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201: Human cervical smooth muscle stretch increases matrix metalloproteinase secretion: a new mechanism to explain premature cervical remodeling

      Objective

      We sought to define the role of cervical smooth muscle cells (CSMC) in normal and premature cervical remodeling (PCR). Specifically, we asked 1) if primary human CSMC secrete matrix metalloproteinases (MMPs; collagen remodeling enzymes), 2) if CSMC stretch induces MMP secretion, and 3) if CSMC stretch triggers increased MMP secretion in women with a history of PCR.

      Study Design

      Using IRB approved protocols, CSMC were isolated from cervical tissue obtained prior to cerclage from 4 pregnant women (14-16wks) with a history of PCR resulting in preterm birth (PTB) <28 wks and 4 gestational-age matched controls (CTL) undergoing pregnancy termination. Immunocytochemistry for alpha-SMA, SM22 and desmin was used to identify smooth muscle cells (SMC). Cyclical stretch was applied (-13kpa, 15% elongation, 45s stretch, 15s release) for 24h using a Flexcell system and then MMP1, 2, 7, 9 and 10 concentrations in the basal media were determined by Luminex. Experiments were run in duplicate and statistical analyses included logistic regression, generalized estimated equation, ANOVA and Student’s t-test.

      Results

      SMC markers were evident before and after 24h of cyclical stretch. At baseline, CSMC secrete MMPs, predominantly MMP1 and 2 with lower levels of MMP9 and 10 and cyclic stretch significantly increased MMP2 secretion in women with a history of PCR vs CTL (p=0.003, Figure 1).

      Conclusion

      Primary human CSMC secrete MMPs, which are thought to be critical for cervical remodeling. CSMC from pregnant women with a history of PCR secrete higher levels of MMP2 in response to stretch than CTL. This abnormal CSMC stretch response, characterized by increased MMP2 secretion, may elucidate a potential mechanism in the pathophysiology of PCR and PTB.
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