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Preeclampsia is a hypertensive disorder that causes complications for 1 out of 4,000 women during pregnancy. It usually arises during the second half of the pregnancy and develops into eclampsia and HELLP syndrome[1]. Eclampsia is described as a minute convulsion or fit in the mother’s arms, legs, neck or jaw that can occur from week 20 onwards. Other symptoms include severe headaches and heart burn, vision problems, lower rib pains, nausea and edema[2]. The cause of preeclampsia has not been established, however it has been theorised that it is due to a fault with nutrition and toxin transfer across the placenta.

This indicates the extracellular membrane (ECM) and glycocalyx are major players as they maintain physiological vascular tone and suitable intercellular interactions[3]. The extracellular matrix is formed of structural proteins, proteoglycans and glycosaminoglycans; and the glycocalyx consists of proteoglycans and glycoproteins. Hyaluronic acid is a crucial structural component in the extracellular matrix and glycocalyx. In the extracellular matrix, hyaluronic acid develops non-covalent interactions with small proteoglycans that stabilises the dimensional structure of the extracellular matrix[4]. While in glycocalyx, a layer of hyaluronic acid is in constant dynamic interaction with the blood[5]. Stimuli can alter the composition of these structures consequently disturbing homeostasis.

Causes[edit]

There has yet to be a definite cause of preeclampsia, but known health factors can increase the risk such as:

Preeclampsia has been theorized as the result of an impaired trophoblast invasion into the uterine spiral arteries causing ischemia[6]. Ischemic lesions can initiate the development of a systemic inflammatory response (SIR) and endothelial dysfunction representative of eclampsia[6]. This underdeveloped tissue is thought to be the result of a mechanotransduction; as the glycocalyx function is to convert biomechanical and biochemical signals into the endothelial cell[7]. Reduced signals can increase stress on cells activating other signalling pathways, such as endothelial NO synthase to compensated for the hemodynamic load[8].

The physiological conditions of hyaluronic acid synthesis and degradation are in balance through the regulation of hyaluronan synthases and hyaluronidases[9][10]. Within cells, specific localisation and pH ranges generate hyaluronic acid of different molecular weights[11]. Alterations to these conditions can alter the hyaluronic acid produced resulting in different molecular weight hyaluronic acid. For example, high molecular weight hyaluronic acid binds and inhibits the activity of extracellular serine protease which degrades the extracellular matrix and glycocalyx. Whereas, low molecular weight hyaluronic acid induces the activation of protease-activated receptors disrupting intercellular contacts[12].


Diagnosis[edit]

Patients with suspected preeclampsia have three different methods of diagnosis. One uses blood pressure readings of systolic and diastolic pressure to check for high blood pressure. Readings above systolic pressure: 140mmHg and diastolic pressure: 90mmHg are considered high blood pressure. Another is a urine test to check for protein levels and content, which require testing facilities. The final one is a blood test, which specifically checks for placental growth factor (PIGF). A high reading is a negative result.

Treatment[edit]

No cure for preeclampsia is known, however steps are taken to reduce the risk. After assessment, regular check-ups or required hospital stay with close monitoring are implemented. During this time, medication to lower blood pressure is available, as are anticonvulsants.

History[edit]

Pregnancies with headaches, heaviness and convulsion described in 400 BC by Hippocrates may have been the first recording of preeclampsia-eclampsia[13]. Centuries later in 1739, Bossier de Sauvages differentiated between eclampsia and epilepsy seizures. Following Sauvages, the combined research of Demanet (1797), Pierre Rayer (1840) and John Lever (1843) established hallmark symptoms[13]. The invention of the mercury manometer by Scipione Riva-Rocci is the diagnostic tool for preeclampsia[13].

  1. ^ Hofmann-Kiefer, K. (2013). "Placental syncytiotrophoblast maintains a specific type of glycocalyx at the fetomaternal border: the glycocalyx at the fetomaternal interface in healthy women and patients with HELLP syndrome". Reprod Sci. 20 (10): 1237–45.
  2. ^ NHS, Preeclampsia,7 June 2018, URL:https://www.nhs.uk/conditions/pre-eclampsia/
  3. ^ Harrison, D. (2011). "Inflammation, Immunity and Hypertension ". Hypertension. 57 (2): 132–140.
  4. ^ Karbownik, M. (2016). "Hyaluronan: towards novel anti-cancer therapeutics". Pharmacol. Rep. 65 (5): 1056–74. {{cite journal}}: Cite has empty unknown parameter: |1= (help)
  5. ^ Alphonsus, C. (2014). "The endothelial glycocalyx: a review of the vascular barrier". Anaesthesia. 69 (7): 777–84.
  6. ^ a b Ziganshina, M. (2016). "Hyaluronic acid in Vascular and Immune Homeostasis during Normal Pregnancy and Preeclampsia". Acta Naturae. 8 (3): 59–71.
  7. ^ Kolárová, H. (2014). "Modulation of Endothelial Glycocalyx Structure under Inflammatory Conditions". Mediators Inflamm. 2014. {{cite journal}}: Cite has empty unknown parameter: |1= (help)
  8. ^ Markos, F. (2013). "What is the mechanism of flow-mediated arterial dilatation". Clin.Exp.Pharmacol.Physiol. 40 (8): 489–94. {{cite journal}}: Cite has empty unknown parameter: |1= (help)
  9. ^ Lipowsky, H. (2012). "The Endothelial Glycocalyx as a Barrier to Leukocyte Adhesion and its Mediation by Extracellular Proteases". Biomed. Eng. 40 (4): 840–48.
  10. ^ Salmon, A. (2012). "Loss of the Endothelial Glycocalyx Links Albuminuria and Vascular Dysfunction". J Am Soc Nephrol. 23 (8): 1339–50. {{cite journal}}: Cite has empty unknown parameter: |1= (help)
  11. ^ Lennon, F. (2011). "Hyaluronan regulation of vascular integrity". Cardiovasc. Dis. 1 (3): 200–213.
  12. ^ Mambetsariev, N. (2010). "HABP2 is a Novel Regulator of Vascular Integrity". Arterioscler Thromb Vasc Biol. 30 (3): 483–90.
  13. ^ a b c Bell, M. (2020). "2,400 Years of Preeclampsia History". Preeclampsia Foundation.
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