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Irodova, N L; Ланкин, В. З.; Konovalova, G K; Кочетов, А. Г.; Чазова, И Е

doi:10.1023/a:1020238026534

Cited by 39 publications

(11 citation statements)

References 7 publications

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“…This is in accordance with previous studies, which have shown increased oxidative stress in IPAH patients, such as increased levels of lipid peroxidation products in plasma, 7 increased DNA oxidation, 8 and decreased levels of antioxidants, α-tocopherol and β-carotene. 9 These results suggest that patients with PAH are under a higher oxidation state, therefore therapeutic strategies to inhibit ROS actions may be beneficial.…”

Section: Discussionsupporting

confidence: 93%

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Iron chelation inhibits the development of pulmonary vascular remodeling

Wong

Preston

Hill

et al. 2012

Free Radical Biology and Medicine

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Reactive oxygen species (ROS) have been implicated in the pathogenesis of pulmonary hypertension. Since iron is an important regulator of ROS biology, the present study examined the effect of iron chelation on the development of pulmonary vascular remodeling. The administration of an iron chelator, deferoxamine, to rats prevented chronic hypoxia-induced pulmonary hypertension and pulmonary vascular remodeling. Various iron chelators inhibited growth of cultured pulmonary artery smooth muscle cells. Protein carbonylation, an important iron-dependent biological event, was promoted in association with pulmonary vascular remodeling and cell growth. A proteomic approach identified that Rho GDP-dissociation inhibitor (a negative regulator of RhoA) is carbonylated. In human plasma, the protein carbonyl content was significantly higher in patients with idiopathic pulmonary arterial hypertension than in healthy controls. These results suggest that iron plays an important role in the ROS-dependent mechanism underlying the development of pulmonary hypertension.

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Section: Discussionsupporting

confidence: 93%

“…3–6 Patients with pulmonary arterial hypertension (PAH) are under oxidative stress as indicated by increased lipid peroxidation, 7 increased DNA oxidation, 8 and decreased levels of tocopherols and carotenoids. 9 …”

Section: Introductionmentioning

confidence: 99%

Iron chelation inhibits the development of pulmonary vascular remodeling

Wong

Preston

Hill

et al. 2012

Free Radical Biology and Medicine

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“…For example, in patients with primary PH, GPx activity in the plasma is decreased, although erythrocytes had elevated GPx activity. This disparity was greatest in patients with severe cardiac insufficiency and PH (252). Further, patients with COPD and secondary PH have lower GPx activity in erythrocytes.…”

Section: Ros Scavenging Systems In the Pulmonary Vasculaturementioning

confidence: 99%

Reactive Oxygen Species in Pulmonary Vascular Remodeling

Aggarwal

Groß

Sharma

et al. 2013

Comprehensive Physiology

126

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The pathogenesis of pulmonary hypertension is a complex multifactorial process that involves the remodeling of pulmonary arteries. This remodeling process encompasses concentric medial thickening of small arterioles, neomuscularization of previously nonmuscular capillary-like vessels, and structural wall changes in larger pulmonary arteries. The pulmonary arterial muscularization is characterized by vascular smooth muscle cell (SMC) hyperplasia and hypertrophy. In addition, in uncontrolled pulmonary hypertension, the clonal expansion of apoptosis-resistant endothelial cells leads to the formation of plexiform lesions. Based upon a large number of studies in animal models, the three major stimuli that drive the vascular remodeling process are inflammation, shear stress and hypoxia. Although, the precise mechanisms by which these stimuli impair pulmonary vascular function and structure are unknown, reactive oxygen species (ROS)-mediated oxidative damage appears to play an important role. ROS are highly reactive due to their unpaired valence shell electron. Oxidative damage occurs when the production of ROS exceeds the quenching capacity of the anti-oxidant mechanisms of the cell. ROS can be produced from complexes in the cell membrane (nicotinamide adenine dinucleotide phosphate-oxidase), cellular organelles (peroxisomes and mitochondria), and in the cytoplasm (xanthine oxidase). Furthermore, low levels of tetrahydrobiopterin (BH4) and L-arginine the rate limiting co-factor and substrate for endothelial nitric oxide synthase (eNOS), can cause the uncoupling of eNOS, resulting in decreased NO production and increased ROS production. This review will focus on the ROS generation systems, scavenger antioxidants, and oxidative stress associated alterations in vascular remodeling in pulmonary hypertension.

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“…OS is commonly recognized player at the field of PAH. Signs of OS with excessive lipid peroxidation were demonstrated in PAH patients by increased levels of isoprostanes in urine [13] and malondialdehyde in plasma [32] . The other product of lipid peroxidation is hydroxynonenal (HNE).…”

Section: Introductionmentioning

confidence: 99%

Sildenafil reduces signs of oxidative stress in pulmonary arterial hypertension: Evaluation by fatty acid composition, level of hydroxynonenal and heart rate variability

et al. 2016

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Pulmonary arterial hypertension (PAH) is a rare multifactorial disease with an unfavorable prognosis. Sildenafil therapy can improve functional capacity and pulmonary hemodynamics in PAH patients. Nowadays, it is increasingly recognized that the effects of sildenafil are pleiotropic and may also involve changes of the pro-/antioxidant balance, lipid peroxidation and autonomic control. In present study we aimed to assess the effects of sildenafil on the fatty acids (FAs) status, level of hydroxynonenal (HNE) and heart rate variability (HRV) in PAH patients. Patients with PAH were characterized by an increase in HNE and changes in the FAs composition with elevation of linoleic, oleic, docosahexanoic acids in phospholipids as well as reduced HRV with sympathetic predominance. Sildenafil therapy improved exercise capacity and pulmonary hemodynamics and reduced NT-proBNP level in PAH. Antioxidant and anti-inflammatory effects of sildenafil were noted from the significant lowering of HNE level and reduction of the phopholipid derived oleic, linoleic, docosahexanoic, docosapentanoic FAs. That was also associated with some improvement of HRV on account of the activation of the neurohumoral regulatory component. Incomplete recovery of the functional metabolic disorders in PAH patients may be assumed from the persistent increase in free FAs, reduced HRV with the sympathetic predominance in the spectral structure after treatment comparing to control group. The possibilities to improve PAH treatment efficacy through mild stimulation of free radical reactions and formation of hormetic reaction in the context of improved NO signaling are discussed.

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Cited by 39 publications

References 7 publications

Iron chelation inhibits the development of pulmonary vascular remodeling

Iron chelation inhibits the development of pulmonary vascular remodeling

Reactive Oxygen Species in Pulmonary Vascular Remodeling

Sildenafil reduces signs of oxidative stress in pulmonary arterial hypertension: Evaluation by fatty acid composition, level of hydroxynonenal and heart rate variability

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