Effect of orally active prostacyclin analogue on survival of outpatients with primary pulmonary hypertension

Nagaya, Noritoshi; Uematsu, Masaaki; Okano, Yoshiaki; Satoh, Tsuyoshi; Kyotani, Shingo; Sakamaki, Fumio; Nakanishi, Norifumi; Miyatake, Kunio; Kunieda, Takeyoshi

doi:10.1016/s0735-1097(99)00312-5

Cited by 193 publications

(107 citation statements)

References 22 publications

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“…Initial trials have shown an improvement in 6MWT, functional class and survival. 47,48 In the RCT reported by Galie et al, there was significant improvement in exercise capacity at 12 weeks. 49 However, the data from Barst et al showed no difference in 6MWT distance with oral beraprost compared to placebo at 12 months follow-up, although improvement was observed at 3 and 6 months.…”

Section: Sodium Beraprostmentioning

confidence: 97%

Pulmonary hypertension—“state of the art” management in 2012

Saxena

2012

Indian Heart Journal

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A B S T R A C TPulmonary artery hypertension (PAH) is a pathological condition of small pulmonary arteries, characterised by vascular proliferation and remodelling. The pulmonary artery pressure and pulmonary vascular resistance progressively rise, leading to right heart failure and death. Pulmonary artery hypertension may be secondary to various conditions, or it may be idiopathic where no underlying cause is identifiable. Earlier, only symptomatic treatment was available for such patients which did not change the natural history of the disease. However, over the years, improvement in understanding the pathogenesis has resulted in the development of targeted approaches to the treatment of PAH. Survival advantage has also been shown with some of the pharmacologic agents. This review article discusses the current management strategy for PAH with special emphasis on an idiopathic variety, in an Indian context.

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Section: Sodium Beraprostmentioning

confidence: 97%

Pulmonary hypertension—“state of the art” management in 2012

Saxena

2012

Indian Heart Journal

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“…Defects in hIP receptor structure and function caused by such naturally occurring mutations may ultimately lead to explanations concerning the intrinsic differences observed in the pathophysiology of cardiovascular disease and responses to therapy (e.g. variable responses to iloprost in the treatment of pulmonary hypertension) (19,20). In this study, we characterize the effects of the V25M and R212H polymorphisms on hIP function.…”

Section: Fig 2 Competition Binding For Hip1d4pmt4 V25m and R212hmentioning

confidence: 98%

Impaired Receptor Binding and Activation Associated with a Human Prostacyclin Receptor Polymorphism

Stitham

Stojanović

Hwa

2002

Journal of Biological Chemistry

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The human prostacyclin receptor (hIP) is a seven transmembrane-spanning G-protein-coupled receptor that plays an important role in vascular homeostasis. Recent genetic analyses (SNP database, NCBI) have revealed the first two polymorphisms within the coding sequence, V25M and R212H. Here we present structurefunction characterizations of these polymorphisms at physiological pH (7.4) and at an acidic pH (6.8) that would be encountered during stress such as renal, respiratory, or heart failure. Through a series of competition binding and G-protein activation assays (measured by cAMP production), we determined that the V25M polymorph exhibited agonist binding and G-protein activation similar to wild-type receptor at normal pH (7.4). However, the R212H variant demonstrated a significant decrease in binding affinity at lower pH (R212H at pH 7.4, K i ‫؍‬ 2.2 ؎ 1.2 nM; pH 6.8 K i ‫؍‬ 45.6 ؎ 12.0 nM). The R212H polymorph also exhibited abnormal activation at both pH 7.4 and pH 6.8 (pH 7.4, R212H EC 50 ‫؍‬ 2.8 ؎ 0.5 nM versus wild-type hIP EC 50 ‫؍‬ 0.5 ؎ 0.1 nM; pH 6.8, R212H EC 50 ‫؍‬ 3.2 ؎ 1.6 nM versus wild-type hIP EC 50 ‫؍‬ 0.5 ؎ 0.2 nM). Polymorphisms of the human prostacyclin receptor potentially may be important predictors of disease progress during biological stressors such as acidosis in which urgent correction of bodily pH may be required to restore normal hemostasis and vasodilation. This study provides the mechanistic basis for further research into genetic risk factors and pharmacogenetics of cardiovascular disease associated with hIP.Similar to other prostanoids, prostacyclin is a derivative of the C-20 unsaturated fatty acid arachidonic acid (5,8,11,14-eicosatetraenoic acid), and its cellular action is conveyed through cell surface G-protein-coupled receptors that predominantly couple to the heterotrimeric G-protein G s stimulating the production of cAMP (1). The human prostacyclin receptor (hIP) 1 is expressed on platelets, where it mediates inhibition of platelet aggregation and on vascular smooth muscle cells, where it mediates vascular smooth muscle relaxation. Dysfunctional prostacyclin activity has been implicated in the development of a number of cardiovascular diseases including thrombosis, myocardial infarction, stroke, myocardial ischemia, atherosclerosis, and systemic and pulmonary hypertension (2). Accordingly, IP receptor knock-out mice exhibit increased thrombosis and reduced inflammatory and pain responses (3).Limited studies have begun to identify generalized regions within the IP and other prostanoid receptors that appear crucial for ligand-binding specificity and affinity. Studies using chimeric combinations of mouse prostaglandin D (mDP) and prostaglandin I (mIP) receptors have shown that protein segments within transmembrane domains VI and VII (TMVI and TMVII) are involved in distinct binding interactions with prostacyclin side chains. In addition, TMI (along with a portion of the first extracellular loop) confers broader binding functions, incorporating recognition and interaction w...

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“…Oral beraprost has been licensed in Japan for PPH after a controlled study in 58 patients showed evidence for increased survival in patients with PPH treated with beraprost, compared to conventional treatment [46]. There is, however, no sufficient data on the long-term efficacy of beraprost and there is also no information about the use of beraprost in patients with collagen vascular disease.…”

Section: Treatmentmentioning

confidence: 99%

Pulmonary hypertension in collagen vascular disease: Table 1—

Hoeper¹

2002

Eur Respir J

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Pulmonary hypertension in collagen vascular disease. M.M. Hoeper. #ERS Journals Ltd 2002. ABSTRACT: Pulmonary hypertension is a serious but often overlooked complication in collagen vascular disease. The understanding of the development of pulmonary hypertension has increased substantially during the last years.Abnormal proliferation of pulmonary vascular cells is now being regarded as a predominant process leading to pulmonary vascular obliteration. Medical therapy focuses on prostacyclin treatment, which has been shown to improve exercise capacity and haemodynamic variables in patients with several collagen vascular diseases and pulmonary arterial hypertension.Continuous intravenous prostacyclin remains the standard treatment of associated pulmonary hypertension but less invasive alternatives such as subcutaneous treprostinil, oral beraprost or aerosolized iloprost, as well as, novel substances such as endothelin receptor antagonists may be appropriate for selected patients.

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Effect of orally active prostacyclin analogue on survival of outpatients with primary pulmonary hypertension

Abstract: The oral administration of BPS may have beneficial effects on the survival of outpatients with PPH as compared with conventional therapy alone.

Cited by 193 publications

References 22 publications

Pulmonary hypertension—“state of the art” management in 2012

Pulmonary hypertension—“state of the art” management in 2012

Impaired Receptor Binding and Activation Associated with a Human Prostacyclin Receptor Polymorphism

Pulmonary hypertension in collagen vascular disease: Table 1—

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