US EPA

521530 

Journal Article 

Doxycycline inhibits matrix metalloproteinase-2 neonatal pulmonary artery endothelial cells 

Shuford-Hopkins, E; Bulger, A 

2005 

Yes 

Ethnicity & Disease
ISSN: 1049-510X 

15 

3 

98-99 

English 

Persistent pulmonary hypertension of the newborn (PPHN) affects more than 10,000 infants in the United States every year. Abnormal pulmonary vascular remodeling may predispose to PPHN. Matrix metalloproteinases are a large family of zinc-dependent enzymes that are needed for cell proliferation, cell migration, and changes in the extracellular matrix. MMPs are produced by various cells (vascular smooth muscle, monocytes, endothelial) and are needed for degradation of stiff collagen fibrils; however, overexpression of MMPs can lead to heart failure. There are more than 20 different identified MMPs, which are grouped based on their function or location. MMP-2 is a gelatinase found in both vascular smooth muscle and pulmonary artery endothelial cells. MMP-2 production is required for tissue remodeling and is suspected to play a role in neonatal pulmonary vascular remodeling. Doxycycline, a member of the tetracycline family, is a commonly used antimicrobial agent. It has been shown to inhibit the activity of mammalian collagenases and gelatinases. This inhibition is unrelated to antimicrobial properties. It has been speculated that doxycycline inhibitory effects are due to reduced MMP-2 mRNA stability. We hypothesized that doxycycline will decrease MMP-2 production by neonatal porcine pulmonary artery endothelial cells.