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Defective placentation and apoptosis of invasive cytotrophoblasts cause inadequate remodeling of spiral arteries, placental ischemia, and reduced uterine perfusion pressure (\n                    <jats:styled-content style=\"fixed-case\">RUPP<\/jats:styled-content>\n                    ).\n                    <jats:styled-content style=\"fixed-case\">RUPP<\/jats:styled-content>\n                    causes imbalance between the anti\u2010angiogenic factors soluble fms\u2010like tyrosine kinase\u20101 and soluble endoglin and the pro\u2010angiogenic vascular endothelial growth factor and placental growth factor, and stimulates the release of proinflammatory cytokines, hypoxia\u2010inducible factor, reactive oxygen species, and angiotensin\n                    <jats:styled-content style=\"fixed-case\">AT<\/jats:styled-content>\n                    <jats:sub>1<\/jats:sub>\n                    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\u2010derived vasodilators such as nitric oxide, prostacyclin and hyperpolarization factor, and increases in vasoconstrictors such as endothelin\u20101 and thromboxane A2. Enhanced mechanisms of vascular smooth muscle contraction, such as intracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    , protein kinase C, and Rho\u2010kinase 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.\n                  <\/jats:p>","DOI":"10.1111\/micc.12508","type":"journal-article","created":{"date-parts":[[2018,10,19]],"date-time":"2018-10-19T08:24:35Z","timestamp":1539937475000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Molecular determinants of microvascular dysfunction in hypertensive pregnancy and preeclampsia"],"prefix":"10.1111","volume":"26","author":[{"given":"Wentao","family":"Yu","sequence":"first","affiliation":[{"name":"Vascular Surgery Research Laboratories Division of Vascular and Endovascular Surgery Brigham and Women's Hospital Harvard Medical School Boston 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