|
The multiple metabolic toxicities of the A-FLIGHT-U acronym |
|
| 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 |
|
Hayden et al. Cardiovascular Diabetology 2005 4:4 doi:10.1186/1475-2840-4-4 |
|