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Novel Therapeutic Approaches for Pulmonary Arterial Hypertension
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Novel Therapeutic Approaches for Pulmonary Arterial Hypertension

A special issue of Journal of Clinical Medicine (ISSN 2077-0383).

Deadline for manuscript submissions: closed (31 January 2017)

Special Issue Editor

Assoc. Prof. Jane A. Leopold

E-Mail Website
Guest Editor
Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
Interests: pulmonary hypertension
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Pulmonary arterial hypertension (PAH) is a life-threatening cardiopulmonary disease that is characterized by hypertrophic vascular remodeling of small distal pulmonary arteries with near obliteration of the vessel lumen, increased pulmonary vascular resistance, and pulmonary artery hypertensive pressures. These adverse hemodynamic parameters affect right ventricular-pulmonary artery coupling and ultimately lead to right ventricular failure and premature death. Advances have been made in contemporary pharmacotherapies with combination drugs, including agents that target the nitric oxide, prostacyclin, and endothelin signaling pathways. Despite this, patients continue to have progression of disease with adverse clinical events and outcomes. This has led to the search for novel and innovative therapeutic interventions to target the pulmonary vasculature, the right ventricle or both. Studies to identify novel disease mediators have become a priority and include next generation genetic sequencing, metabolomic profiling, and proteomic analyses. Other advances in the field involve utilizing data from these studies for gene therapies that can be delivered using aerosol, intravenous, or intracoronary delivery approaches. Cell therapy has been another area of active interest, especially with respect to treating the right ventricle. Other therapy in the early days of investigation is pulmonary artery denervation, which denervates the large pulmonary arteries to decrease sympathetic tone and, thereby, promote vasorelaxation. Together these and other novel therapies will advance the field and modify the pulmonary vascular and right ventricular disease pathophenotype to improve clinical outcomes.

Assoc. Prof. Jane A. Leopold
Guest Editor

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Keywords

  • Pulmonary arterial hypertension
  • Right ventricular dysfunction
  • Whole genome sequencing/whole exome sequencing
  • Metabolomic profiling and metabolic modulators
  • Proteomic analysis
  • Gene therapy
  • Cell therapy
  • Chemotherapeutic agents
  • Pulmonary artery denervation

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Published Papers (4 papers)

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Review

6 pages, 345 KiB  
Review
Nanoparticle-Mediated Drug Delivery System for Pulmonary Arterial Hypertension
by Kazufumi Nakamura, Hiromi Matsubara, Satoshi Akagi, Toshihiro Sarashina, Kentaro Ejiri, Norifumi Kawakita, Masashi Yoshida, Toru Miyoshi, Atsuyuki Watanabe, Nobuhiro Nishii and Hiroshi Ito
J. Clin. Med. 2017, 6(5), 48; https://doi.org/10.3390/jcm6050048 - 29 Apr 2017
Cited by 28 | Viewed by 7134
Abstract
Nanoparticles have been used as a novel drug delivery system. Drug-incorporated nanoparticles for local delivery might optimize the efficacy and minimize the side effects of drugs. The efficacy and safety of intratracheal administration of prostacyclin analog (beraprost) -incorporated nanoparticles and imatinib (a PDGF-receptor [...] Read more.
Nanoparticles have been used as a novel drug delivery system. Drug-incorporated nanoparticles for local delivery might optimize the efficacy and minimize the side effects of drugs. The efficacy and safety of intratracheal administration of prostacyclin analog (beraprost) -incorporated nanoparticles and imatinib (a PDGF-receptor tyrosine kinase inhibitor) -incorporated nanoparticles in Sugen-hypoxia-normoxia or monocrotaline rat models of pulmonary arterial hypertension (PAH) and in human PAH-pulmonary arterial smooth muscle cells have been reported. The use of inhaled drug-incorporated nanoparticles might be a novel approach for the treatment of PAH. Full article
(This article belongs to the Special Issue Novel Therapeutic Approaches for Pulmonary Arterial Hypertension)
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31 pages, 1627 KiB  
Review
Emerging Metabolic Therapies in Pulmonary Arterial Hypertension
by Lloyd D. Harvey and Stephen Y. Chan
J. Clin. Med. 2017, 6(4), 43; https://doi.org/10.3390/jcm6040043 - 4 Apr 2017
Cited by 44 | Viewed by 10079
Abstract
Pulmonary hypertension (PH) is an enigmatic vascular disorder characterized by pulmonary vascular remodeling and increased pulmonary vascular resistance, ultimately resulting in pressure overload, dysfunction, and failure of the right ventricle. Current medications for PH do not reverse or prevent disease progression, and current [...] Read more.
Pulmonary hypertension (PH) is an enigmatic vascular disorder characterized by pulmonary vascular remodeling and increased pulmonary vascular resistance, ultimately resulting in pressure overload, dysfunction, and failure of the right ventricle. Current medications for PH do not reverse or prevent disease progression, and current diagnostic strategies are suboptimal for detecting early-stage disease. Thus, there is a substantial need to develop new diagnostics and therapies that target the molecular origins of PH. Emerging investigations have defined metabolic aberrations as fundamental and early components of disease manifestation in both pulmonary vasculature and the right ventricle. As such, the elucidation of metabolic dysregulation in pulmonary hypertension allows for greater therapeutic insight into preventing, halting, or even reversing disease progression. This review will aim to discuss (1) the reprogramming and dysregulation of metabolic pathways in pulmonary hypertension; (2) the emerging therapeutic interventions targeting these metabolic pathways; and (3) further innovation needed to overcome barriers in the treatment of this devastating disease. Full article
(This article belongs to the Special Issue Novel Therapeutic Approaches for Pulmonary Arterial Hypertension)
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Graphical abstract

22 pages, 1320 KiB  
Review
The Changing Landscape of Pulmonary Arterial Hypertension in the Adult with Congenital Heart Disease
by Alexandra C. Van Dissel, Barbara J. M. Mulder and Berto J. Bouma
J. Clin. Med. 2017, 6(4), 40; https://doi.org/10.3390/jcm6040040 - 30 Mar 2017
Cited by 17 | Viewed by 9057
Abstract
Pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD) is a common type of pulmonary arterial hypertension (PAH) and a frequent complication of congenital heart disease (CHD). PAH-CHD represents a heterogeneous patient population and it is important to distinguish between the underlying cardiac [...] Read more.
Pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD) is a common type of pulmonary arterial hypertension (PAH) and a frequent complication of congenital heart disease (CHD). PAH-CHD represents a heterogeneous patient population and it is important to distinguish between the underlying cardiac defects considering the prognostic and therapeutic implications. Improved interventional techniques have enabled repair or palliation of most cardiac defects, though a substantial number of patients remain at high risk for PAH after closure. Traditionally, the treatment and management of PAH-CHD patients has been limited to palliative and supportive care, and based on expert opinion rather than clinical trials. Recently, however, the availability of advanced PAH-specific treatment has opened up a new field for the clinical management of this condition. Nevertheless, there is limited evidence on the optimal therapeutic approach for PAH-CHD. Herein, we discuss the current and novel therapeutic options for PAH-CHD as well as highlight several challenges in the clinical management at present. Full article
(This article belongs to the Special Issue Novel Therapeutic Approaches for Pulmonary Arterial Hypertension)
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Figure 1

15 pages, 226 KiB  
Review
A Review of Targeted Pulmonary Arterial Hypertension-Specific Pharmacotherapy
by Ali Ataya, Jessica Cope and Hassan Alnuaimat
J. Clin. Med. 2016, 5(12), 114; https://doi.org/10.3390/jcm5120114 - 6 Dec 2016
Cited by 13 | Viewed by 5884
Abstract
Significant advances in the understanding of the pathophysiology of pulmonary arterial hypertension over the past two decades have led to the development of targeted therapies and improved patient outcomes. Currently, a broad armamentarium of pulmonary arterial hypertension-specific drugs exists to assist in the [...] Read more.
Significant advances in the understanding of the pathophysiology of pulmonary arterial hypertension over the past two decades have led to the development of targeted therapies and improved patient outcomes. Currently, a broad armamentarium of pulmonary arterial hypertension-specific drugs exists to assist in the treatment of this complex disease state. In this manuscript, we provide a comprehensive review of the current Food and Drug Administration (FDA)-approved pulmonary arterial hypertension-specific therapies, and their supporting evidence for adults, targeting the nitric oxide, soluble guanylate cyclase, endothelin, and prostacyclin pathways. Full article
(This article belongs to the Special Issue Novel Therapeutic Approaches for Pulmonary Arterial Hypertension)
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