Novel Therapeutic Approaches of Pulmonary Arterial Hypertension

AbstractPulmonary arterial hypertension (PAH) is an uncommon disease characterized progressive remodeling of pulmonary vasculature. Although treatment for PAH have improved in last two decades but the outcome remains fatal. Currently, the therapies for PAH target three well-established pathways the nitric oxide (NO) pathway, endothelin receptors, and prostanoids. There are multiple potential targets for development of newer drugs in PAH which requires meticulous research and clinical trials.

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Novel therapeutic approaches for pulmonary arterial hypertension: Unique molecular targets to site-specific drug delivery

Journal of Controlled Release ◽

10.1016/j.jconrel.2015.05.287 ◽

2015 ◽

Vol 211 ◽

pp. 118-133 ◽

Cited By ~ 23

Author(s):

Bhuvaneshwar Vaidya ◽

Vivek Gupta

Keyword(s):

Drug Delivery ◽

Pulmonary Arterial Hypertension ◽

Arterial Hypertension ◽

Molecular Targets ◽

Specific Drug ◽

Therapeutic Approaches ◽

Site Specific ◽

Pulmonary Arterial ◽

Novel Therapeutic

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The Nitric Oxide Pathway in Pulmonary Arterial Hypertension: Pathomechanism, Biomarkers and Drug Targets

Current Medicinal Chemistry ◽

10.2174/0929867327666200522215047 ◽

2020 ◽

Vol 27 (42) ◽

pp. 7168-7188

Author(s):

Zsófia Lázár ◽

Martina Mészáros ◽

Andras Bikov

Keyword(s):

Nitric Oxide ◽

Pulmonary Arterial Hypertension ◽

Arterial Hypertension ◽

Soluble Guanylate Cyclase ◽

Current Knowledge ◽

Muscle Tone ◽

Degradation Products ◽

Guanosine Monophosphate ◽

Pulmonary Vasculature ◽

Pulmonary Arterial

The altered Nitric Oxide (NO) pathway in the pulmonary endothelium leads to increased vascular smooth muscle tone and vascular remodelling, and thus contributes to the development and progression of pulmonary arterial hypertension (PAH). The pulmonary NO signalling is abrogated by the decreased expression and dysfunction of the endothelial NO synthase (eNOS) and the accumulation of factors blocking eNOS functionality. The NO deficiency of the pulmonary vasculature can be assessed by detecting nitric oxide in the exhaled breath or measuring the degradation products of NO (nitrite, nitrate, S-nitrosothiol) in blood or urine. These non-invasive biomarkers might show the potential to correlate with changes in pulmonary haemodynamics and predict response to therapies. Current pharmacological therapies aim to stimulate pulmonary NO signalling by suppressing the degradation of NO (phosphodiesterase- 5 inhibitors) or increasing the formation of the endothelial cyclic guanosine monophosphate, which mediates the downstream effects of the pathway (soluble guanylate cyclase sensitizers). Recent data support that nitrite compounds and dietary supplements rich in nitrate might increase pulmonary NO availability and lessen vascular resistance. This review summarizes current knowledge on the involvement of the NO pathway in the pathomechanism of PAH, explores novel and easy-to-detect biomarkers of the pulmonary NO.

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Novel therapeutic approaches in pulmonary arterial hypertension: Focus on tadalafil

Drugs of Today ◽

10.1358/dot.2011.47.2.1544337 ◽

2011 ◽

Vol 47 (2) ◽

pp. 145 ◽

Cited By ~ 15

Author(s):

Y.D. Levin ◽

R.J. White

Keyword(s):

Pulmonary Arterial Hypertension ◽

Arterial Hypertension ◽

Therapeutic Approaches ◽

Pulmonary Arterial ◽

Novel Therapeutic

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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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