title: Oxidative stress and endothelial dysfunction in cardiovascular disease: mitochondria-targeted therapeutics.
abstract: Functional impairment of endothelial activity (endothelial dysfunction) precedes the development of cardiovascular diseases (CVD). This condition is a result of a reduced bioavailability of nitric oxide (NO), a well known vasodilator, which is mainly due to increased NO degradation caused by its reaction with reactive oxygen species (ROS). Although there are several conditions that contribute independently to endothelial dysfunction, such as hyperglycemia, insulin resistance, hyperinsulinemia and dyslipidemia, increased oxidative stress seems to play a key role. In addition to their original pharmacological properties, drugs used clinically at present, including anti-hypertension reagents, angiotensin receptor blockers and anti-hyperlipidemic reagents such as statins, protect various organs via anti-oxidative stress mechanisms. Moreover, some substances with antioxidant properties, such as vitamin C or vitamin E, have been used to eradicate the oxidative stress associated with CVD. The results of the clinical trials employing anti-oxidative stress reagents in patients with CVD are contradictory, which could be a result of inadequate study design or selected targets. This review considers the process of endothelial dysfunction and CVD from a mitochondrial perspective and evaluates strategies currently under development for the targeted delivery of antioxidants or NO to mitochondria. It endorses the idea that selectively targeting specific antioxidants and NO donors to mitochondria is an effective strategy for modulating mitochondrial respiration and ROS production and protecting mitochondria against oxidative stress.
authors.affiliation: University Hospital Doctor Peset Foundation, Avda Gaspar Aguilar 90, 46017, Valencia, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Rocha
authors.forename: N
authors.initials: N
authors.lastname: Apostolova
authors.forename: A
authors.initials: A
authors.lastname: Hernandez-Mijares
authors.forename: R
authors.initials: R
authors.lastname: Herance
authors.forename: V M
authors.initials: VM
authors.lastname: Victor
mesh_terms: D000975:Antioxidants / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000188:drug therapy*; D042783:Endothelial Cells / Q000378:metabolism / Q000502:physiology; D006801:Humans; D008928:Mitochondria / Q000378:metabolism* / Q000502:physiology; D018384:Oxidative Stress; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000975:Antioxidants; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species