Tags

Type your tag names separated by a space and hit enter

Molecular determinants of microvascular dysfunction in hypertensive pregnancy and preeclampsia.
Microcirculation 2018; :e12508M

Abstract

Preeclampsia is a pregnancy-related disorder characterized by hypertension and often fetal intrauterine growth restriction, but the underlying mechanisms are unclear. Defective placentation and apoptosis of invasive cytotrophoblasts cause inadequate remodeling of spiral arteries, placental ischemia, and reduced uterine perfusion pressure (RUPP). RUPP causes 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, and stimulates the release of proinflammatory cytokines, hypoxia-inducible factor, reactive oxygen species, and angiotensin AT1 receptor agonistic autoantibodies. These circulating factors target the vascular endothelium, smooth muscle and various components of the extracellular matrix. Generalized endotheliosis in systemic, renal, cerebral, and hepatic vessels causes decreases in endothelium-derived vasodilators such as nitric oxide, prostacyclin and hyperpolarization factor, and increases in vasoconstrictors such as endothelin-1 and thromboxane A2. Enhanced mechanisms of vascular smooth muscle contraction, such as intracellular Ca2+ , protein kinase C, and Rho-kinase cause further increases in vasoconstriction. Changes in matrix metalloproteinases and extracellular matrix cause inadequate vascular remodeling and increased arterial stiffening, leading to further increases in vascular resistance and hypertension. Therapeutic options are currently limited, but understanding the molecular determinants of microvascular dysfunction could help in the design of new approaches for the prediction and management of preeclampsia.

Authors+Show Affiliations

Vascular Surgery Research Laboratories, Division of Vascular and Endovascular Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.Vascular Surgery Research Laboratories, Division of Vascular and Endovascular Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.Vascular Surgery Research Laboratories, Division of Vascular and Endovascular Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.Vascular Surgery Research Laboratories, Division of Vascular and Endovascular Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.Vascular Surgery Research Laboratories, Division of Vascular and Endovascular Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30338879

Citation

Yu, Wentao, et al. "Molecular Determinants of Microvascular Dysfunction in Hypertensive Pregnancy and Preeclampsia." Microcirculation (New York, N.Y. : 1994), 2018, pp. e12508.
Yu W, Gao W, Rong D, et al. Molecular determinants of microvascular dysfunction in hypertensive pregnancy and preeclampsia. Microcirculation. 2018.
Yu, W., Gao, W., Rong, D., Wu, Z., & Khalil, R. A. (2018). Molecular determinants of microvascular dysfunction in hypertensive pregnancy and preeclampsia. Microcirculation (New York, N.Y. : 1994), pp. e12508. doi:10.1111/micc.12508.
Yu W, et al. Molecular Determinants of Microvascular Dysfunction in Hypertensive Pregnancy and Preeclampsia. Microcirculation. 2018 Oct 19;e12508. PubMed PMID: 30338879.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Molecular determinants of microvascular dysfunction in hypertensive pregnancy and preeclampsia. AU - Yu,Wentao, AU - Gao,Wei, AU - Rong,Dan, AU - Wu,Zhixian, AU - Khalil,Raouf A, Y1 - 2018/10/19/ PY - 2018/06/06/received PY - 2018/10/05/revised PY - 2018/10/15/accepted PY - 2020/04/19/pmc-release PY - 2018/10/20/pubmed PY - 2018/10/20/medline PY - 2018/10/20/entrez KW - endothelium KW - extracellular matrix KW - microvessels KW - placental ischemia KW - vascular smooth muscle SP - e12508 EP - e12508 JF - Microcirculation (New York, N.Y. : 1994) JO - Microcirculation N2 - Preeclampsia is a pregnancy-related disorder characterized by hypertension and often fetal intrauterine growth restriction, but the underlying mechanisms are unclear. Defective placentation and apoptosis of invasive cytotrophoblasts cause inadequate remodeling of spiral arteries, placental ischemia, and reduced uterine perfusion pressure (RUPP). RUPP causes 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, and stimulates the release of proinflammatory cytokines, hypoxia-inducible factor, reactive oxygen species, and angiotensin AT1 receptor agonistic autoantibodies. These circulating factors target the vascular endothelium, smooth muscle and various components of the extracellular matrix. Generalized endotheliosis in systemic, renal, cerebral, and hepatic vessels causes decreases in endothelium-derived vasodilators such as nitric oxide, prostacyclin and hyperpolarization factor, and increases in vasoconstrictors such as endothelin-1 and thromboxane A2. Enhanced mechanisms of vascular smooth muscle contraction, such as intracellular Ca2+ , protein kinase C, and Rho-kinase cause further increases in vasoconstriction. Changes in matrix metalloproteinases and extracellular matrix cause inadequate vascular remodeling and increased arterial stiffening, leading to further increases in vascular resistance and hypertension. Therapeutic options are currently limited, but understanding the molecular determinants of microvascular dysfunction could help in the design of new approaches for the prediction and management of preeclampsia. SN - 1549-8719 UR - https://www.unboundmedicine.com/medline/citation/30338879/Molecular_determinants_of_microvascular_dysfunction_in_hypertensive_pregnancy_and_preeclampsia L2 - https://doi.org/10.1111/micc.12508 DB - PRIME DP - Unbound Medicine ER -