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Original Research: PULMONARY VASCULAR DISEASE |

Increased Expression of Growth Differentiation Factor-15 in Systemic Sclerosis-Associated Pulmonary Arterial Hypertension

Christina A. Meadows, MS; Michael G. Risbano, MD; Li Zhang, MS; Mark W. Geraci, MD; Rubin M. Tuder, MD; David H. Collier, MD; Todd M. Bull, MD
Author and Funding Information

From the Division of Pulmonary Sciences and Critical Care Medicine (Mss Meadows and Zhang and Drs Risbano, Geraci, Tuder, and Bull), and the Division of Rheumatology (Dr Collier), Department of Medicine, University of Colorado Denver, Denver, CO.

Correspondence to: Todd M. Bull, MD, Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado, Campus Box C272, Aurora, CO 80045; e-mail: Todd.Bull@UCDenver.edu


Funding/Support: This work was supported by a grant from the National Institutes of Health [Grant 5 K08 HL072858-02] and a grant from the Scleroderma Foundation [Grant PN200509-021], both awarded to Dr Bull.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).


© 2011 American College of Chest Physicians


Chest. 2011;139(5):994-1002. doi:10.1378/chest.10-0302
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Background:  Growth differentiation factor (GDF)-15 is a secreted member of the transforming growth factor-β cytokine superfamily. GDF-15 levels are elevated in the serum of patients with cardiovascular diseases. We hypothesized that GDF-15 levels would also be increased in the plasma and lung tissue of patients with systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH).

Methods:  GDF-15 levels were measured in plasma in subjects with SSc-PAH (n = 30) and compared with subjects with systemic sclerosis (SSc) without pulmonary arterial hypertension (PAH) (n = 24). Patients with idiopathic PAH (IPAH) (n = 44) and normal individuals (n = 13) served as control subjects. Immunohistochemistry and immunofluorescence assay identified GDF-15 protein in lung tissue from patients with SSc-PAH and IPAH.

Results:  Patients with SSc-PAH had significantly higher mean circulating levels of GDF-15 in plasma compared with patients with SSc without PAH (422.3 ± 369.5 pg/mL vs 108.1 ± 192.8 pg/mL, P = .004). GDF-15 levels correlated positively with estimated right ventricular systolic pressure on echocardiogram and plasma levels of the amino terminal propeptide form of brain natriuretic peptide. There was an inverse correlation between circulating GDF-15 and diffusing capacity of the lung for carbon monoxide (Dlco) and a positive correlation with the FVC to Dlco ratio on pulmonary function test. GDF-15 levels > 125 pg/mL were associated with reduced survival. GDF-15 protein expression was increased in lung tissue from patients with SSc-PAH.

Conclusions:  GDF-15 may be a useful biomarker in PAH associated with SSc. Its presence in lung tissue may suggest a role in the pathology of the disease.

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