0
Articles |

Microsatellite Mutational Analysis of Endothelial Cells Within Plexiform Lesions From Patients With Familial, Pediatric, and Sporadic Pulmonary Hypertension*

Michael E. Yeager, BS; Heiko. A. Golpon, MD; Norbert F. Voelkel, MD; Rubin M. Tuder, MD
Author and Funding Information

*From the Pulmonary Hypertension Center, Division of Pulmonary Sciences, Departments of Medicine and Pathology, University of Colorado Health Sciences Center, Denver CO.

Correspondence to: Michael E. Yeager, BS, Graduate Student, Department of Pathology, University of Colorado Health Sciences Center, Box B216, 4200 E. 9th Ave, Denver, CO 80262; e-mail: mike.yeager@uchsc.edu



Chest. 2002;121(3_suppl):61S. doi:10.1378/chest.121.3_suppl.61S
Text Size: A A A
Published online

Extract

Severe pulmonary hypertension (PH) is characterized by elevated pulmonary artery pressures leading to right-heart failure, yet the pathogeneses of familial PH, pediatric PH, and sporadic PH (SPH) are poorly understood. We previously demonstrated monoclonal proliferation of endothelial cells (ECs) within plexiform lesions in primary SPH, and we showed that plexiform ECs display dysregulated gene expression compared to normal pulmonary ECs arranged in monolayers. We posited that mutations in genes controlling EC growth and death might drive monoclonal EC growth in plexiform lesions. Using polymerase chain reaction, we found microsatellite instability within the hMSH2 mismatch repair gene and frameshift mutation within the transforming growth factor-β receptor type II (TGF-β RII) and Bax genes. Specifically, we show genetic instability in 13 patients with primary SPH (6 of 19 lesions TGF-β RII; 4 of 19 lesions Bax) and in 1 patient with primary pediatric PH (2 of 5 lesions hMSH2), but not in 5 patients with familial PH (0 of 16 lesions) nor in 10 normal lungs. EC monoclonality, when performed, correlated tightly with occurrence of mutation (three of three primary SPH patients). Immunohistochemistry revealed absence of TGF-β RII, hMSH2, and hMLH1 expression in plexiform lesion ECs of SPH tissues compared to ECs in normal pulmonary arteries from both normal and PH patients. To our knowledge, this is the first report of mutation within ECs outside the setting of neoplasia. Our observations may assist in subclassification of PH patients as well as point to future novel therapeutic interventions.

First Page Preview

View Large
First page PDF preview

Sign In to Access Full Content

MEMBER & INDIVIDUAL SUBSCRIBER

Want Access?

NEW TO CHEST?

Become a CHEST member and receive a FREE subscription as a benefit of membership.

Individuals can purchase this article on ScienceDirect.

Individuals can purchase a subscription to the journal.

Individuals can purchase a subscription to the journal or buy individual articles.

Learn more about membership or Purchase a Full Subscription.

INSTITUTIONAL ACCESS

Institutional access is now available through ScienceDirect and can be purchased at myelsevier.com.

Sign In to Access Full Content

MEMBER & INDIVIDUAL SUBSCRIBER

Want Access?

NEW TO CHEST?

Become a CHEST member and receive a FREE subscription as a benefit of membership.

Individuals can purchase this article on ScienceDirect.

Individuals can purchase a subscription to the journal.

Individuals can purchase a subscription to the journal or buy individual articles.

Learn more about membership or Purchase a Full Subscription.

INSTITUTIONAL ACCESS

Institutional access is now available through ScienceDirect and can be purchased at myelsevier.com.

Figures

Tables

References

NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Some tools below are only available to our subscribers or users with an online account.

Sign In to Access Full Content

MEMBER & INDIVIDUAL SUBSCRIBER

Want Access?

NEW TO CHEST?

Become a CHEST member and receive a FREE subscription as a benefit of membership.

Individuals can purchase this article on ScienceDirect.

Individuals can purchase a subscription to the journal.

Individuals can purchase a subscription to the journal or buy individual articles.

Learn more about membership or Purchase a Full Subscription.

INSTITUTIONAL ACCESS

Institutional access is now available through ScienceDirect and can be purchased at myelsevier.com.

Related Content

Customize your page view by dragging & repositioning the boxes below.

Find Similar Articles
CHEST Journal Articles
  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543