Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.2 (guanylate cyclase)
 8,497 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pulmonary hypertension (PH) secondary to left heart disease (LHD) is a largely underappreciated therapeutic target. Except for a specific focus on PH consequences in patients with advanced heart failure (HF) receiving a left ventricular assist device or candidates for heart transplant, prevention and treatment of initial subclinical forms of PH are not considered a priority in the management of this chronic disease population. Nonetheless, there is recent growing evidence supporting a clinical and prognostic role of PH in the elderly populations and in HF with preserved ejection fraction (pEF). Although the prevalence of PH in these populations still remains largely unknown, there is a large potential for effective pharmacological approaches that might impact the natural history of HFpEF by targeting earlier stages. However, pharmacological studies performed to date with traditional pulmonary vasodilators (i.e. prostanoids and endothelin receptor blockers) in cohorts with HF and left-sided PH have not been positive, primarily because of concomitant systemic hypotension and hepatic toxicity. The encouraging preliminary data with more selective well-tolerated pulmonary vasodilators, such as phosphodiesterase type 5 inhibitors and guanylate cyclase stimulators/activators, however, suggest the need for new targets of pulmonary microvascular dysfunction and for treating PH-LHD at both early and later stages of the disease process.
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PMID:Impact of pharmacologic interventions--treating endothelial dysfunction and group 2 pulmonary hypertension. 2544 53

Pulmonary hypertension (PH) secondary to left heart disease, classified as Group 2, is a widely underestimated target of therapy. Prevention and treatment of initial subclinical stages are not valued as a priority in the management of this chronic disease population, whereas attention is high for PH consequences in patients with advanced heart failure (HF) requiring a left ventricular mechanical assist device or heart transplant candidates. Even so, there is a growing interest toward the evidence of a clinical and prognostic role of PH in the elderly populations and in HF with preserved ejection fraction (HFpEF). Certainly, along with a prevalence definition not yet defined, the search for effective pharmacological approaches that might favorably affect the aging process and the natural history of HFpEF from earlier stages is not an easy task. Pharmacological studies that have tested some traditional pulmonary arterial hypertension approved drugs (i.e., prostanoids and endothelin-1 receptor blockers) primarily in PH and HF with reduced ejection fraction have not been positive, especially because of concomitant side effects, i.e., systemic hypotension, fluid retention and hepatic toxicity. In recent years, interest has moved toward drugs overexpressing the nitric oxide (NO)-cyclic guanosine monophosphate pathway with recent availability of well-tolerated selective pulmonary vasodilators, such as phosphodiesterase type 5 inhibitors and guanylate cyclase stimulators. Single center studies performed with these drugs have shown good tolerability and safety profile providing alternating hemodynamic results mainly because of recruitment of patients at different stages of the pulmonary vascular disease. Nonetheless, the overexpression of NO pathway appears to remain the most solid background for targeting lung microvessel dysfunction and treating RV dysfunction since the earliest stages of the disease.
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PMID:Group 2 PH: Medical Therapy. 2738 9

Pulmonary arterial hypertension (PAH) is a chronic disease that results in narrowing of the small pre-capillary pulmonary arteries leading to elevation of pulmonary artery pressure and pulmonary vascular resistance, subsequent right ventricular failure, and if unchecked, death. Advances in the treatment of PAH over the last two decades have markedly improved survival. These improvements reflect a combination of changes in treatments, improved patient care strategies, and varying disease phenotypes in the PAH population. Currently approved therapies for PAH are directed at the recognized abnormalities within the pulmonary vasculature and include endothelin receptor antagonists, phosphodiesterase-5 inhibitors, soluble guanylate cyclase stimulators, and prostacyclin pathway agents. Most of these drugs have been approved on the basis of short-term trials that mainly demonstrated improvements in exercise capacity. More recently, long-term, event-driven trials of novel drugs have been performed, demonstrating new efficacy parameters. There have also been exciting advances in the understanding of right heart failure pathophysiology in PAH that have the potential to inspire the development of right ventricular targeted therapy and continued discoveries in the heterogeneity of disease and response to treatment has great potential for developing more 'personalized' therapeutic options. In this article, we review the current available data regarding the management of PAH, with an emphasis on the pharmacologic therapies and discussion of novel therapeutic directions for the treatment of this fatal disease.
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PMID:Steps forward in the treatment of pulmonary arterial hypertension: latest developments and clinical opportunities. 2834 27