Title:Targeting Mitochondrial Oxidative Stress Through Lipoic Acid Synthase: A Novel Strategy to Manage Diabetic Cardiovascular Disease
Volume: 10
Issue: 3
Author(s): Indira Padmalayam
Affiliation:
Keywords:
Antioxidant, atherosclerosis, cardiovascular disease, catalase, diabetes, electron transport chain, free radicals,
glutathione, inflammation, insulin resistance, lipoic acid, mitochondrial function, oxidative stress, pyruvate dehydrogenase, ROS, superoxide dismutase
Abstract: Mitochondrial oxidative stress is a major etiological factor in the development of cardiovascular disease
associated with type 2 diabetes. Hyperglycemia and insulin resistance contribute to the generation of excessive reactive
oxygen species (ROS) which have damaging effects on various macromolecules within the mitochondria, leading to
mitochondrial dysfunction. Mitochondrial damage within the endothelial cells lining the vasculature causes endothelial
dysfunction, a critical event in atherosclerosis. In diabetes, deficiency of the antioxidant defense network prevents the
generation of a robust response to counter the damaging effects of ROS. Since oxidative stress is the underlying factor for
the damages inflicted by hyperglycemia, a logical therapeutic approach is to use antioxidants to quench ROS produced
within the mitochondria. Lipoic acid (LA) is a potent mitochondrial antioxidant and an essential cofactor of α-ketoacid
dehydrogenases. Clinical studies testing the effects of LA supplementation in diabetes and its complications have yielded
promising results, especially with regard to management of diabetic neuropathy. Endogenously, LA is synthesized within
the mitochondria by the enzyme, Lipoic acid synthase (LASY). This review describes a novel therapeutic approach which
is aimed at increasing expression of LASY to enhance mitochondrial levels of LA. Such a strategy has the potential of
improving mitochondrial function, reducing inflammation and insulin resistance, translating to better metabolic control in
diabetes and preventing cardiovascular disease.
