Comparative Effectiveness of Oral Medications for Pulmonary Arterial Hypertension

Igarashi, Ataru; Inoue, Sachie; Ishii, Tomonori; Tsutani, Kiichiro; Watanabe, Hiroshi

doi:10.1536/ihj.15-459

Cited by 19 publications

(33 citation statements)

References 27 publications

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“…33,34) However, the RV is the major determinant of functional state and prognosis in PAH. 35) Thus, PPARγ's advantage lies in offering the possibility of therapies that treat the RV and pulmonary artery as a whole.…”

Section: Discussionmentioning

confidence: 99%

PPARγ Alleviates Right Ventricular Failure Secondary to Pulmonary Arterial Hypertension in Rats

Xü

Liu

et al. 2017

Int. Heart J.

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SummaryPulmonary arterial hypertension (PAH) is characterized by pulmonary vascular remodeling leading to right ventricular hypertrophy (RVH) and failure. Peroxisome proliferator-activated receptor γ (PPARγ), a member of nuclear receptors, has been proved to ameliorate PAH. However, its effect on PAH-induced right ventricular failure (RVF) remains unknown. Therefore, we investigated the therapeutic potential of PPARγ in preventing monocrotaline (MCT)-induced RV dysfunction. The PAH model was induced by MCT administration. Male rats were administered with MCT to develop PAH and RVF formed by approximately day 30. Significant increase in RV area, RVAW resulted in an ascending RV index. However, the LV function including EF, FS, and LVID did not change significantly. PPARγ agonist prevented PAH-induced RVF by preserving RV index and preventing RVH. PPARγ's beneficial effects seem to result from various factors, including anti-apoptosis, preservation RV index, reversal of inflammation, improvement of glucolipid metabolism, reduction of ROS. In a word, PPARγ agonist prevents the development of RVF.( Int Heart J 2017; 58: 948-956)

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Section: Discussionmentioning

confidence: 99%

PPARγ Alleviates Right Ventricular Failure Secondary to Pulmonary Arterial Hypertension in Rats

Xü

Liu

et al. 2017

Int. Heart J.

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“…They are currently being used in the Measurement of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) analysis was performed in C2C12 myotubes after 2, 6, or 24 h (T0-T24) of tadalafil (1 μM) treatments. Data presented are the mean ± SD of three experiments *p < 0.05 vs CTRL; #p < 0.01 vs CTRL; §p < 0.001 vs CTRL a U/mg protein treatment of pulmonary hypertension (Igarashi et al 2016) and Raynaud's phenomenon (Kamata and Minota 2014). Furthermore, some studies have also reported the protective role of tadalafil in reducing oxidative stress in diabetic animal models (Koka et al 2013;Koka et al 2014;Chen et al 2012;Mostafa et al 2012).…”

Section: Discussionmentioning

confidence: 99%

Influence of the PDE5 inhibitor tadalafil on redox status and antioxidant defense system in C2C12 skeletal muscle cells

Duranti

Ceci

Sgrò

et al. 2017

Cell Stress and Chaperones

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Phosphodiesterase type 5 inhibitors (PDE5Is), widely known for their beneficial effects onto male erectile dysfunction, seem to exert favorable effects onto metabolism as well. Tadalafil exposure increases oxidative metabolism of C2C12 skeletal muscle cells. A rise in fatty acid (FA) metabolism, requiring more oxygen, could induce a larger reactive oxygen species (ROS) release as a byproduct thus leading to a redox imbalance. The aim of this study was to determine how PDE5I tadalafil influences redox status in skeletal muscle cells to match the increasing oxidative metabolism. To this purpose, differentiated C2C12 skeletal muscle cells were treated with tadalafil and analyzed for total antioxidant capacity (TAC) and glutathione levels as marker of redox status; enzyme activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) engaged in antioxidant defense; and lipid peroxidation (TBARS) and protein carbonyls (PrCar) as markers of oxidative damage. Tadalafil increased total intracellular glutathione (tGSH), CAT, SOD, and GPx enzymatic activities while no changes were found in TAC. A perturbation of redox status, as showed by the decrease in the ratio between reduced/oxidized glutathione (GSH/GSSG), was observed. Nevertheless, it did not cause any change in TBARS and PrCar levels probably due to the enhancement in the antioxidant enzymatic network. Taken together, these data indicate that tadalafil, besides improving oxidative metabolism, may be beneficial to skeletal muscle cells by enhancing the enzymatic antioxidant system capacity.

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“…Sildenafil inhibits cGMP‐specific PDE5, an enzyme that promotes degradation of cGMP. Inhibition of PDE5 results in smooth muscle relaxation, which alleviates erectile dysfunction and pulmonary arterial hypertension (Balhara et al, ; Igarashi et al ., ). Sildenafil therapy increased HDL‐C and decreased P‐selectin and LDL‐C levels through mechanisms which are not yet understood (Mandosi et al ., ).…”

Section: Pharmaceutical Approachesmentioning

confidence: 99%

Current and future therapies for addressing the effects of inflammation on HDL cholesterol metabolism

Iqbal

Baker

Khan

et al. 2017

British J Pharmacology

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Cardiovascular disease (CVD) is a major cause of morbidity and mortality worldwide. Inflammatory processes arising from metabolic abnormalities are known to precipitate the development of CVD. Several metabolic and inflammatory markers have been proposed for predicting the progression of CVD, including high density lipoprotein cholesterol (HDL-C). For~50 years, HDL-C has been considered as the atheroprotective 'good' cholesterol because of its strong inverse association with the progression of CVD. Thus, interventions to increase the concentration of HDL-C have been successfully tested in animals; however, clinical trials were unable to confirm the cardiovascular benefits of pharmaceutical interventions aimed at increasing HDL-C levels. Based on these data, the significance of HDL-C in the prevention of CVD has been called into question. Fundamental in vitro and animal studies suggest that HDL-C functionality, rather than HDL-C concentration, is important for the CVD-preventive qualities of HDL-C. Our current review of the literature positively demonstrates the negative impact of systemic and tissue (i.e. adipose tissue) inflammation in the healthy metabolism and function of HDL-C. Our survey indicates that HDL-C may be a good marker of adipose tissue health, independently of its atheroprotective associations. We summarize the current findings on the use of antiinflammatory drugs to either prevent HDL-C clearance or improve the function and production of HDL-C particles. It is evident that the therapeutic agents currently available may not provide the optimal strategy for altering HDL-C metabolism and function, and thus, further research is required to supplement this mechanistic approach for preventing the progression of CVD. LINKED ARTICLES IntroductionThere have been several sharp turns in the evidence trail marking the atheroprotective role of high density lipoproteins (HDLs). Very early studies on dyslipidaemia highlighted the positive correlation between total triglycerides (TGs) with the risk of developing cardiovascular disease (CVD). Since the mid-1970s, numerous epidemiological and animal studies, including the Framingham Study (Gordon et al., 1977), reported that HDL cholesterol (HDL-C) has the strongest inverse relationship with the development of CVD of the known serum lipid factors (Badimon et al., 1990;Rubin et al., 1991;Liu et al., 1994;Plump et al., 1994). This association is underpinned by reverse cholesterol transport (RCT) -a process by which HDL-C transfers the cholesterol from peripheral cells, for example, lipid-laden foam cells, to the liver for secretion into bile and faeces. The promotion of RCT is considered a major anti-atherogenic function of HDL-C (Gofman et al., 1966;Miller and Miller, 1975;Rhoads et al., 1976). Based on these findings, interventions to increase the levels of HDL-C were developed but found to be ineffective for preventing cardiovascular outcomes in several large clinical trials (Brousseau et al., 2004;McKenney et al., 2006;Barter et al., 2007;Boden et al., 2011;Lü...

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Comparative Effectiveness of Oral Medications for Pulmonary Arterial Hypertension

Cited by 19 publications

References 27 publications

PPARγ Alleviates Right Ventricular Failure Secondary to Pulmonary Arterial Hypertension in Rats

PPARγ Alleviates Right Ventricular Failure Secondary to Pulmonary Arterial Hypertension in Rats

Influence of the PDE5 inhibitor tadalafil on redox status and antioxidant defense system in C2C12 skeletal muscle cells

Current and future therapies for addressing the effects of inflammation on HDL cholesterol metabolism

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