Mechanisms of Endothelial Dysfunction in Hypertensive Pregnancy and Preeclampsia
Autor: | Raouf A. Khalil, Jose S. Possomato-Vieira |
---|---|
Rok vydání: | 2016 |
Předmět: |
Vascular Endothelial Growth Factor A
0301 basic medicine Placental growth factor medicine.medical_specialty Endothelium Placenta Vasodilation 030204 cardiovascular system & hematology Article Preeclampsia Proinflammatory cytokine 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Pre-Eclampsia Ischemia Pregnancy Internal medicine medicine Animals Humans Endothelial dysfunction Hypoxia Angiotensin II receptor type 1 business.industry Hypertension Pregnancy-Induced medicine.disease Vascular endothelial growth factor 030104 developmental biology medicine.anatomical_structure Endocrinology chemistry Immunology Female Endothelium Vascular Reactive Oxygen Species business |
Popis: | Preeclampsia is a pregnancy-related disorder characterized by hypertension and could lead to maternal and fetal morbidity and mortality. Although the causative factors and pathophysiological mechanisms are unclear, endothelial dysfunction is a major hallmark of preeclampsia. Clinical tests and experimental research have suggested that generalized endotheliosis in the systemic, renal, cerebral, and hepatic circulation could decrease endothelium-derived vasodilators such as nitric oxide, prostacyclin, and hyperpolarization factor and increase vasoconstrictors such as endothelin-1 and thromboxane A2, leading to increased vasoconstriction, hypertension, and other manifestation of preeclampsia. In search for the upstream mechanisms that could cause endothelial dysfunction, certain genetic, demographic, and environmental risk factors have been suggested to cause abnormal expression of uteroplacental integrins, cytokines, and matrix metalloproteinases, leading to decreased maternal tolerance, apoptosis of invasive trophoblast cells, inadequate spiral arteries remodeling, reduced uterine perfusion pressure (RUPP), and placental ischemia/hypoxia. RUPP may cause imbalance between the antiangiogenic factors soluble fms-like tyrosine kinase-1 and soluble endoglin and the proangiogenic factors vascular endothelial growth factor and placental growth factor, or stimulate the release of other circulating bioactive factors such as inflammatory cytokines, hypoxia-inducible factor-1, reactive oxygen species, and angiotensin AT1 receptor agonistic autoantibodies. These circulating factors could then target endothelial cells and cause generalized endothelial dysfunction. Therapeutic options are currently limited, but understanding the factors involved in endothelial dysfunction could help design new approaches for prediction and management of preeclampsia. |
Databáze: | OpenAIRE |
Externí odkaz: |