation/fructosylation endproducts)

Apolipoprotein B

Antioxidant reserve compromised

Absence of antioxidant network

Aging

ADMA (Asymmetrical DiMethyl Arginine)

F

Free fatty acid toxicity: Obesity toxicity: Triad

L

Lipotoxicity – Hyperlipidemia – Obesity toxicity: Triad

I

Insulin toxicity (endogenous hyperinsulinemia-hyperproinsulinemia)

Inflammation toxicity

G

Glucotoxicity (compounds peripheral insulin resistance) reductive stress

Sorbitol/polyol pathway

Pseudohypoxia (increased NADH/NAD ratio)

H

Hypertension toxicity

Homocysteine toxicity

hs-CRP

T

Triglyceride toxicity: Obesity toxicity: Triad

U

Uric Acid toxicity: Antioxidant early in physiological range and a conditional prooxidant late when elevated through the paradoxical (antioxidant → prooxidant)

Endothelial cell dysfunction with eNOS uncoupling, decreased eNO and increased ROS.

Vulnerable atherosclerotic plaque milieu of being acidic, proinflammatory, excess metal ions (Fe) (Cu) from vasa vasorum rupture and red blood cell plasma membranes due to intraplaque hemorrhage and plaque thrombus formation.