Volume 11: Issue 1

This issue of Advances is about looking forward, but I'd like to start by looking backward for some perspective. About 10 years ago, a small company called Actelion launched the first effective oral therapy for pulmonary arterial hypertension, bosentan, while another startup, United Therapeutics, launched subcutaneous treprostinil. Rather suddenly, our patients had 2 options other than intravenous epoprostenol, and a broader number of cardiology and pulmonary physicians became interested in recognizing, evaluating, and treating patients with pulmonary hypertension. Since that time, an enormous investment from industry partners and governmental authorities around the world has resulted in significant rewards.

Mary Bartlett, PNP-BC*

Winthrop University HospitalMineola, NY

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Anticoagulation, particularly warfarin, is often used in patients with pulmonary arterial hypertension (PAH). There is evidence that abnormalities of blood coagulation factors contribute to a prothrombotic state in patients with PAH.1 Warfarin is the most widely prescribed anticoagulant for the prevention and treatment of arterial and venous thromboembolic diseases. Newer medications such as dabigatran or rivaroxaban, which do not require laboratory monitoring, have not been studied in the pulmonary hypertension population.

Warfarin therapy is complicated by a narrow therapeutic

This article is intended to deliver a clinically relevant overview about the role of coagulation factors and platelets in the pathogenesis of pulmonary hypertension. After summarizing the available data with warfarin, some information is provided about the novel oral anticoagulants that were recently approved for atrial fibrillation and may soon be approved for venous thrombosis. The author is hopeful that this information will stimulate investigator interest in this topic and drive us toward meaningful studies about this important aspect of PAH therapy.

For more than 60 years, researchers have sought to understand the molecular basis of idiopathic pulmonary arterial hypertension (PAH). Recognition of the heritable form of the disease led to the creation of patient registries in the 1980s and 1990s, and discovery of BMPR2 as the cause of roughly 80% of heritable PAH in 2000. With discovery of the disease gene came opportunity for intervention, with focus on 2 alternative approaches. First, it may be possible to correct the effects of BMPR2 mutation directly through interventions targeted at correction of trafficking defects, increasing expression of the unmutated allele, and correction of splicing defects. Second, therapeutic interventions are being targeted at the signaling consequences of BMPR2 mutation. In particular, therapies targeting cytoskeletal and metabolic defects caused by BMPR2 mutation are currently in trials, or will be ready for human trials in the near future. Translation of these findings into therapies is the culmination of decades of research, and holds great promise for treatment of the underlying molecular bases of disease.

Pulmonary arterial hypertension (PAH) presents a challenging problem for health care providers, as effective long-term therapies have been elusive. An emerging paradigm for the pathogenesis of PAH is that endothelial cell injury and apoptosis at the level of the precapillary arteriole could be the initiating event in the pathogenesis of this disease. This hypothesis has spurred research on novel regenerative approaches using stem and progenitor cells. In this review, we compare findings from the latest preclinical and clinical studies using endothelial progenitor cell (EPC) and mesenchymal stem cell (MSC) therapy to treat PAH. Additionally, we highlight recent advances in gene-enhanced cell therapy, an approach that promises to augment the therapeutic potential of EPCs and MSCs especially for the reversal of established PAH. These new regenerative approaches have shown great promise in preclinical studies; however, large, rigorously designed clinical studies will be necessary to establish clinical efficacy.

Bridging the gap

Guest Editor's Memo

The Role of Warfarin Anticoagulation in Pulmonary Hypertension

Mary Bartlett, PNP-BC*

Thrombin and Platelets in Pulmonary Hypertension: A Lot More Than Clot

Potential Interventions Against BMPR2-Related Pulmonary Hypertension

Cell Therapy for Pulmonary Arterial Hypertension: Potential Efficacy of Endothelial Progenitor Cells and Mesenchymal Stem Cells

Imatinib: A Perspective on Its Potential for PAH Patients

Optimal Timing for Lung Transplantation: Why Not Include RVEF As an Indicator?

Review of the Latest Published Research

The Use of cMRI to Evaluate Patients with PAH

Conference Abstracts

Guest Editor’s Memo

A Roundtable Discussion Addressing Patient-Centered Care and Quality of Life in Patients With Pulmonary Arterial Hypertension

Editor’s Memo

Pulmonary Hypertension Associated With Parenchymal Lung Disease