Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Spielhofer, M.
Endotheliale Dysfunktion: Überblick und aktueller Ausblick in der Entstehung von Präeklampsie
Humanmedizin; [ Diplomarbeit ] Medizinische Universität Graz; 2022. pp. 68
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Cervar-Zivkovic Mila
- Goswami Nandu
- Altmetrics:
- Abstract:
- Introduction: Pre-eclampsia is a multisystem disorder that combines elevated blood pressure over 140/90 mmHg with proteinuria or any other manifestations. Although pre-eclampsia (PE) is a major threat to maternal and foetal well-being all over the world, its development has not been understood well yet. Placental maladaptation and a disturbed remodelling of uterine arteries cause reduced uteroplacental perfusion (RUPP). As a result, placental ischemia occurs and stimulates the expression of bioactive factors, producing an imbalance between pro- and anti-angiogenic factors. Furthermore, it triggers an inflammatory response and oxidative stress, and subsequent endothelial damage and dysfunction. Consequently, this leads to generalized endotheliosis, in systemic, hepatic, renal and cerebral blood vessels, leading to an imbalance of vasoconstrictors and vasodilators and causing hypertension. In conclusion, the pathogenesis of PE is a multifactorial event, whose understanding is from great importance for prevention, diagnosis and future therapeutical options, as they are still very limited for now. Objectives: The aim of this work is to give an overview on the current literature of the pathogenesis of PE, regarding endothelial dysfunction and hypertension. Methodology: A systematic literature research on endothelial dysfunction in pre-eclamptic patients was conducted. Only articles published in the past five years were included to really focus on the newest insights into this topic. Results: The literature search resulted in 903 articles, of which 40 publications met all the inclusion criteria and were selected. Discussion: Present findings demonstrate an interaction of several factors in the pathogenesis of PE : RUPP changes the expression of bioactive factors like sFlt-1, VEGF, PlGF, as well as CAMs, causing an imbalance in the pro- and anti-angiogenic metabolism. Additionally, proinflammatory cytokines, like CRP and interleukins and reactive oxygen species, are released, damaging the endothelium, smooth muscle cells and the glycocalyx. Furthermore, studies presented a decreased NO bioavailability, causing impaired vasodilatation. Enhanced intracellular Ca2+ stimulates contraction in smooth muscle cells, increasing vasoconstriction further. Dyslipidaemia and changes in the complements system also seem to play a part in the pathophysiology. New indicators for diagnosis and/or possible therapeutical targets include lipocalin-2, sAxl, galectin-3 microRNA and HtrA4. Compromised functions of matrix metalloproteinases cause arterial stiffness and inadequate vascular remodelling, leading to hypertension. Concluding this new found data, future directions could include an adjustment of diagnosis criteria, new therapeutical targets, earlier diagnosis and better prevention.