Abbreviations
ATPase: adenosine triphosphatase
BMPR2: bone morphogenetic protein receptor type 2
[Ca2+]cyt: cytosolic free Ca2+ concentration
CCB: calcium channel blocker
COPD: chronic obstructive pulmonary disease
CTEPH: chronic thromboembolic pulmonary hypertension
CYP: cytochrome P450
DAG: diacylglycerol
EC: endothelial cell
ECE: endothelin-converting enzyme
EGF: epidermal growth factor
ERA: endothelin receptor antagonist
ET: endothelin-1
FDA: Food and Drug Administration
HCN: hyperpolarization-activated cyclic nucleotide–gated
HIV: human immunodeficiency virus
HPAP: heritable pulmonary arterial hypertension
HPV: hypoxic pulmonary vasoconstriction
5HT: serotonin
IP3: inositol triphosphate
IPAH: idiopathic pulmonary arterial hypertension
IPR: prostacyclin receptor
LV: left ventricle
mGC: membrane guanylate cyclase
6MWT: six-minute walk testing
NO: nitric oxide
NO2: nitric dioxide
NYHA: New York Heart Association
PA: pulmonary artery
PAEC: pulmonary arterial endothelial cell
PAH: pulmonary arterial hypertension
Pao2: partial pressure of arterial O2
PAOP: pulmonary artery occlusion pressure
PAP: pulmonary arterial pressure
PASMC: pulmonary artery smooth muscle cell
PDE: phosphodiesterase
PDGF: platelet-derived growth factor
PGI2: prostacyclin, prostaglandin I2
PH: pulmonary hypertension
PIP2: phosphatidylinositol 4,5-biphosphate
PKA: protein kinase A
PKG: protein kinase G
PLC: phospholipase C
PVR: pulmonary vascular resistance
RAP: right atrial pressure
ROC: receptor-operated Ca2+ channel
RV: right ventricle
RVF: right ventricular failure
RVH: right ventricular hypertrophy
RVSP: right ventricular systolic pressure
sGC: soluble guanylate cyclase
SR: sarcoplasmic reticulum
SVR: systemic vascular resistance
TKR: tyrosine kinase receptor
TxA2: thromboxane A2
VDCC: voltage-dependent Ca2+ channel
VEGF: vascular endothelial growth factors
VIP: vasoactive intestinal peptide
VSM: vascular smooth muscle
The pulmonary circulation plays a unique and essential role in gas exchange and, in particular, oxygenation of venous blood. It is a low-resistance and low-pressure circulatory system; the mean PAP in a healthy man is about 12 mm Hg. PAP is a function of CO and PVR. PH is defined as the mean PAP of 25 mm Hg or greater at rest. In patients with PH, pressure overload (i.e., increased afterload) places additional stress on the RV, leading to RV dysfunction and hypertrophy, and in some cases right heart failure. Patients present with a range of symptoms, including dyspnea, fatigue, chest pain, and syncope. PH is a complication of many chronic diseases and is estimated to affect as much as 10%–20% of the general population (McLaughlin et al., 2009).
Pulmonary hypertension is a primary disorder of the pulmonary vasculature and a complication of other cardiopulmonary, vascular, and inflammatory diseases. Based on shared pathophysiological and pathological characteristics as well as response to therapies, PH can be classified into five groups (Simonneau et al., 2013):