Coenzyme Q10 and diabetic endotheliopathy: oxidative stress and the 'recoupling hypothesis'.
Increased oxidative stress in diabetes mellitus may underlie the development of endothelial cell dysfunction by decreasing the availability of nitric oxide (NO) as well as by activating pro-inflammatory pathways. In the arterial wall, redox imbalance and oxidation of tetrahydrobiopterin (BH4) uncouples endothelial nitric oxide synthase (eNOS). This results in decreased production and increased consumption of NO, and generation of free radicals, such as superoxide and peroxynitrite. In the mitochondria, increased redox potential uncouples oxidative phosphorylation, resulting in inhibition of electron transport and increased transfer of electrons to molecular oxygen to form superoxide and other oxidant radicals. Coenzyme Q10 (CoQ), a potent antioxidant and a critical intermediate of the electron transport chain, may improve endothelial dysfunction by 'recoupling' eNOS and mitochondrial oxidative phosphorylation. CoQ supplementation may also act synergistically with anti-atherogenic agents, such as fibrates and statins, to improve endotheliopathy in diabetes.
Chew
G T
GT
School of Medicine and Pharmacology, University of Western Australia, Royal Perth Hospital Unit, GPO Box X2213, Perth, Western Australia, Australia 6847.
Watts
G F
GF
D000975:Antioxidants / Q000378:metabolism; D003067:Coenzymes; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000201:enzymology / Q000517:prevention & control; D003925:Diabetic Angiopathies / Q000188:drug therapy / Q000201:enzymology / Q000517:prevention & control; D019587:Dietary Supplements; D004357:Drug Synergism; D004730:Endothelium, Vascular / Q000201:enzymology; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III; D018384:Oxidative Stress / Q000502:physiology*; D010766:Phosphorylation; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014451:Ubiquinone / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000378:metabolism
D000975:Antioxidants; D003067:Coenzymes; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D014451:Ubiquinone; D009569:Nitric Oxide; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C024989:coenzyme Q10