New Drugs, Therapeutic Strategies, and Future Direction for the Treatment of Pulmonary Arterial Hypertension

2019 ◽  
Vol 26 (16) ◽  
pp. 2844-2864 ◽  
Author(s):  
Valentina Mercurio ◽  
Anna Bianco ◽  
Giacomo Campi ◽  
Alessandra Cuomo ◽  
Nermin Diab ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Therapeutic Strategies ◽  
Mechanisms Of Action ◽  
New Drugs ◽  
Therapeutic Approaches ◽  
Investigational Drugs ◽  
Pulmonary Arterial ◽  
Future Direction ◽  
Approved Drugs

Despite recent advances in Pulmonary Arterial Hypertension (PAH) treatment, this condition is still characterized by an extremely poor prognosis. In this review, we discuss the use of newly-approved drugs for PAH treatment with already known mechanisms of action (macitentan), innovative targets (riociguat and selexipag), and novel therapeutic approaches with initial up-front combination therapy. Secondly, we describe new potential signaling pathways and investigational drugs with promising role in the treatment of PAH.

scholarly journals Recent advances in the management of pulmonary arterial hypertension

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 2755 ◽  
Author(s):  
Halley Tsai ◽  
Yon K. Sung ◽  
Vinicio de Jesus Perez
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Combination Therapy ◽  
Arterial Hypertension ◽  
Soluble Guanylate Cyclase ◽  
Right Heart Failure ◽  
New Drugs ◽  
Triple Combination Therapy ◽  
Treatment Naïve ◽  
Treatment Paradigm ◽  
Pulmonary Arterial

Over the past 20 years, there has been an explosion in the development of therapeutics to treat pulmonary arterial hypertension (PAH), a rare but life-threatening disorder associated with progressive elevation of pulmonary pressures and severe right heart failure. Recently, the field has seen the introduction of riociguat, a soluble guanylate cyclase stimulator, a new endothelin receptor antagonist (macitentan), and oral prostanoids (treprostinil and selexipag). Besides new drugs, there have been significant advances in defining the role of upfront combination therapy in treatment-naïve patients as well as proposed methods to deliver systemic prostanoids by use of implantable pumps. In this review, we will touch upon the most important developments in PAH therapeutics over the last three years and how these have changed the guidelines for the treatment of PAH. These exciting developments herald a new era in the treatment of PAH which will be punctuated by the use of more clinically relevant endpoints in clinical research trials and a novel treatment paradigm that may involve upfront double- or triple-combination therapy. We anticipate that the future will make use of these strategies to test the efficacy of upcoming new drugs that aspire to reduce disease progression and improve survival in patients afflicted with this devastating disease.

scholarly journals Novel Therapeutic Approaches of Pulmonary Arterial Hypertension

2019 ◽  
Vol 28 (02) ◽  
pp. 112-117
Author(s):  
Sanjay Tyagi ◽  
Vishal Batra
Keyword(s):  
Nitric Oxide ◽  
Clinical Trials ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Endothelin Receptors ◽  
Pulmonary Vasculature ◽  
Therapeutic Approaches ◽  
Uncommon Disease ◽  
Pulmonary Arterial ◽  
Novel Therapeutic

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.

scholarly journals Function of Adipose-Derived Mesenchymal Stem Cells in Monocrotaline-Induced Pulmonary Arterial Hypertension through miR-191 via Regulation of BMPR2

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Caixin Zhang ◽  
Pengbo Wang ◽  
Anaz Mohammed ◽  
Zhewen Zhou ◽  
Shuwen Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Underlying Mechanism ◽  
Treated Group ◽  
Therapeutic Strategies ◽  
Protective Effects ◽  
Pulmonary Arterial

Pulmonary arterial hypertension (PAH) is a serious condition. However, prevailing therapeutic strategies are not effective enough to treat PAH. Therefore, finding an effective therapy is clearly warranted. Adipose-derived mesenchymal stem cells (ASCs) and ASCs-derived exosomes (ASCs-Exos) exert protective effects in PAH, but the underlying mechanism remains unclear. Using a coculture of ASCs and monocrotaline pyrrole (MCTP)-treated human pulmonary artery endothelial cells (HPAECs), we demonstrated that ASCs increased cell proliferation in MCTP-treated HPAECs. Results showed that ASCs-Exos improved proliferation of both control HPAECs and MCTP-treated HPAECs. In addition, by transfecting ASCs with antagomir we observed that low exosomal miR-191 expression inhibited HPAECs proliferation whereas the agomir improved. Similar results were observed in vivo using a monocrotaline (MCT)-induced PAH rat model following ASCs transplantation. And ASCs transplantation attenuated MCT-induced PAH albeit less than the antagomir treated group. Finally, we found that miR-191 repressed the expression of bone morphogenetic protein receptor 2 (BMPR2) in HPAECs and PAH rats. Thus, we conjectured that miR-191, in ASCs and ASCs-Exos, plays an important role in PAH via regulation of BMPR2. These findings are expected to contribute to promising therapeutic strategies for treating PAH in the future.

scholarly journals The challenges in paediatric pulmonary arterial hypertension

2014 ◽  
Vol 23 (134) ◽  
pp. 498-504 ◽  
Author(s):  
Maurice Beghetti ◽  
Rolf M.F. Berger
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Paediatric Population ◽  
Walking Distance ◽  
Therapeutic Approaches ◽  
End Points ◽  
Mortality And Morbidity ◽  
Optimal Dosing ◽  
Pulmonary Arterial ◽  
Randomised Controlled

Pulmonary arterial hypertension (PAH) is a rare, progressive disease affecting both adults and children. While overall survival has improved in recent years, the need for improved therapeutic approaches remains. Treatments for paediatric PAH have not yet been sufficiently examined, particularly regarding potential toxicities and optimal dosing, and there is a lack of appropriate clinical trial end-points and validated treatment goals that might enable a goal-oriented therapeutic approach. Adult randomised controlled trials in PAH are demonstrating a shift towards more long-term designs, focusing on mortality and morbidity end-points rather than changes in 6-min walking distance. However, such trial designs may not be feasible within the paediatric setting due to challenges such as sufficient recruitment and retention of paediatric patients. Consideration should, therefore, be given towards identifying optimal end-points for the paediatric population, allowing sufficient duration to evaluate efficacy and safety of potential treatments.Herein we consider some of the complexities involved in the management of paediatric PAH, specifically presenting diagnostic challenges as well as reflecting on the lack of evidence currently available to support various therapeutic approaches within the paediatric population.

scholarly journals Strategy of medical treatment of pulmonary arterial hypertension in the current international recommendations

2016 ◽  
Vol 13 (2) ◽  
pp. 46-64
Author(s):  
T V Martyniuk ◽  
I E Chazova
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Optimal Choice ◽  
New Drugs ◽  
Reverse Remodeling ◽  
Significant Progress ◽  
European Respiratory Society ◽  
Specific Therapy ◽  
Pulmonary Arterial ◽  
European Society Of Cardiology

Significant progress in the treatment of pulmonary arterial hypertension (PAH), in recent years, is associated with the introduction into clinical practice of a number of drugs pathogenetic action, can cause vasodilation and reverse remodeling of pulmonary vessels. Recently PAH-specific therapy was replenished with new drugs. This review is created as a result of the analysis of modern American recommendations CHEST and recommendations of the European society of cardiology and the European respiratory society (ESC/ERS) in order to provide all professionals involved in the maintenance of the PAH, data on the main approaches to the pharmacotherapy and the optimal choice of pharmacological treatment methods.

scholarly journals Role of Store-Operated Ca2+ Entry in the Pulmonary Vascular Remodeling Occurring in Pulmonary Arterial Hypertension

Biomolecules ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1781
Author(s):  
Bastien Masson ◽  
David Montani ◽  
Marc Humbert ◽  
Véronique Capuano ◽  
Fabrice Antigny
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Therapeutic Potential ◽  
Therapeutic Approaches ◽  
Pulmonary Vessel ◽  
Pulmonary Vascular Remodeling ◽  
Pulmonary Arterial ◽  
Arterial Tone ◽  
Ca2 Channels

Pulmonary arterial hypertension (PAH) is a severe and multifactorial disease. PAH pathogenesis mostly involves pulmonary arterial endothelial and pulmonary arterial smooth muscle cell (PASMC) dysfunction, leading to alterations in pulmonary arterial tone and distal pulmonary vessel obstruction and remodeling. Unfortunately, current PAH therapies are not curative, and therapeutic approaches mostly target endothelial dysfunction, while PASMC dysfunction is under investigation. In PAH, modifications in intracellular Ca2+ homoeostasis could partly explain PASMC dysfunction. One of the most crucial actors regulating Ca2+ homeostasis is store-operated Ca2+ channels, which mediate store-operated Ca2+ entry (SOCE). This review focuses on the main actors of SOCE in human and experimental PASMC, their contribution to PAH pathogenesis, and their therapeutic potential in PAH.

Beyond the genome: challenges and potential for epigenetics-driven therapeutic approaches in pulmonary arterial hypertension

2020 ◽  
Vol 98 (6) ◽  
pp. 631-646
Author(s):  
Jessica Y. Hsu ◽  
Jennifer L. Major ◽  
Andrew S. Riching ◽  
Rwik Sen ◽  
Julie Pires da Silva ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Mitochondrial Dynamics ◽  
Pulmonary Arteries ◽  
Therapeutic Approaches ◽  
Pulmonary Arterial ◽  
And Migration ◽  
Epigenetic Research

Pulmonary arterial hypertension (PAH) is a devastating disease of the cardiopulmonary system caused by the narrowing of the pulmonary arteries, leading to increased vascular resistance and pressure. This leads to right ventricle remodeling, dysfunction, and eventually, death. While conventional therapies have largely focused on targeting vasodilation, other pathological features of PAH including aberrant inflammation, mitochondrial dynamics, cell proliferation, and migration have not been well explored. Thus, despite some recent improvements in PAH treatment, the life expectancy and quality of life for patients with PAH remains poor. Showing many similarities to cancers, PAH is characterized by increased pulmonary arterial smooth muscle cell proliferation, decreased apoptotic signaling pathways, and changes in metabolism. The recent successes of therapies targeting epigenetic modifiers for the treatment of cancer has prompted epigenetic research in PAH, revealing many new potential therapeutic targets. In this minireview we discuss the emergence of epigenetic dysregulation in PAH and highlight epigenetic-targeting compounds that may be effective for the treatment of PAH.

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