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Matrix Metalloproteinases in the Urine of Patients With Pulmonary Arterial Hypertension* FREE TO VIEW

Jacques I. Benisty, MD, MPH; Judah Folkman, MD; David Zurakowski, PhD; Gwendolyn Louis; Stuart Rich, MD, FCCP; David Langleben, MD; Marsha A. Moses, PhD
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*From the Vascular Biology Program (Drs. Benisty, Folkman, Zurakowski, Moses, and Ms. Louis), The Children’s Hospital, Boston, MA; SMBD-Jewish General Hospital (Dr. Langenben), Montreal, Canada; and Rush Heart Institute (Dr. Rich), Center for Pulmonary Heart Disease, Chicago, IL.

Correspondence to: Jacques I. Benisty, MD, MPH, Karp Family Research Building, Room 11213.1, 300 Longwood Ave, Boston, MA 02115; e-mail: jacques.benisty@childrens.harvard.edu

Chest. 2005;128(6_suppl):572S. doi:10.1378/chest.128.6_suppl.572S
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Associated pulmonary arterial hypertension (APAH) is a disease of vascular remodeling of the lung involving excessive endothelial and smooth-muscle cell proliferation. We hypothesized that matrix metalloproteinases (MMPs) would be frequently detected in the urine of patients with APAH and that MMP species would correlate with disease etiology. We studied a cohort of 48 patients with APAH and 47 age- and sex-matched control subjects. We performed substrate gel electrophoresis supported by immunoblot analysis using monospecific antibodies on urine samples to detect the presence of MMPs. We collected clinical and hemodynamic data and correlated these variables to the urinary MMP pattern. We studied 35 patients with primary idiopathic pulmonary hypertension (iPAH) and 13 patients with other forms of pulmonary hypertension (APAH-other). Detection of at least one MMP species was significantly higher in the APAH group (75%) compared to normal control subjects (17%, p < 0.001). The detection of MMPs in the urine was highest in iPAH (80%). Four MMP species were highly detected in patients with APAH compared to control subjects: > 150-kd species, 140-kd species, 92-kd species (MMP-9), and 72-kd species (MMP-2). Significant differences in MMP species were observed between the iPAH and APAH-other groups, with MMP-2 observed in 60% of patients with iPAH but only 15% of APAH-other patients (p < 0.01). Urinary MMPs are detected in a significantly higher proportion of patients with APAH compared to control subjects and are likely to reflect the pulmonary vascular remodeling process. Urinary MMP species show correlation with disease etiology subtype.

Abbreviations: APAH = pulmonary arterial hypertension; iPPH = primary pulmonary hypertension; MMP = matrix metalloproteinase




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