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Investigative Therapies in Pulmonary Arterial Hypertension

  • Chapter
Book cover Diagnosis and Management of Pulmonary Hypertension

Part of the book series: Respiratory Medicine ((RM,volume 12))

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Abstract

Pulmonary arterial hypertension (PAH) remains a serious, life threatening disease of unclear etiology. Despite the rapid development of numerous drugs to treat the disease, no cure is presently available. New treatments for PAH that are able to reverse the abnormal pulmonary vascular remodeling that is responsible for much of this disease are badly needed. To accomplish this goal, novel therapies that target many of the dysfunctional pathways that have been identified in PAH will need to be developed. This chapter reviews many of the known alterations in gene expressions, vasoconstriction, inflammation, metabolism, and cellular proliferation that have been identified in the pathogenesis of PAH. Potential pharmacologic targets arising from these abnormalities are reviewed along with data, where available, from animal studies and small clinical trials that have attempted to treat pulmonary vascular disease through manipulation of these pathways.

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Abbreviations

5HT:

Serotonin

ACE:

Angiotensinogen-converting enzyme

ALK-1:

Activin like kinase 1

AT III:

Angiotensin III

AT-1:

Angiotensinogen receptor-1

AT-2:

Angiotensinogen receptor-2

BMPR2:

Bone morphogenetic protein receptor 2

CML:

Chronic myelogenous leukemia

COPD:

Chronic obstructive lung disease

DCA:

Dichloroacetate

DHEA:

Dehydroepiandrosterone

EIF2AK4:

Eukaryotic translation initiation factor 2 alpha kinase 4

eNOS:

Endothelial nitric oxide synthase

EPCs:

Endothelial progenitor cells

HDAC:

Histone deacetylase

HIF1α:

Hypoxia inducible factor 1α

IL-1:

Interleukin-1

IL-13:

Interleukin-13

IL-6:

Interleukin-6

KCNK3:

Potassium channel subfamily K member 3

Kv:

Voltage-gated potassium channels

miRNA:

MicroRNA

MSC:

Mesenchymal stems cells

NFAT-1:

Nuclear factor of activated T-cells 1

NO:

Nitric oxide

PAH:

Pulmonary arterial hypertension

PASMC:

Pulmonary artery smooth muscle cells

PDGF:

Platelet-derived growth factor

PGI2:

Prostacyclin

PH:

Pulmonary hypertension

PPAR γ/β:

Peroxisome proliferator-activated receptors γ/β

RAAS:

Renin–angiotensin–aldosterone system

RV:

Right ventricle

SERCA 2a:

Sarcoendoplasmic reticulum calcium transport ATPase 2a

siRNA:

Small interfering RNA

SOD2:

Superoxide dismutase 2

TGF β:

Transforming growth factor β

TKI:

Tyrosine kinase inhibitor

TRPC:

Transient receptor potential channels

TXA2:

Thromboxane

VEGF:

Vascular endothelial growth factor receptor

VEGFr:

Vascular endothelial growth factor receptor

VIP:

Vasoactive intestinal peptide

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Authors and Affiliations

  1. Pulmonary Diseases and Critical Care Medicine, Division of Pulmonary and Critical Care, Pulmonary Hypertension Center, University of South Alabama, Mastin Professional Building, 2451 Fillingim Street, Mobile, AL, 36617, USA

    Karen A. Fagan M.D.

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  1. Karen A. Fagan M.D.
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  1. Division of Pulmonary, Sleep and Critical Care Medicine, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, Rhode Island, USA

    James R. Klinger

  2. Department of Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota, USA

    Robert P. Frantz

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Fagan, K.A. (2015). Investigative Therapies in Pulmonary Arterial Hypertension. In: Klinger, J., Frantz, R. (eds) Diagnosis and Management of Pulmonary Hypertension. Respiratory Medicine, vol 12. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-2636-7_17

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  • DOI: https://doi.org/10.1007/978-1-4939-2636-7_17

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