New and Emerging Therapies for Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) is a pulmonary vasculopathy that causes right ventricular dysfunction and exercise limitation and progresses to death. New findings from translational studies have suggested alternative pathways for treatment. These avenues include sex hormones, genetic abnormalities and DNA damage, elastase inhibition, metabolic dysfunction, cellular therapies, and anti-inflammatory approaches. Both novel and repurposed compounds with rationale from preclinical experimental models and human cells are now in clinical trials in patients with PAH. Findings from these studies will elucidate the pathobiology of PAH and may result in clinically important improvements in outcome.

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Clinical Trials Targeting Metabolism in Pulmonary Arterial Hypertension

Advances in Pulmonary Hypertension ◽

10.21693/1933-088x-17.3.110 ◽

2018 ◽

Vol 17 (3) ◽

pp. 110-114 ◽

Cited By ~ 1

Author(s):

Evan L. Brittain

Keyword(s):

Clinical Trials ◽

Pulmonary Arterial Hypertension ◽

Arterial Hypertension ◽

Aerobic Glycolysis ◽

Experimental Models ◽

Pulmonary Vasculature ◽

Acid Oxidation ◽

Metabolic Dysfunction ◽

Metabolic Derangement ◽

Pulmonary Arterial

Metabolic derangement is a pathologic feature of pulmonary arterial hypertension (PAH).1 Metabolic abnormalities such as aerobic glycolysis and impaired fatty acid oxidation are consistently observed across different animal models of PAH. Importantly, altered metabolism in human PAH and experimental models is not restricted to the pulmonary vasculature, raising the possibility that PAH is a systemic metabolic disease.2 For example, lipid accumulation is present in the myocardium and skeletal muscle of humans with PAH and the right ventricle exhibits increased glucose uptake compared with matched controls. As a result of these observations, targeting metabolic dysfunction has emerged as an important therapeutic approach for patients with PAH.3 This article will review key aspects of metabolism in PAH, existing metabolic data in humans, and will describe completed and ongoing clinical trials targeting metabolic dysfunction in patients with PAH.

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Current and Emerging Therapies for Pulmonary Arterial Hypertension

Hospital Pharmacy ◽

10.1310/hpj48s4-s7 ◽

2013 ◽

Vol 48 (Supplement 4) ◽

pp. S7-S14

Author(s):

Rebekah Hanson

Keyword(s):

Pulmonary Arterial Hypertension ◽

Arterial Hypertension ◽

Emerging Therapies ◽

Pulmonary Arterial

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Pulmonary arterial hypertension: a disease of tethers, SNAREs and SNAPs?

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.01386.2006 ◽

2007 ◽

Vol 293 (1) ◽

pp. H77-H85 ◽

Cited By ~ 17

Author(s):

Pravin B. Sehgal ◽

Somshuvra Mukhopadhyay

Keyword(s):

Pulmonary Arterial Hypertension ◽

Arterial Hypertension ◽

Membrane Trafficking ◽

Experimental Models ◽

Electron Microscopic ◽

Surface Receptors ◽

Arterial Lesions ◽

Microscopic Studies ◽

Pulmonary Arterial ◽

Membrane Tethers

Histological and electron microscopic studies over the past four decades have highlighted “plump,” “enlarged” endothelial, smooth muscle, and fibroblastic cellular elements with increased endoplasmic reticulum, Golgi stacks, and vacuolation in pulmonary arterial lesions in human and in experimental (hypoxia and monocrotaline) pulmonary arterial hypertension. However, the contribution of disrupted intracellular membrane trafficking in the pathobiology of this disease has received insufficient attention. Recent studies suggest a pathogenetic role of the disruption of intracellular trafficking of vasorelevant proteins and cell-surface receptors in the development of this disease. The purpose of this essay is to highlight the molecular regulation of vesicular trafficking by membrane tethers, SNAREs and SNAPs, and to suggest how their dysfunction, directly and/or indirectly, might contribute to development of pulmonary arterial hypertension in experimental models and in humans, including that due to mutations in bone morphogenetic receptor type 2.

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Pulmonary arterial hypertension and acute and chronic thromboembolism

ESC CardioMed ◽

10.1093/med/9780198784906.003.0079 ◽

2018 ◽

pp. 406-409

Author(s):

Thomas Henzler

Keyword(s):

Computed Tomography ◽

Pulmonary Embolism ◽

Pulmonary Hypertension ◽

Pulmonary Arterial Hypertension ◽

Arterial Hypertension ◽

Imaging Modality ◽

Chronic Thromboembolic Pulmonary Hypertension ◽

Right Ventricular Dysfunction ◽

Chronic Pulmonary Embolism ◽

Pulmonary Arterial

Pulmonary arterial hypertension (PAH) and acute and chronic pulmonary embolism represent severe cardiovascular diseases with a high mortality if left undiagnosed and untreated. Computed tomography of the chest plays a pivotal role in the diagnosis of all three disorders. In acute pulmonary embolism, computed tomography pulmonary angiography has become the gold-standard imaging modality due to its high diagnostic accuracy, cost-effectiveness, 24-hour availability at most institutions, as well as the ability to diagnose alternative chest pathologies and right ventricular dysfunction within a single examination. In PAH, computed tomography of the chest is also deeply embedded within the diagnostic algorithm in order to exclude other causes of pulmonary hypertension, such as structural lung disease and chronic thromboembolic pulmonary hypertension of left heart disease. This article intends to provide a short overview on imaging techniques and characteristic findings in PAH, as well as acute and chronic pulmonary embolism.

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