Differential immunohistochemical expression of matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 in cow uteri with adenomyosis during follicular phase

Moreira, Lio; Carvalho, Eulógio Carlos Queiróz de; Caldas-Bussiere, M.C.

doi:10.1007/s11259-011-9470-1

Cited by 8 publications

(4 citation statements)

References 23 publications

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“…28–30,103,364 MMP-2 and MMP-9 are expressed in the bovine uterus, 365,366 and MMP-2, MMP-7 and MMP-9 are expressed in the rat uterus. 37,93 Alterations in MMP-2, MMP-7 and MMP-9 expression/activity could be involved in the endometrial changes associated with menstrual disorders and endometriosis 367,368 The plasma levels of MMP-2 and MMP-9 increase during normal pregnancy.…”

Section: Mmps and Uterine Contraction During Pregnancy And Labormentioning

confidence: 99%

Matrix Metalloproteinases in Normal Pregnancy and Preeclampsia

Chen

Khalil

2017

Progress in Molecular Biology and Translational Science

212

168

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Normal pregnancy is associated with marked hemodynamic and uterine changes that allow adequate uteroplacental blood flow and uterine expansion for the growing fetus. These pregnancy-associated changes involve significant uteroplacental and vascular remodeling. Matrix metalloproteinases (MMPs) are important regulators of vascular and uterine remodeling. Increases in MMP-2 and MMP-9 have been implicated in vasodilation, placentation and uterine expansion during normal pregnancy. The increases in MMPs could be induced by the increased production of estrogen and progesterone during pregnancy. MMP expression/activity may be altered during complications of pregnancy. Decreased vascular MMP-2 and MMP-9 may lead to decreased vasodilation, increased vasoconstriction, hypertensive pregnancy and preeclampsia. Abnormal expression of uteroplacental integrins, cytokines and MMPs may lead to decreased maternal tolerance, apoptosis of invasive trophoblast cells, inadequate remodeling of spiral arteries, and reduced uterine perfusion pressure (RUPP). RUPP may cause imbalance between the anti-angiogenic factors soluble fms-like tyrosine kinase-1 and soluble endoglin and the pro-angiogenic vascular endothelial growth factor and placental growth factor, or stimulate the release of inflammatory cytokines, hypoxia-inducible factor, reactive oxygen species, and angiotensin AT1 receptor agonistic autoantibodies. These circulating factors could target MMPs in the extracellular matrix as well as endothelial and vascular smooth muscle cells, causing generalized vascular dysfunction, increased vasoconstriction and hypertension in pregnancy. MMP activity can also be altered by endogenous tissue inhibitors of metalloproteinases (TIMPs) and changes in the MMP/TIMP ratio. In addition to their vascular effects, decreases in expression/activity of MMP-2 and MMP-9 in the uterus could impede uterine growth and expansion and lead to premature labor. Understanding the role of MMPs in uteroplacental and vascular remodeling and function could help design new approaches for prediction and management of preeclampsia and premature labor.

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Section: Mmps and Uterine Contraction During Pregnancy And Labormentioning

confidence: 99%

Matrix Metalloproteinases in Normal Pregnancy and Preeclampsia

Chen

Khalil

2017

Progress in Molecular Biology and Translational Science

212

168

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“…MMPs include collagenases, gelatinases, stromelysins, matrilysins, and membrane-type MMPs [15]. MMP-2 (gelatinase A) and MMP-9 (gelatinase B) are expressed in bovine uterus [16, 17] and play a role in endometrial tissue remodeling during the estrous cycle, menstrual cycle and pregnancy in animals and human [18-20]. Also, we have previously shown an upregulation of MMP-2 and -9 in the myometrium and aorta of normal pregnant rats, and suggested a role of MMPs in uterine and vascular remodeling [21, 22].…”

Section: Introductionmentioning

confidence: 99%

Altered matrix metalloproteinase-2 and -9 expression/activity links placental ischemia and anti-angiogenic sFlt-1 to uteroplacental and vascular remodeling and collagen deposition in hypertensive pregnancy

Mata

Mazzuca

et al. 2014

Biochemical Pharmacology

103

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Preeclampsia is a complication of pregnancy manifested as maternal hypertension and often fetal growth restriction. Placental ischemia could be an initiating event, but the linking mechanisms leading to hypertension and growth restriction are unclear. We have shown an upregulation of matrix metalloproteinases (MMPs) during normal pregnancy (Norm-Preg). To test the role of MMPs in hypertensive-pregnancy (HTN-Preg), maternal and fetal parameters, MMPs expression, activity and distribution, and collagen and elastin content were measured in uterus, placenta and aorta of Norm-Preg rats and in rat model of reduced uteroplacental perfusion pressure (RUPP). Maternal blood pressure was higher, and uterine, placental and aortic weight, and the litter size and pup weight were less in RUPP than Norm-Preg rats. Western blots and gelatin zymography revealed decreases in amount and gelatinase activity of MMP-2 and MMP-9 in uterus, placenta and aorta of RUPP compared with Norm-Preg rats. Immunohistochemistry confirmed reduced MMPs in uterus, placenta and aortic media of RUPP rats. Collagen, but not elastin, was more abundant in uterus, placenta and aorta of RUPP than Norm-Preg rats. The anti-angiogenic factor soluble fms-like tyrosine kinase-1 (sFlt-1) decreased MMPs in uterus, placenta and aorta of Norm-Preg rats, and vascular endothelial growth factor (VEGF) reversed the decreases in MMPs in tissues of RUPP rats. Thus placental ischemia and anti-angiogenic sFlt-1 decrease uterine, placental and vascular MMP-2 and MMP-9, leading to increased uteroplacental and vascular collagen, and growth-restrictive remodeling in HTN-Preg. Angiogenic factors and MMP activators may reverse the decrease in MMPs and enhance growth-permissive remodeling in preeclampsia.

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“…MMPs include collagenases, gelatinases, stromelysins, matrilysins, and membrane-type MMPs with different tissue expression, distribution and substrate specificity [6]. MMP-2 (gelatinase A) and MMP-9 (gelatinase B) are expressed in the bovine uterus [7, 8] and play a role in the endometrial tissue remodeling during normal estrous and menstrual cycles and pregnancy [9–11]. Also, we have previously shown an upregulation of MMP-2 and -9 in the myometrium of late pregnant rats, and suggested a role of MMPs in uterine tissue remodeling [12].…”

Section: Introductionmentioning

confidence: 99%

EMMPRIN-mediated induction of uterine and vascular matrix metalloproteinases during pregnancy and in response to estrogen and progesterone

Dang

Tran

et al. 2013

Biochemical Pharmacology

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Pregnancy is associated with uteroplacental and vascular remodeling in order to adapt for the growing fetus and the hemodynamic changes in the maternal circulation. We have previously shown upregulation of uterine matrix metalloproteinases (MMPs) during pregnancy. Whether pregnancy-associated changes in MMPs are localized to the uterus or are generalized in feto-placental and maternal circulation is unclear. Also, the mechanisms causing the changes in uteroplacental and vascular MMPs during pregnancy are unclear. MMPs expression, activity and tissue distribution were measured in uterus, placenta and aorta of virgin, mid-pregnant (mid-Preg) and late pregnant (late-Preg) rats. Western blots and gelatin zymography revealed increases in MMP-2 and -9 in uterus and aorta of late-Preg compared with virgin and mid-Preg rats. In contrast, MMP-2 and -9 were decreased in placenta of late-Preg versus mid-Preg rats. Extracellular MMP inducer (EMMPRIN) was increased in uterus and aorta of pregnant rats, but was less in placenta of late-Preg than mid-Preg rats. Prolonged treatment of uterus or aorta of virgin rats with 17β-estradiol and progesterone increased the amount of EMMPRIN, MMP-2 and -9, and the sex hormone-induced increases in MMPs were prevented by EMMPRIN neutralizing antibody. Immunohistochemistry revealed that MMP-2 and -9 and EMMPRIN increased in uterus and aorta of pregnant rats, but decreased in placenta of late-Preg versus mid-Preg rats. Thus pregnancy-associated upregulation of uterine MMPs is paralleled by increased vascular MMPs, and both are mediated by EMMPRIN and induced by estrogen and progesterone, suggesting similar role of MMPs in uterine and vascular tissue remodeling and function during pregnancy. The decreased MMPs and EMMPRIN in placenta of late-Preg rats suggests reduced role of MMPs in feto-placental circulation during late pregnancy.

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Differential immunohistochemical expression of matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 in cow uteri with adenomyosis during follicular phase

Cited by 8 publications

References 23 publications

Matrix Metalloproteinases in Normal Pregnancy and Preeclampsia

Matrix Metalloproteinases in Normal Pregnancy and Preeclampsia

Altered matrix metalloproteinase-2 and -9 expression/activity links placental ischemia and anti-angiogenic sFlt-1 to uteroplacental and vascular remodeling and collagen deposition in hypertensive pregnancy

EMMPRIN-mediated induction of uterine and vascular matrix metalloproteinases during pregnancy and in response to estrogen and progesterone

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