Novel diagnostic and therapeutic approaches to pulmonary hypertension due to the unilateral absence of a pulmonary artery.
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ABSTRACT:
SUBMITTER: Nagamatsu Y
PROVIDER: S-EPMC8318494 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:IntroductionPulmonary arterial hypertension (PAH) is a rare disorder associated with abnormally elevated pulmonary pressures that, if untreated, leads to right heart failure and premature death. The goal of drug development for PAH is to develop effective therapies that halt, or ideally, reverse the obliterative vasculopathy that results in vessel loss and obstruction of blood flow to the lungs.Areas coveredThis review summarizes the current approach to candidate discovery in PAH and discusses the currently available drug discovery methods that should be implemented to prioritize targets and obtain a comprehensive pharmacological profile of promising compounds with well-defined mechanisms.Expert opinionTo improve the successful identification of leading drug candidates, it is necessary that traditional pre-clinical studies are combined with drug screening strategies that maximize the characterization of biological activity and identify relevant off-target effects that could hinder the clinical efficacy of the compound when tested in human subjects. A successful drug discovery strategy in PAH will require collaboration of clinician scientists with medicinal chemists and pharmacologists who can identify compounds with an adequate safety profile and biological activity against relevant disease mechanisms.
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Project description:BackgroundPulmonary artery aneurysms (PAAs) are rare and they are infrequently diagnosed due to the non-specificity of their symptoms. However, their related complications, mainly described in patients with pulmonary hypertension (PH), are associated with significant morbidity and mortality.Case summaryWe report the case of a 64-year-old woman previously operated on for pulmonary valve stenosis, who presented with rapid worsening of dyspnoea and sudden onset of chest pain. Physical examination did not show heart failure symptoms, and an echocardiogram showed significant but not severe pulmonary regurgitation with preserved right and left ventricular function. Estimated pulmonary artery (PA) pressure was normal. As myocardial ischaemia was suspected the patient underwent a coronary computed tomography angiography that showed compression of the left main coronary artery by a large PAA. Early diagnosis led to surgery that solved her symptoms.DiscussionComprehensive medical evaluation of symptomatic patients with PA dilatation, even in the absence of PH, is key to rule out the possibility of serious complications as soon as possible.
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Project description:Right heart failure results from advanced pulmonary hypertension (PH) and has a poor prognosis. There are few available treatments for right heart failure. Pulmonary artery remodeling, including changes in pulmonary artery endothelial cells to endothelial-mesenchymal cells, and aberrant fibroblast and pulmonary artery smooth muscle cell (PASMC) proliferation, are characteristics of the pathophysiological process of PH. As a result, the clinical situation requires novel PH diagnostic and treatment targets.
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