scholarly journals Chronic and moderate consumption of reduced-alcohol wine confers cardiac benefits in a rat model of pulmonary arterial hypertension

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Patrick Diaba-Nuhoho ◽  
Martin Cour ◽  
Nkanyiso Hadebe ◽  
David Marais ◽  
Sandrine Lecour ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Rat Model ◽  
Red Wine ◽  
Thiobarbituric Acid ◽  
Conjugated Dienes ◽  
Thiobarbituric Acid Reactive Substances ◽  
Acceleration Time ◽  
Pulmonary Arterial

Abstract Objectives In pulmonary arterial hypertension (PAH), right ventricular (RV) dysfunction develops via mechanisms involving oxidative stress. Moderate and chronic red wine (RW) consumption reduces oxidative stress and confers cardioprotection but its effect on PAH is unknown. We evaluated whether moderate and chronic consumption of reduced-alcohol RW (RARW) confers cardioprotection in a monocrotaline (MCT)-induced PAH rat model. Results Rats were randomly grouped: control; MCT; RARW; MCT + RARW. Wine was diluted to mimic moderate intake for humans, and consumed from 7 days before, until 28 days after MCT-injection. Echocardiography measured pulmonary artery acceleration time (PAAT) and RV thickness. Conjugated dienes (CD), and thiobarbituric acid reactive substances (TBARS) concentrations were assessed. MCT induced RV thickness and decreased PAAT compared to controls [1.22 ± 0.09 mm vs 0.46 ± 0.02 mm and 14 ± 1 vs 23 ± 2 m/s, respectively (p < 0.001)]. Chronic RARW consumption limited MCT-induced RV hypertrophy and increased PAAT. CD and TBARS increased in MCT-treated animals compared to controls (672 ± 43 nmol/L vs 453 ± 35 nmol/L; p < 0.01 and 13 ± 2 µmol/L vs 4 ± 0.3 µmol/L; p < 0.01). RARW reduced MCT-induced CD (472 ± 27 nmol/L vs 672 ± 43 nmol/L; p < 0.01). Conclusion Chronic and moderate intake of RARW ameliorates MCT-induced PAH in rats, which may be partly attributable to reduction of lipid peroxidation.

scholarly journals Effects of inorganic nitrate in a rat model of monocrotaline‐induced pulmonary arterial hypertension

2019 ◽  
Vol 126 (2) ◽  
pp. 99-109
Author(s):  
Eva Malikova ◽  
Mattias Carlström ◽  
Zuzana Kmecova ◽  
Margareta Marusakova ◽  
Bianka Zsigmondova ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Rat Model ◽  
Inorganic Nitrate ◽  
Pulmonary Arterial

Safflower injection inhibits pulmonary arterial remodeling in a monocrotaline-induced pulmonary arterial hypertension rat model

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Aifeng Chen ◽  
Shibiao Ding ◽  
Liangliang Kong ◽  
Jianpu Xu ◽  
Fei He ◽  
...  
Keyword(s):  
Growth Factor ◽  
Pulmonary Arterial Hypertension ◽  
Pulmonary Artery ◽  
Arterial Hypertension ◽  
Cardiac Muscle ◽  
Rat Model ◽  
Dependent Manner ◽  
Arterial Remodeling ◽  
Pulmonary Arterial ◽  
Dose Dependent

AbstractPulmonary arterial hypertension (PAH) is a group of diseases with an increase of pulmonary artery pressure (PAP) and pulmonary vascular resistance. Here, the effects of safflower injection, a preparation of Chinese herbs, was investigated in a monocrotaline (MCT)-induced PAH rat model. PAP, carotid artery pressure (CAP), and the right ventricular hypertrophy index (RVHI) increased in the PAH group, while safflower injection was able to inhibit this increase to similar levels as observed in the normal group. The arteriole wall of the lungs and cardiac muscle were thickened and edema was observed in the PAH group, while these pathologies were improved in the herb-treated group in a dose-dependent manner. MCT treatment induced proliferation of pulmonary artery smooth muscle cells (PASMCs), which was inhibited by safflower injection in a dose-dependent manner. Our experimental results demonstrated that safflower injection can regulate pulmonary arterial remodeling through affecting the expression of connective tissue growth factor, transforming growth factor-β, integrin, collagen or fibronectin, which subsequently affected the thicknesses of the arteriole walls of the lungs and cardiac muscle, and thereby benefits the control of PAH. This means safflower injection improved the abnormalities in PAP, CAP and RVHI, and pulmonary arterial remodeling through regulation of remodeling factors.

scholarly journals Effects of ovariectomy on antioxidant defence systems in the right ventricle of female rats with pulmonary arterial hypertension induced by monocrotaline

2018 ◽  
Vol 96 (3) ◽  
pp. 295-303 ◽  
Author(s):  
Rafaela Siqueira ◽  
Rafael Colombo ◽  
Adriana Conzatti ◽  
Alexandre Luz de Castro ◽  
Cristina Campos Carraro ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Pulmonary Arterial Hypertension ◽  
Right Ventricle ◽  
Protein Expression ◽  
Arterial Hypertension ◽  
Female Rats ◽  
Antioxidant Defenses ◽  
Thioredoxin 1 ◽  
Pulmonary Arterial ◽  
The Right

The aim of this study was to evaluate the impact of ovariectomy on oxidative stress in the right ventricle (RV) of female rats with pulmonary arterial hypertension (PAH) induced by monocrotaline (MCT). Rats were divided into 4 groups (n = 6 per group): sham (S), sham + MCT (SM), ovariectomized (O), and ovariectomized + MCT (OM). MCT (60 mg·kg−1 i.p.) was injected 1 week after ovariectomy or sham surgery. Three weeks later, echocardiographic analysis and RV catheterisation were performed. RV morphometric, biochemical, and protein expression analysis through Western blotting were done. MCT promoted a slight increase in pulmonary artery pressure, without differences between the SM and OM groups, but did not induce RV hypertrophy. RV hydrogen peroxide increased in the MCT groups, but SOD, CAT, and GPx activities were also enhanced. Non-classical antioxidant defenses diminished in ovariectomized groups, probably due to a decrease in the nuclear factor Nrf2. Hemoxygenase-1 and thioredoxin-1 protein expression was increased in the OM group compared with SM, being accompanied by an elevation in the estrogen receptor β (ER-β). Hemoxygenase-1 and thioredoxin-1 may be involved in the modulation of oxidative stress in the OM group, and this could be responsible for attenuation of PAH and RV remodeling.

Abstract 382: Cyclophilin A (CypA) is a Pathogenic Mediator of Pulmonary Arterial Hypertension

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Chao Xue
Keyword(s):  
Oxidative Stress ◽  
Smooth Muscle ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Specific Inhibitor ◽  
Cyclophilin A ◽  
Pulmonary Vasculature ◽  
Tunel Staining ◽  
Mesenchymal Transition ◽  
Pulmonary Arterial

Rationale: Pulmonary arterial hypertension (PAH) is a devastating disease in which oxidative stress has been proposed to mediate pathological changes to the pulmonary vasculature such as endothelial cell (EC) apoptosis, endothelial to mesenchymal transition (EndMT), vascular smooth muscle cell (VSMC) proliferation, and inflammation. Our previous study showed that cyclophilin A (CypA) was secreted from EC and VSMC in response to oxidative stress, and much of the secreted CypA was acetylated (AcK-CypA). Furthermore, CypA was increased in the plasma of patients with PAH. Objective: To evaluate the cell- s pecific role of CypA in PAH and compare the relative effects of AcK-CypA and CypA on EC apoptosis, development of an inflammatory EC phenotype and EndMT. Methods and Results: Transgenic overexpression of CypA in EC, but not SMC, caused a PAH phenotype including increased pulmonary artery pressure, α-smooth muscle actin expression in small arteries, and CD45 positive cells in the lungs. Mechanistic analysis using cultured mouse lung microvascular EC showed that CypA and AcK-CypA increased apoptosis measured by caspase 3 cleavage and TUNEL staining. MM284, a specific inhibitor of extracellular CypA, prevented EC apoptosis. In addition, CypA and AcK-CypA promoted an EC inflammatory phenotype assessed by increased VCAM1 and ICAM1 expression, phosphorylation of p65, and degradation of IkB. Furthermore, CypA and AcK-CypA promoted EndMT assayed by change in cell morphology, increased mesenchymal markers and EndMT related transcription factors. At all concentrations, AcK-CypA stimulated greater increases in apoptosis, inflammation and EndMT than CypA. Conclusions: EC-derived CypA (especially AcK-CypA) causes PAH by a presumptive mechanism involving increased EC apoptosis, inflammation and EndMT. Our results suggest that inhibiting extracellular secreted CypA is a novel therapeutic approach for PAH.

Abstract 263: Differential Effects of 17ß-Estradiol and 16a-Hydroxyestrone in Oxidative Stress and Proliferative Responses in Human Pulmonary Artery Smooth Muscle Cells - Implications in Pulmonary Arterial Hypertension

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Katie Y Hood ◽  
Augusto C Montezano ◽  
Margaret R MacLean ◽  
Rhian M Touyz
Keyword(s):  
Oxidative Stress ◽  
Pulmonary Arterial Hypertension ◽  
Cell Growth ◽  
Arterial Hypertension ◽  
Molecular Mechanisms ◽  
Antioxidant Systems ◽  
Ros Generation ◽  
Ros Production ◽  
Differential Effects ◽  
Pulmonary Arterial

Women develop pulmonary arterial hypertension (PAH) more frequently than men. This may relate, in part, to metabolism of 17β-estradiol (E2), leading to formation of the deleterious metabolite, 16α-hydroxyestrone (16α OHE1), which plays a role in the remodelling of pulmonary arteries. Molecular mechanisms whereby 16αOHE1 influences PASMC remodelling are unclear but ROS may be important, since oxidative stress has been implicated in the pathogenesis of PAH. We hypothesised that E2 and 16αOHE1 leads to Nox-induced ROS production, which promotes PASMC damage. Cultured PASMCs were stimulated with either E2 (1nM) or 16αOHE1 (1nM) in the presence/absence of EHT1864 (100μM, Rac1 inhibitor) or tempol (antioxidant; 10μM). ROS production was assessed by chemiluminescence (O2-) and Amplex Red (H2O2). Antioxidants (thioredoxin, peroxiredoxin 1 and NQ01), regulators of Nrf2 (BACH1, Nrf2) and, marker of cell growth (PCNA) were determined by immunoblotting. E2 increased O2- production at 4h (219 ± 30% vs vehicle; p<0.05), an effect blocked by EHT1864 and tempol. E2 also increased H2O2 generation (152 ± 4%; p<0.05). Thioredoxin, NQ01 and peroxiredoxin1 (71 ± 6%; 78 ± 9%; 69 ± 8%; p<0.05 respectively) levels were decreased by E2 as was PCNA expression (72 ± 2%; p<0.05). 16αOHE1 exhibited a rapid (5 min) and exaggerated increase in ROS production (355 ± 41%; p<0.05), blocked by tempol and EHT1864. This was associated with an increase in Nox4 expression (139 ± 11% vs vehicle, p<0.05). 16αOHE1 increased BACH1, (129 ± 3%; p<0.05), a competitor of Nrf2, which was decreased (92 ± 2%). In contrast, thioredoxin expression was increased by 16aOHE1 (154 ± 22%; p<0.05). PCNA (150 ± 5%) expression was also increased after exposure to 16αOHE1. In conclusion, E2 and 16αOHE1 have differential effects on redox processes associated with PASMC growth. Whereas E2 stimulates ROS production in a slow and sustained manner without effect on cell growth, 16αOHE1 upregulates Nox4 with associated rapid increase in ROS generation and downregulation of antioxidant systems, affecting proliferation. Our findings suggest that E2 -derived metabolites may promote a pro-proliferative PASMC phenotype through Nox4-derived ROS generation. These deleterious effects may impact on vascular remodeling in PAH.

scholarly journals Changes in heart morphometric parameters over the course of a monocrotaline-induced pulmonary arterial hypertension rat model

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Mateusz K. Hołda ◽  
Elżbieta Szczepanek ◽  
Joanna Bielawska ◽  
Natalia Palka ◽  
Dorota Wojtysiak ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Rat Model ◽  
Morphometric Parameters ◽  
Pulmonary Arterial
Sign in / Sign up

Export Citation Format

Share Document