Functional adaptation and remodeling of pulmonary artery in flow-induced pulmonary hypertension

Lam, Chen Fuh; Peterson, Timothy E.; Croatt, Anthony J.; Nath, Karl A.; Katušić, Zvonimir S.

doi:10.1152/ajpheart.00375.2005

Cited by 42 publications

(33 citation statements)

References 52 publications

(57 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…COX-2 protein levels are increased in lungs from rats with PAH induced by hypoxia (Chida and Voelkel, 1996) or high pulmonary blood flow (Sato et al, 2000;Lam et al, 2005) and in hypoxic human PA smooth muscle cells (Yang et al, 2002). In addition, elevated TXA 2 levels have been demonstrated in several forms of PAH (Christman et al, 1992).…”

Section: Discussionmentioning

confidence: 99%

Type 1 Diabetes-Induced Hyper-Responsiveness to 5-Hydroxytryptamine in Rat Pulmonary Arteries via Oxidative Stress and Induction of Cyclooxygenase-2

López‐López¹,

Moral-Sanz²,

Frazziano³

et al. 2011

J Pharmacol Exp Ther

View full text Add to dashboard Cite

Recent epidemiological data suggest that diabetes is a risk factor for pulmonary arterial hypertension. The aim of the present study was to analyze the link between type 1 diabetes and pulmonary arterial dysfunction in rats. Male Sprague-Dawley rats were randomly divided into a control group (saline) and a diabetic group (70 mg/kg streptozotocin). After 6 weeks, diabetic animals showed a down-regulation of the lung bone morphogenetic protein receptor type 2, up-regulation of 5-hydroxytryptamine (5-HT) 2A receptors and cyclooxygenase-2 (COX-2) proteins as measured by Western blot analysis, and increased contractile responses to 5-HT in isolated intrapulmonary arteries. The hyper-responsiveness to 5-HT was endothelium-independent and unaffected by inhibition of nitric-oxide synthase but prevented by indomethacin, the selective COX-2 inhibitor N-[2-(cyclohexyloxyl)-4-nitrophenyl]-methane sulfonamide (NS-398), superoxide dismutase, and the NADPH oxidase inhibitor apocynin or chronic treatment with insulin. However, diabetic rats at 6 weeks did not develop elevated right ventricular pressure or pulmonary artery muscularization, whereas a longer exposure (4 months) to diabetes induced a modest, but significant, increase in right ventricular systolic pressure. In conclusion, type 1 diabetes mellitus in rats induces a number of changes in lung protein expression and pulmonary vascular reactivity characteristic of clinical and experimental pulmonary arterial hypertension but insufficient to elevate pulmonary pressure. Our results further strengthen the link between diabetes and pulmonary arterial hypertension.

show abstract

Section: Discussionmentioning

confidence: 99%

Type 1 Diabetes-Induced Hyper-Responsiveness to 5-Hydroxytryptamine in Rat Pulmonary Arteries via Oxidative Stress and Induction of Cyclooxygenase-2

López‐López¹,

Moral-Sanz²,

Frazziano³

et al. 2011

J Pharmacol Exp Ther

View full text Add to dashboard Cite

show abstract

“…Whole-lung expression of hypoxia-inducible mitogenic factor (HIMF), fibronectin, and eNOS, proteins associated with the development of PAH in some models (16)(17)(18)(19)(20), was increased by hypoxia and by 3 weeks of NAC treatment (10 mg/ml; n = 3-6 each; P < 0.05 [HIMF and fibronectin] and P < 0.01 [eNOS]; Figure 2, A-D). Of note, VEGF-A and endothelin 1 protein expression did not increase significantly with hypoxia or NAC in our model ( Figure 2, E and F).…”

Section: Nac and Snoac Cause Hypoxia-mimetic Pahmentioning

confidence: 99%

S-Nitrosothiols signal hypoxia-mimetic vascular pathology

Palmer¹,

Doctor²,

Chhabra³

et al. 2007

J. Clin. Invest.

148

159

View full text Add to dashboard Cite

NO transfer reactions between protein and peptide cysteines have been proposed to represent regulated signaling processes. We used the pharmaceutical antioxidant N-acetylcysteine (NAC) as a bait reactant to measure NO transfer reactions in blood and to study the vascular effects of these reactions in vivo. NAC was converted to S-nitroso-N-acetylcysteine (SNOAC), decreasing erythrocytic S-nitrosothiol content, both during wholeblood deoxygenation ex vivo and during a 3-week protocol in which mice received high-dose NAC in vivo. Strikingly, the NAC-treated mice developed pulmonary arterial hypertension (PAH) that mimicked the effects of chronic hypoxia. Moreover, systemic SNOAC administration recapitulated effects of both NAC and hypoxia. eNOS-deficient mice were protected from the effects of NAC but not SNOAC, suggesting that conversion of NAC to SNOAC was necessary for the development of PAH. These data reveal an unanticipated adverse effect of chronic NAC administration and introduce a new animal model of PAH. Moreover, evidence that conversion of NAC to SNOAC during blood deoxygenation is necessary for the development of PAH in this model challenges conventional views of oxygen sensing and of NO signaling.Introduction NO transfer reactions between protein and peptide cysteines have been proposed to represent regulated signaling processes (1, 2). For example, NO transfer from deoxygenated erythrocytes to glutathione ex vivo forms S-nitrosoglutathione (GSNO) (3). GSNO can signal acute vascular and central ventilatory effects characteristic of oxyhemoglobin desaturation (3-4) that are regulated by γ-glutamyl transpeptidase (GGT), GSNO reductase (GSNOR), and other enzymes (1, 3-6). However, direct measurement of S-nitrosothiol signaling in vivo has proven challenging because of the metabolism and tissue-specific localization of endogenous S-nitrosothiol species (1, 3, 4, 6). We have addressed these challenges by using N-acetylcysteine (NAC) as a bait reactant, allowing the stable NO transfer product, S-nitroso-N-acetylcysteine (SNOAC), to be distinguished by mass spectrometry (MS) from endogenous S-nitrosothiols. We report that NAC is converted to SNOAC in mice in vivo. Furthermore, chronic, systemic administration of either NAC or SNOAC to mice causes hypoxia-mimetic pulmonary arterial hypertension (PAH). These data reveal a previously unappreciated vascular toxicity of NAC and of S-nitrosothiols. Moreover, they suggest that S-nitrosothiol transfer reactions can signal hypoxia in vivo.PAH is characterized by increased pressure in the pulmonary arteries (PAs), increased RV weight, and thickening and remodeling of small PAs. Untreated human PAH can progress to right

show abstract

“…However, we did not find any significant differences in serum VEGF levels between the groups (Tables 4 and 5). Pulmonary artery pressure increases with the effect of increased pulmonary blood flow in CHD with shunt lesions (10). Eventually, pulmonary vascular resistance increases due to structural changes in the vascular bed.…”

Section: Discussionmentioning

confidence: 99%

Vasoactive mediators in congenital heart diseases with shunt lesions and pulmonary hypertension

Tunaoğlu¹,

Turan²,

Olguntürk³

et al. 2013

Turk J Med Sci

View full text Add to dashboard Cite

The aim of this study was to use a support vector machine (SVM) for the first time as a predictive method for differentiating species of Salix wood through the biometric analysis of their anatomy using wood taken from basal disks of 3 species. The purpose of a SVM is to construct optimal decision boundaries among classes in a decision plane. A decision plane separates a set of objects having different class memberships. In this study, the decision plane has 3 different wood species. Timely and accurate identification of tree species can be crucial in forestry. The similarity of structures in wood anatomy across many species, especially in the case of Salix species, means that they cannot be differentiated anatomically using traditional methods. SVM can be an effective tool for identifying similar taxa with a high percentage of accuracy. A SVM was used to differentiate Salix alba, Salix caprea, and Salix elaeagnos growing in Turkey. These Salix species are sufficiently similar that it is not possible to differentiate between them using traditional anatomical methods. However, a SVM was able to differentiate between the 3 species with a high degree of probability using the biometrics of wood anatomy. For the purposes of classification, a SVM with linear kernel function was designed; it attained an 80.6% success rate in the training group and a 95.2% success rate in the testing group. After feature selection, our SVM was able to classify the 3 species with notable success. If the number of samples were increased, the SVM would return more precise classification results.

show abstract

Functional adaptation and remodeling of pulmonary artery in flow-induced pulmonary hypertension

Cited by 42 publications

References 52 publications

Type 1 Diabetes-Induced Hyper-Responsiveness to 5-Hydroxytryptamine in Rat Pulmonary Arteries via Oxidative Stress and Induction of Cyclooxygenase-2

Type 1 Diabetes-Induced Hyper-Responsiveness to 5-Hydroxytryptamine in Rat Pulmonary Arteries via Oxidative Stress and Induction of Cyclooxygenase-2

S-Nitrosothiols signal hypoxia-mimetic vascular pathology

Vasoactive mediators in congenital heart diseases with shunt lesions and pulmonary hypertension

Contact Info

Product

Resources

About