Limits...
Pathogenesis of target organ damage in hypertension: role of mitochondrial oxidative stress.

Rubattu S, Pagliaro B, Pierelli G, Santolamazza C, Castro SD, Mennuni S, Volpe M - Int J Mol Sci (2014)

Bottom Line: Commonly used anti-hypertensive drugs have shown protective effects against mitochondrial-dependent oxidative stress.In fact, antioxidant therapies specifically targeted at mitochondria represent promising strategies to reduce mitochondrial dysfunction and related hypertensive TOD.We also provide an overview of mitochondria-based treatment strategies that may reveal useful to prevent TOD and reduce its progression.

View Article: PubMed Central - PubMed

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.

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.

Show MeSH

Related in: MedlinePlus

Representation of main molecular pathways linking mitochondrial dysfunction with TOD development in hypertension. NAD: Nicotinamide adenine dinucleotide; NADPH ox: Nicotinamide adenine dinucleotide phosphate oxidase; GPX: Glutathione peroxidase; CuZnSOD: Copper–zinc superoxide dismutase; CytC: Cytochrome C; CoQ: Coenzyme Q; SERCA: Sarco/endoplasmic reticulum Ca2+–ATPase; MCU: Mitochondrial Ca2+ uniporter; NCX: Na+/Ca2+ exchanger; ADP: Adenosine diphosphate; ATP: Adenosine triphosphate; mtNOS: Mitochondrial nitric oxide synthase; NO: Nitric oxide; MnSOD: Manganese superoxide dismutase; ROS: Reactive oxygen species; TOD: Target organ damage; OMM: Outer mitochondrial membrane; IMS: Intermembrane space; and IMM: Inner mitochondrial membrane; I: Complex I, NADH dehydrogenase; II: Complex II, succinate dehydrogenase; III: Complex III, cytochrome bc1 complex; IV: Complex IV, cytochrome c oxidase; V: Complex V, ATP synthase.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4307277&req=5

ijms-16-00823-f001: Representation of main molecular pathways linking mitochondrial dysfunction with TOD development in hypertension. NAD: Nicotinamide adenine dinucleotide; NADPH ox: Nicotinamide adenine dinucleotide phosphate oxidase; GPX: Glutathione peroxidase; CuZnSOD: Copper–zinc superoxide dismutase; CytC: Cytochrome C; CoQ: Coenzyme Q; SERCA: Sarco/endoplasmic reticulum Ca2+–ATPase; MCU: Mitochondrial Ca2+ uniporter; NCX: Na+/Ca2+ exchanger; ADP: Adenosine diphosphate; ATP: Adenosine triphosphate; mtNOS: Mitochondrial nitric oxide synthase; NO: Nitric oxide; MnSOD: Manganese superoxide dismutase; ROS: Reactive oxygen species; TOD: Target organ damage; OMM: Outer mitochondrial membrane; IMS: Intermembrane space; and IMM: Inner mitochondrial membrane; I: Complex I, NADH dehydrogenase; II: Complex II, succinate dehydrogenase; III: Complex III, cytochrome bc1 complex; IV: Complex IV, cytochrome c oxidase; V: Complex V, ATP synthase.

Mentions: Based on the evidence discussed above, summarized in Figure 1, mitochondrial dysfunction and the consequent oxidative damage emerges as a relevant contributory factor to heart, brain, kidney and vascular damage in hypertension. It is therefore important to continue focusing on targeted mitochondria therapies in order to better understand a major mechanism underlying the pathogenesis of TOD in arterial hypertension.


Pathogenesis of target organ damage in hypertension: role of mitochondrial oxidative stress.

Rubattu S, Pagliaro B, Pierelli G, Santolamazza C, Castro SD, Mennuni S, Volpe M - Int J Mol Sci (2014)

Representation of main molecular pathways linking mitochondrial dysfunction with TOD development in hypertension. NAD: Nicotinamide adenine dinucleotide; NADPH ox: Nicotinamide adenine dinucleotide phosphate oxidase; GPX: Glutathione peroxidase; CuZnSOD: Copper–zinc superoxide dismutase; CytC: Cytochrome C; CoQ: Coenzyme Q; SERCA: Sarco/endoplasmic reticulum Ca2+–ATPase; MCU: Mitochondrial Ca2+ uniporter; NCX: Na+/Ca2+ exchanger; ADP: Adenosine diphosphate; ATP: Adenosine triphosphate; mtNOS: Mitochondrial nitric oxide synthase; NO: Nitric oxide; MnSOD: Manganese superoxide dismutase; ROS: Reactive oxygen species; TOD: Target organ damage; OMM: Outer mitochondrial membrane; IMS: Intermembrane space; and IMM: Inner mitochondrial membrane; I: Complex I, NADH dehydrogenase; II: Complex II, succinate dehydrogenase; III: Complex III, cytochrome bc1 complex; IV: Complex IV, cytochrome c oxidase; V: Complex V, ATP synthase.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4307277&req=5

ijms-16-00823-f001: Representation of main molecular pathways linking mitochondrial dysfunction with TOD development in hypertension. NAD: Nicotinamide adenine dinucleotide; NADPH ox: Nicotinamide adenine dinucleotide phosphate oxidase; GPX: Glutathione peroxidase; CuZnSOD: Copper–zinc superoxide dismutase; CytC: Cytochrome C; CoQ: Coenzyme Q; SERCA: Sarco/endoplasmic reticulum Ca2+–ATPase; MCU: Mitochondrial Ca2+ uniporter; NCX: Na+/Ca2+ exchanger; ADP: Adenosine diphosphate; ATP: Adenosine triphosphate; mtNOS: Mitochondrial nitric oxide synthase; NO: Nitric oxide; MnSOD: Manganese superoxide dismutase; ROS: Reactive oxygen species; TOD: Target organ damage; OMM: Outer mitochondrial membrane; IMS: Intermembrane space; and IMM: Inner mitochondrial membrane; I: Complex I, NADH dehydrogenase; II: Complex II, succinate dehydrogenase; III: Complex III, cytochrome bc1 complex; IV: Complex IV, cytochrome c oxidase; V: Complex V, ATP synthase.
Mentions: Based on the evidence discussed above, summarized in Figure 1, mitochondrial dysfunction and the consequent oxidative damage emerges as a relevant contributory factor to heart, brain, kidney and vascular damage in hypertension. It is therefore important to continue focusing on targeted mitochondria therapies in order to better understand a major mechanism underlying the pathogenesis of TOD in arterial hypertension.

Bottom Line: Commonly used anti-hypertensive drugs have shown protective effects against mitochondrial-dependent oxidative stress.In fact, antioxidant therapies specifically targeted at mitochondria represent promising strategies to reduce mitochondrial dysfunction and related hypertensive TOD.We also provide an overview of mitochondria-based treatment strategies that may reveal useful to prevent TOD and reduce its progression.

View Article: PubMed Central - PubMed

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.

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.

Show MeSH
Related in: MedlinePlus