title: Pathogenesis of target organ damage in hypertension: role of mitochondrial oxidative stress.
abstract: Hypertension causes target organ damage (TOD) that involves vasculature, heart, brain and kidneys. Complex biochemical, hormonal and hemodynamic mechanisms are involved in the pathogenesis of TOD. Common to all these processes is an increased bioavailability of reactive oxygen species (ROS). Both in vitro and in vivo studies explored the role of mitochondrial oxidative stress as a mechanism involved in the pathogenesis of TOD in hypertension, especially focusing on atherosclerosis, heart disease, renal failure, cerebrovascular disease. Both dysfunction of mitochondrial proteins, such as uncoupling protein-2 (UCP2), superoxide dismutase (SOD) 2, peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α), calcium channels, and the interaction between mitochondria and other sources of ROS, such as NADPH oxidase, play an important role in the development of endothelial dysfunction, cardiac hypertrophy, renal and cerebral damage in hypertension. Commonly used anti-hypertensive drugs have shown protective effects against mitochondrial-dependent oxidative stress. Notably, few mitochondrial proteins can be considered therapeutic targets on their own. In fact, antioxidant therapies specifically targeted at mitochondria represent promising strategies to reduce mitochondrial dysfunction and related hypertensive TOD. In the present article, we discuss the role of mitochondrial oxidative stress as a contributing factor to hypertensive TOD development. We also provide an overview of mitochondria-based treatment strategies that may reveal useful to prevent TOD and reduce its progression.
authors.affiliation: Department of Clinical and Molecular Medicine, School of Medicine and Psychology, University Sapienza of Rome, Ospedale S. Andrea, Rome 00189, Italy. rubattu.speranza@neuromed.it.
authors.forename: Speranza
authors.initials: S
authors.lastname: Rubattu
authors.affiliation: Department of Clinical and Molecular Medicine, School of Medicine and Psychology, University Sapienza of Rome, Ospedale S. Andrea, Rome 00189, Italy. beniamino.pagliaro@libero.it.
authors.forename: Beniamino
authors.initials: B
authors.lastname: Pagliaro
authors.affiliation: Department of Clinical and Molecular Medicine, School of Medicine and Psychology, University Sapienza of Rome, Ospedale S. Andrea, Rome 00189, Italy. giorgia.pierelli@alice.it.
authors.forename: Giorgia
authors.initials: G
authors.lastname: Pierelli
authors.affiliation: Department of Clinical and Molecular Medicine, School of Medicine and Psychology, University Sapienza of Rome, Ospedale S. Andrea, Rome 00189, Italy. caterina.santolamazza@gmail.com.
authors.forename: Caterina
authors.initials: C
authors.lastname: Santolamazza
authors.affiliation: Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Neuromed, Pozzilli 86077, Italy. saradicastro@yahoo.it.
authors.forename: Sara Di
authors.initials: SD
authors.lastname: Castro
authors.affiliation: Department of Clinical and Molecular Medicine, School of Medicine and Psychology, University Sapienza of Rome, Ospedale S. Andrea, Rome 00189, Italy. silvia.mennuni@gmail.com.
authors.forename: Silvia
authors.initials: S
authors.lastname: Mennuni
authors.affiliation: Department of Clinical and Molecular Medicine, School of Medicine and Psychology, University Sapienza of Rome, Ospedale S. Andrea, Rome 00189, Italy. massimo.volpe@uniroma1.it.
authors.forename: Massimo
authors.initials: M
authors.lastname: Volpe
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D001921:Brain / Q000503:physiopathology; D006321:Heart / Q000503:physiopathology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D006973:Hypertension / Q000188:drug therapy / Q000473:pathology*; D007668:Kidney / Q000503:physiopathology; D008928:Mitochondria / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000975:Antioxidants; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D017382:Reactive Oxygen Species