The Cancer Paradigm of Severe Pulmonary Arterial Hypertension

Overview

Journal Am J Respir Crit Care Med

Specialty Critical Care

Date 2008 Jun 17

PMID 18556624

Citations 119

Authors

Pradeep R Rai

Carlyne D Cool

Judy A C King

Troy Stevens

Nana Burns

Robert A Winn

Michael Kasper

Norbert F Voelkel

Affiliations

Soon will be listed here.

Abstract

The plexiform lesions of severe pulmonary arterial hypertension (PAH) are similar in histologic appearance, whether the disease is idiopathic or secondary. Both forms of the disease show actively proliferating endothelial cells without evidence of apoptosis. Here, we discuss the pathobiology of the atypical, angioproliferative endothelial cells in severe PAH. The concept of the endothelial cell as a "quasi-malignant" cell provides a new framework for antiproliferative, antiangiogenic therapy in severe PAH.

Citing Articles

Interplay of Transcriptomic Regulation, Microbiota, and Signaling Pathways in Lung and Gut Inflammation-Induced Tumorigenesis.

Otalora-Otalora B, Payan-Gomez C, Lopez-Rivera J, Pedroza-Aconcha N, Arboleda-Mojica S, Aristizabal-Guzman C Cells. 2025; 14(1.

PMID: 39791702 PMC: 11720097. DOI: 10.3390/cells14010001.

Cytochrome P450-derived Epoxyeicosatrienoic Acid, the Regulation of Cardiovascular-related Diseases, and the Implication for Pulmonary Hypertension.

Lan R, Zhang M, Liu K, Meng F, Xu X, Wang C Cardiovasc Drugs Ther. 2024; .

PMID: 39652233 DOI: 10.1007/s10557-024-07655-0.

Extrapulmonary manifestations of pulmonary arterial hypertension.

Singh N, Al-Naamani N, Brown M, Long G, Thenappan T, Umar S Expert Rev Respir Med. 2024; 18(3-4):189-205.

PMID: 38801029 PMC: 11713041. DOI: 10.1080/17476348.2024.2361037.

The Cavin-1/Caveolin-1 interaction attenuates BMP/Smad signaling in pulmonary hypertension by interfering with BMPR2/Caveolin-1 binding.

Tomita S, Nakanishi N, Ogata T, Higuchi Y, Sakamoto A, Tsuji Y Commun Biol. 2024; 7(1):40.

PMID: 38182755 PMC: 10770141. DOI: 10.1038/s42003-023-05693-2.

Novel Relationship between Mitofusin 2-Mediated Mitochondrial Hyperfusion, Metabolic Remodeling, and Glycolysis in Pulmonary Arterial Endothelial Cells.

Yegambaram M, Sun X, Flores A, Lu Q, Soto J, Richards J Int J Mol Sci. 2023; 24(24).

PMID: 38139362 PMC: 10744129. DOI: 10.3390/ijms242417533.

References

Sitbon O, Humbert M, Jais X, Ioos V, Hamid A, Provencher S . Long-term response to calcium channel blockers in idiopathic pulmonary arterial hypertension. Circulation. 2005; 111(23):3105-11. DOI: 10.1161/CIRCULATIONAHA.104.488486. View

Wagenvoort C . Vasoconstrictive primary pulmonary hypertension and pulmonary veno-occlusive disease. Cardiovasc Clin. 1972; 4(2):97-113. View

Cool C, Groshong S, Oakey J, Voelkel N . Pulmonary hypertension: cellular and molecular mechanisms. Chest. 2005; 128(6 Suppl):565S-571S. DOI: 10.1378/chest.128.6_suppl.565S. View

Achcar R, Demura Y, Rai P, Taraseviciene-Stewart L, Kasper M, Voelkel N . Loss of caveolin and heme oxygenase expression in severe pulmonary hypertension. Chest. 2006; 129(3):696-705. DOI: 10.1378/chest.129.3.696. View

Brevnova E, Platoshyn O, Zhang S, Yuan J . Overexpression of human KCNA5 increases IK V and enhances apoptosis. Am J Physiol Cell Physiol. 2004; 287(3):C715-22. DOI: 10.1152/ajpcell.00050.2004. View

Crossno Jr J, Garat C, Reusch J, Morris K, Dempsey E, McMurtry I . Rosiglitazone attenuates hypoxia-induced pulmonary arterial remodeling. Am J Physiol Lung Cell Mol Physiol. 2006; 292(4):L885-97. DOI: 10.1152/ajplung.00258.2006. View

Buchynska L, Nesina I . Expression of the cell cycle regulators p53, p21(WAF1/CIP1) and p16(INK4a) in human endometrial adenocarcinoma. Exp Oncol. 2006; 28(2):152-5. View

Heissig B, Rafii S, Akiyama H, Ohki Y, Sato Y, Rafael T . Low-dose irradiation promotes tissue revascularization through VEGF release from mast cells and MMP-9-mediated progenitor cell mobilization. J Exp Med. 2005; 202(6):739-50. PMC: 2212942. DOI: 10.1084/jem.20050959. View

Xu W, Koeck T, Lara A, Neumann D, DiFilippo F, Koo M . Alterations of cellular bioenergetics in pulmonary artery endothelial cells. Proc Natl Acad Sci U S A. 2007; 104(4):1342-7. PMC: 1783136. DOI: 10.1073/pnas.0605080104. View

10.

Aldred M, Vijayakrishnan J, James V, Soubrier F, Gomez-Sanchez M, Martensson G . BMPR2 gene rearrangements account for a significant proportion of mutations in familial and idiopathic pulmonary arterial hypertension. Hum Mutat. 2006; 27(2):212-3. DOI: 10.1002/humu.9398. View

11.

Platoshyn O, Zhang S, McDaniel S, Yuan J . Cytochrome c activates K+ channels before inducing apoptosis. Am J Physiol Cell Physiol. 2002; 283(4):C1298-305. DOI: 10.1152/ajpcell.00592.2001. View

12.

Stuhmer W, Alves F, Hartung F, Zientkowska M, Pardo L . Potassium channels as tumour markers. FEBS Lett. 2006; 580(12):2850-2. DOI: 10.1016/j.febslet.2006.03.062. View

13.

Jeffery T, Upton P, Trembath R, Morrell N . BMP4 inhibits proliferation and promotes myocyte differentiation of lung fibroblasts via Smad1 and JNK pathways. Am J Physiol Lung Cell Mol Physiol. 2004; 288(2):L370-8. DOI: 10.1152/ajplung.00242.2004. View

14.

Taraseviciene-Stewart L, Nicolls M, Kraskauskas D, Scerbavicius R, Burns N, Cool C . Absence of T cells confers increased pulmonary arterial hypertension and vascular remodeling. Am J Respir Crit Care Med. 2007; 175(12):1280-9. PMC: 2176089. DOI: 10.1164/rccm.200608-1189OC. View

15.

Bonnet S, Archer S, Allalunis-Turner J, Haromy A, Beaulieu C, Thompson R . A mitochondria-K+ channel axis is suppressed in cancer and its normalization promotes apoptosis and inhibits cancer growth. Cancer Cell. 2007; 11(1):37-51. DOI: 10.1016/j.ccr.2006.10.020. View

16.

Rubin L . Primary pulmonary hypertension. Chest. 1993; 104(1):236-50. DOI: 10.1378/chest.104.1.236. View

17.

Masri F, Xu W, Comhair S, Asosingh K, Koo M, Vasanji A . Hyperproliferative apoptosis-resistant endothelial cells in idiopathic pulmonary arterial hypertension. Am J Physiol Lung Cell Mol Physiol. 2007; 293(3):L548-54. DOI: 10.1152/ajplung.00428.2006. View

18.

Morrell N, Yang X, Upton P, Jourdan K, Morgan N, Sheares K . Altered growth responses of pulmonary artery smooth muscle cells from patients with primary pulmonary hypertension to transforming growth factor-beta(1) and bone morphogenetic proteins. Circulation. 2001; 104(7):790-5. DOI: 10.1161/hc3201.094152. View

19.

Pardo L . Voltage-gated potassium channels in cell proliferation. Physiology (Bethesda). 2004; 19:285-92. DOI: 10.1152/physiol.00011.2004. View

20.

McLaughlin V, Shillington A, Rich S . Survival in primary pulmonary hypertension: the impact of epoprostenol therapy. Circulation. 2002; 106(12):1477-82. DOI: 10.1161/01.cir.0000029100.82385.58. View