Abstract: Slide Presentations |


Hemal J. Parekh, MD*; H. Bryant Nguyen, MD; Susan Hall, MD; Mark Rehage, MS; James D. Anholm, MD; Lennard Specht, MD; Thomas A. Linkhart, PhD
Author and Funding Information

VA Loma Linda Healthcare System, Loma Linda University Medical Center, Loma Linda, CA


Chest. 2009;136(4_MeetingAbstracts):32S-j-33S. doi:10.1378/chest.136.4_MeetingAbstracts.32S-j
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PURPOSE:  C-reactive protein (CRP), a biomarker of inflammation, has a prognostic role in cardiovascular and pulmonary diseases. Recent data suggests the proinflammatory effects of CRP on cellular functions implicated in atherosclerotic lesion formation. This raises the hypothesis of whether or not CRP actively participates in the pulmonary vascular remodeling process by inducing the production of endothelin-1 (ET-1), a potent vasoconstrictor and proliferative cytokine, and expression of adhesion molecules which could culminate in inflammatory cell recruitment and vascular injury.

METHODS:  Human pulmonary artery endothelial cells (HPAECs) were cultured in endothelial cell medium supplemented with 10% fetal bovine serum for 24 hours, after which they were incubated with 25 αg/ml of human recombinant CRP for additional 24 hours prior to measurements. Expression of vascular adhesion molecule (VCAM-1) and intercellular adhesion molecule (ICAM-1) was assessed by flow cytometry. Secretion of ET-1 into the conditioned medium was measured using a commercial enzyme immunoassay kit. HPAECs were also incubated with Interleukin- 1β (IL- 1β) (10ng/ml, 24 hours), a well-known activator of endothelial cells, which served as a positive control.

RESULTS:  Incubation of HPAECs with human recombinant CRP (25 αg/ml) for 24 hours induced a significant increase in ICAM-1 expression (from 610 to 6553 mean fluorescence intensity, p < 0.005) and VCAM-1 expression (from 212 to 303 mean fluorescence intensity, p < 0.05), as compared to control. Adhesion molecule induction was similar to that observed in endothelial cells activated with IL-1β, a positive control. Likewise, CRP potentiated the production of ET-1 from HPAECs. The levels of ET-1 secreted into the medium were significantly higher at 24 hours (control 19.94 ± 3 versus CRP 46.54 ± 18 pg/ml, p < 0.05).

CONCLUSION:  CRP induces expression of adhesion molecules and secretion of ET-1 in HPAECs. Our study provides the first evidence that CRP exerts direct proinflammatory effects on pulmonary artery endothelial cells.

CLINICAL IMPLICATIONS:  The proinflammatory effects of CRP on HPAECs may contribute to pulmonary vascular remodeling and provide new therapeutic targets in the management of pulmonary arterial hypertension.

DISCLOSURE:  Hemal Parekh, No Financial Disclosure Information; No Product/Research Disclosure Information

Tuesday, November 3, 2009

10:30 AM - 12:00 PM




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