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The matrix metalloproteases and endothelin-1 in infection-associated preterm birth.

Olgun NS, Reznik SE - Obstet Gynecol Int (2010)

Bottom Line: While the risk factors for PTB are numerous, the single most common cause is intrauterine infection.As there is currently no FDA-approved therapy for infection-associated PTB, understanding the pathogenesis of preterm labor (PTL) and delivery should be given high priority.Several lines of evidence also suggest a role for endothelin-1 (ET-1) in infection-associated preterm delivery.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Sciences, College of Pharmacy and Allied Health Professions, St. John's University, St. Albert Hall G018-B, 8000 Utopia Parkway, Jamaica, NY 11439, USA.

ABSTRACT
Preterm birth (PTB) is clinically defined as any delivery which occurs before the completion of 37 weeks of gestation, and is currently the most important problem in obstetrics. In the United States, PTB accounts for 12-13% of all live births, and, with the exception of fetuses suffering from anomalies, is the primary cause of perinatal mortality. While the risk factors for PTB are numerous, the single most common cause is intrauterine infection. As there is currently no FDA-approved therapy for infection-associated PTB, understanding the pathogenesis of preterm labor (PTL) and delivery should be given high priority. The matrix metalloproteinases (MMPs) are a family of enzymes that have been implicated in normal parturition as well as infection-triggered rupture of membranes and preterm birth. Several lines of evidence also suggest a role for endothelin-1 (ET-1) in infection-associated preterm delivery. This paper focuses on the evidence that the MMPs and ET-1 act in the same molecular pathway in preterm birth.

No MeSH data available.


Related in: MedlinePlus

Effect of the MMP inhibitor GM6001 on preterm delivery in the mouse model. (a) Incidence of preterm delivery in the mouse model in either the absence (control group) or presence (study group) of GM6001 after i.p. 3.3 mg/kg LPS injection (P < .01, Fisher's exact test).  (b) Change in LPS injection-to-delivery time interval in hours, in the control group versus study group (P < .005, Mann-Whitney test).
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fig1: Effect of the MMP inhibitor GM6001 on preterm delivery in the mouse model. (a) Incidence of preterm delivery in the mouse model in either the absence (control group) or presence (study group) of GM6001 after i.p. 3.3 mg/kg LPS injection (P < .01, Fisher's exact test). (b) Change in LPS injection-to-delivery time interval in hours, in the control group versus study group (P < .005, Mann-Whitney test).

Mentions: In 2007, we tested the nonspecific MMP inhibitor GM6001 (EMD Biosciences, La Jolla, CA) for its effect on endotoxin-triggered preterm labor in a mouse model [54]. GM6001 has Ki values for MMP-1, -2, -3, -8, and -9 which are in the nanomolar-to-picomolar range. Briefly, pregnant C57Bl/6 mice were injected with LPS on gestational days 15.5–16 in order to simulate infection-associated PTB and then received either GM6001 (study group) or vehicle (control group) 12 hours later. In the GM6001 group there was a significant decrease in the number of mice delivering prematurely when compared to the controls (Figure 1), suggesting that one or more of the MMPs are critical in the pathogenesis of infection-associated PTB.


The matrix metalloproteases and endothelin-1 in infection-associated preterm birth.

Olgun NS, Reznik SE - Obstet Gynecol Int (2010)

Effect of the MMP inhibitor GM6001 on preterm delivery in the mouse model. (a) Incidence of preterm delivery in the mouse model in either the absence (control group) or presence (study group) of GM6001 after i.p. 3.3 mg/kg LPS injection (P < .01, Fisher's exact test).  (b) Change in LPS injection-to-delivery time interval in hours, in the control group versus study group (P < .005, Mann-Whitney test).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2913859&req=5

fig1: Effect of the MMP inhibitor GM6001 on preterm delivery in the mouse model. (a) Incidence of preterm delivery in the mouse model in either the absence (control group) or presence (study group) of GM6001 after i.p. 3.3 mg/kg LPS injection (P < .01, Fisher's exact test). (b) Change in LPS injection-to-delivery time interval in hours, in the control group versus study group (P < .005, Mann-Whitney test).
Mentions: In 2007, we tested the nonspecific MMP inhibitor GM6001 (EMD Biosciences, La Jolla, CA) for its effect on endotoxin-triggered preterm labor in a mouse model [54]. GM6001 has Ki values for MMP-1, -2, -3, -8, and -9 which are in the nanomolar-to-picomolar range. Briefly, pregnant C57Bl/6 mice were injected with LPS on gestational days 15.5–16 in order to simulate infection-associated PTB and then received either GM6001 (study group) or vehicle (control group) 12 hours later. In the GM6001 group there was a significant decrease in the number of mice delivering prematurely when compared to the controls (Figure 1), suggesting that one or more of the MMPs are critical in the pathogenesis of infection-associated PTB.

Bottom Line: While the risk factors for PTB are numerous, the single most common cause is intrauterine infection.As there is currently no FDA-approved therapy for infection-associated PTB, understanding the pathogenesis of preterm labor (PTL) and delivery should be given high priority.Several lines of evidence also suggest a role for endothelin-1 (ET-1) in infection-associated preterm delivery.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Sciences, College of Pharmacy and Allied Health Professions, St. John's University, St. Albert Hall G018-B, 8000 Utopia Parkway, Jamaica, NY 11439, USA.

ABSTRACT
Preterm birth (PTB) is clinically defined as any delivery which occurs before the completion of 37 weeks of gestation, and is currently the most important problem in obstetrics. In the United States, PTB accounts for 12-13% of all live births, and, with the exception of fetuses suffering from anomalies, is the primary cause of perinatal mortality. While the risk factors for PTB are numerous, the single most common cause is intrauterine infection. As there is currently no FDA-approved therapy for infection-associated PTB, understanding the pathogenesis of preterm labor (PTL) and delivery should be given high priority. The matrix metalloproteinases (MMPs) are a family of enzymes that have been implicated in normal parturition as well as infection-triggered rupture of membranes and preterm birth. Several lines of evidence also suggest a role for endothelin-1 (ET-1) in infection-associated preterm delivery. This paper focuses on the evidence that the MMPs and ET-1 act in the same molecular pathway in preterm birth.

No MeSH data available.


Related in: MedlinePlus