State-of-the-Art Paper
Inflammation, Growth Factors, and Pulmonary Vascular Remodeling

https://doi.org/10.1016/j.jacc.2009.04.006Get rights and content
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Inflammatory processes are prominent in various types of human and experimental pulmonary hypertension (PH) and are increasingly recognized as major pathogenic components of pulmonary vascular remodeling. Macrophages, T and B lymphocytes, and dendritic cells are present in the vascular lesions of PH, whether in idiopathic pulmonary arterial hypertension (PAH) or PAH related to more classical forms of inflammatory syndromes such as connective tissue diseases, human immunodeficiency virus (HIV), or other viral etiologies. Similarly, the presence of circulating chemokines and cytokines, viral protein components (e.g., HIV-1 Nef), and increased expression of growth (such as vascular endothelial growth factor and platelet-derived growth factor) and transcriptional (e.g., nuclear factor of activated T cells or NFAT) factors in these patients are thought to contribute directly to further recruitment of inflammatory cells and proliferation of smooth muscle and endothelial cells. Other processes, such as mitochondrial and ion channel dysregulation, seem to convey a state of cellular resistance to apoptosis; this has recently emerged as a necessary event in the pathogenesis of pulmonary vascular remodeling. Thus, the recognition of complex inflammatory disturbances in the vascular remodeling process offers potential specific targets for therapy and has recently led to clinical trials investigating, for example, the use of tyrosine kinase inhibitors. This paper provides an overview of specific inflammatory pathways involving cells, chemokines and cytokines, cellular dysfunctions, growth factors, and viral proteins, highlighting their potential role in pulmonary vascular remodeling and the possibility of future targeted therapy.

Key Words

growth factors
inflammation
pulmonary vascular remodeling

Abbreviations and Acronyms

AECA
anti-endothelial cell antibody
bcl
B-cell lymphoma
COPD
chronic obstructive pulmonary disease
EC
endothelial cell
EGF
epidermal growth factor
ET
endothelin
HCV
hepatitis C virus
HHV
human herpes virus
HIV
human immunodeficiency virus
5-HT
serotonin
5-HTT
serotonin transporter
IL
interleukin
IPAH
idiopathic pulmonary arterial hypertension
Kv
voltage-dependent potassium channel
MCT
monocrotaline
mRNA
messenger ribonucleic acid
NFAT
nuclear factor of activated T cells
PA
pulmonary artery
PAH
pulmonary arterial hypertension
PCR
polymerase chain reaction
PDGF
platelet-derived growth factor
PDGFR
platelet-derived growth factor receptor
PH
pulmonary hypertension
RV
right ventricular
SIV
simian immunodeficiency virus
SMC
smooth muscle cell
SSc
systemic sclerosis
TGF
transforming growth factor
TN
tenascin
TNF
tumor necrosis factor
VEGF
vascular endothelial growth factor

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