Rho A/Rho kinase: human umbilical artery mRNA expression in normal and pre eclamptic pregnancies and functional role in isoprostane-induced vasoconstriction

Friel, Anne M.; Sexton, Donal J.; O’Reilly, Michael; Smith, Terry J.; Morrison, John J.

doi:10.1530/rep.1.01088

Cited by 20 publications

(13 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The importance of Rho in PE is supported by a study comparing subcutaneous resistance arteries from PE, Norm-Preg and nonpregnant women, and showing that Ca 2+ sensitivity of the contractile elements is increased in women with PE (VanWijk et al, 2002). Other studies have shown that mRNA expression of Rho-kinase is downregulated in umbilical arteries of PE women (Friel, 2006). Stimulation of AT 1 R may induce upregulation of RhoA/ROCK activity in hypertensive rats (Kataoka et al, 2002).…”

Section: Introductionmentioning

confidence: 90%

Vascular and Cellular Calcium in Normal and Hypertensive Pregnancy

Adamová¹,

Ozkan²,

Khalil³

2009

CCP

View full text Add to dashboard Cite

Normal pregnancy is associated with significant hemodynamic changes in the cardiovascular system in order to meet the metabolic demands of mother and fetus. These changes include increased cardiac output, decreased vascular resistance, and vascular remodeling in the uterine and systemic circulation. Preeclampsia (PE) is a major complication of pregnancy characterized by proteinuria and hypertension. Several risk factors have been implicated in the pathogenesis of PE including genetic and dietary factors. Ca 2+ is an essential dietary element and an important regulator of many cellular processes including vascular function. The importance of adequate dietary Ca 2+ intake during pregnancy is supported by many studies. Pregnancy-associated changes in Ca 2+ metabolism and plasma Ca 2+ have been observed. During pregnancy, changes in intracellular free Ca 2+ concentration ([Ca 2+ ] i ) have been described in red blood cells, platelets and immune cells. Also, during pregnancy, an increase in [Ca 2+ ] i in endothelial cells (EC) stimulates the production of vasodilator substances such as nitric oxide and prostacyclin. Normal pregnancy is also associated with decreased vascular smooth muscle (VSM) [Ca 2+ ] i and possibly the Ca 2+ -sensitization pathways of VSM contraction including protein kinase C, Rho-kinase, and mitogen-activated protein kinase. Ca 2+ -dependent matrix metalloproteinases could also promote extracellular matrix degradation and vascular remodeling during pregnancy. Disruption in the balance between dietary, plasma and vascular cell Ca 2+ may be responsible for some of the manifestation of PE including procoagulation, decreased vasodilation, and increased vasoconstriction and vascular resistance. The potential benefits of Ca 2+ supplements during pregnancy, and the use of modulators of vascular Ca 2+ to reduce the manifestations of PE in susceptible women remain an important area for experimental and clinical research.

show abstract

Section: Introductionmentioning

confidence: 90%

Vascular and Cellular Calcium in Normal and Hypertensive Pregnancy

Adamová¹,

Ozkan²,

Khalil³

2009

CCP

View full text Add to dashboard Cite

show abstract

“…352 However, some studies show decreased expression of Rho-kinase in umbilical arteries of preeclamptic women. 359 …”

Section: Mmps and Vascular Dysfunction In Hypertensive Pregnancy Amentioning

confidence: 99%

Matrix Metalloproteinases in Normal Pregnancy and Preeclampsia

Chen

Khalil

2017

Progress in Molecular Biology and Translational Science

234

168

View full text Add to dashboard Cite

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.

show abstract

“…Inhibition of Rho-kinase reduces TXA 2 -induced contraction in uterine vessels of non-pregnant rats [156]. However, some studies show decreased expression of Rho-kinase in umbilical arteries of PE women [191]. …”

Section: Introductionmentioning

confidence: 99%

Bioactive factors in uteroplacental and systemic circulation link placental ischemia to generalized vascular dysfunction in hypertensive pregnancy and preeclampsia

Shah

Khalil

2015

Biochemical Pharmacology

153

124

View full text Add to dashboard Cite

Preeclampsia is a pregnancy-associated disorder characterized by hypertension, and could lead to maternal and fetal morbidity and mortality; however, the pathophysiological mechanisms involved are unclear. Predisposing demographic, genetic and environmental risk factors could cause localized abnormalities in uteroplacental cytoactive factors such as integrins, matrix metalloproteinases, cytokines and major histocompatibility complex molecules leading to decreased vascular remodeling, uteroplacental vasoconstriction, trophoblast cells apoptosis, and abnormal development of the placenta. Defective placentation and decreased trophoblast invasion of the myometrium cause reduction in uteroplacental perfusion pressure (RUPP) and placental ischemia/hypoxia, an important event in preeclampsia. RUPP could stimulate the release of circulating bioactive factors such as the anti-angiogenic factors soluble fms-like tyrosine kinase-1 and soluble endoglin that cause imbalance with the pro-angiogenic factors vascular endothelial growth factor and placental growth factor, or cause the release of inflammatory cytokines, reactive oxygen species, hypoxia-induced factor-1 and AT1 angiotensin receptor agonistic autoantibodies. The circulating bioactive factors target endothelial cells causing generalized endotheliosis, endothelial dysfunction, decreased vasodilators such as nitric oxide and prostacyclin and increased vasoconstrictors such as endothelin-1 and thromboxane A2, leading to increased vasoconstriction. The bioactive factors also stimulate the mechanisms of VSM contraction including Ca2+, protein kinase C, and Rho-kinase and induce extracellular matrix remodeling leading to further vasoconstriction and hypertension. While therapeutic options are currently limited, understanding the underlying mechanisms could help design new interventions for management of preeclampsia.

show abstract

Rho A/Rho kinase: human umbilical artery mRNA expression in normal and pre eclamptic pregnancies and functional role in isoprostane-induced vasoconstriction

Cited by 20 publications

References 26 publications

Vascular and Cellular Calcium in Normal and Hypertensive Pregnancy

Vascular and Cellular Calcium in Normal and Hypertensive Pregnancy

Matrix Metalloproteinases in Normal Pregnancy and Preeclampsia

Bioactive factors in uteroplacental and systemic circulation link placental ischemia to generalized vascular dysfunction in hypertensive pregnancy and preeclampsia

Contact Info

Product

Resources

About