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Novel Strategy for Treatment of Pulmonary Arterial Hypertension: Enhancement of Apoptosis

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Abstract

Advanced pulmonary arterial hypertension is characterized by extensive vascular remodeling that is usually resistant to vasodilator therapy. As the major component of the vascular media, decreased apoptosis of pulmonary arterial smooth muscle cell (PASMC) plays key roles during pulmonary vascular remodeling. Recent studies showed that enhancement of apoptosis of PASMC can reverse pulmonary vascular remodeling and severe pulmonary arterial hypertension. Enhancement of apoptosis of PASMC is becoming a novel strategy to reverse severe pulmonary arterial hypertension. This review analyzes some potential strategies to reverse pulmonary vascular remodeling.

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Abbreviations

AP-1:

Activating protein-1

ASK1:

Apoptosis signal-regulating kinase 1

AVD:

Apoptotic volume decrease

BMP:

Bone morphogenetic protein

BMPR2:

Bone morphogenetic protein receptor 2

[Ca2+]SR:

[Ca2+] in the sarcoplasmic reticulum (SR)

Cyt c :

Cytochrome c

DCA:

Dichloroacetate

eNOS:

Endothelial nitric oxide synthase

ERM:

Ezrin–radirin–moesin

GTP:

Guanosine triphosphate

GTPase:

Guanosine triphosphatase

H2O2 :

Hydrogen peroxide

IP3:

Inositol 1,4,5-trisphosphate

[Ca2+]i :

Intracellular free Ca2+ concentration

[K+]i :

Intracellular K+

IK(V):

K+ current through KV channels

DCm:

Mitochondrial membrane potential

MPT:

Mitochondrial permeability transition

NO:

Nitric oxide

NF-κB:

Nuclear factor kappa B

PAH:

Pulmonary arterial hypertension

PAP:

Pulmonary arterial pressure

PASMC:

Pulmonary arterial smooth muscle cell

PPARgamma:

Peroxisome proliferator-activated receptor gamma

SMC:

Smooth muscle cell

TNF-α:

Tumor necrosis factor α

VSMC:

Vascular smooth muscle cell

Kv :

Voltage-gated K+

HMG-CoA:

3-Hydroxy-3-methylglutaryl-coenzyme A

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Acknowledgments

This study was supported by the National Natural Science Foundation of China (Grant No. 30972958).

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Authors and Affiliations

  1. Pediatric Center of Cardiac Surgery, Cardiovascular Institute and Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 167 Beilishi Road, 100037, Beijing, China

    Jing-bin Huang, Ying-long Liu, Xiao-dong Lv, Kong Bo & Xiang-ming Fan

  2. Department of Cardiovascular and Thoracic Surgery, First Affiliated Hospital of Sun Yat-Sen University, 510080, Guangzhou, China

    Pei-wu Sun

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  2. Ying-long Liu
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  3. Pei-wu Sun
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  4. Xiao-dong Lv
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  5. Kong Bo
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  6. Xiang-ming Fan
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Correspondence to Ying-long Liu.

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Huang, Jb., Liu, Yl., Sun, Pw. et al. Novel Strategy for Treatment of Pulmonary Arterial Hypertension: Enhancement of Apoptosis. Lung 188, 179–189 (2010). https://doi.org/10.1007/s00408-010-9233-8

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  • DOI: https://doi.org/10.1007/s00408-010-9233-8

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