Hyaluronic Acid in Vascular and Immune Homeostasis during Normal Pregnancy and Preeclampsia

Abstract

Preeclampsia (PE) is a multisystem pathologic state that clinically manifests itself after the 20th week of pregnancy. It is characterized by high maternal and perinatal morbidity and mortality. According to modern concepts, the impairment of trophoblast invasion into maternal spiral arteries, leading to the development of ischemia in placenta, is considered to be the major pathogenetic factor of PE development. Ischemic lesions initiate the development of a systemic inflammatory response (SIR) and endothelial dysfunction, which is the main cause of the multiple organ failure in PE. Some data has appear indicating the importance of a glycans-forming endothelial glycocalyx and extracellular matrix (ECM) for placenta morphogenesis, as well as their role in the regulation of vascular permeability and vascular tone in hypertension disorders and, in particular, PE. Since intact glycocalyx and ECM are considered to be the major factors that maintain the physiological vascular tone and adequate intercellular interactions, their value in PE pathogenesis is underestimated. This review is focused on hyaluronic acid (HA) as the key glycan providing the organization and stabilization of the ECM and glycocalyx, its distribution in tissues in the case of presence or absence of placental pathology, as well as on the regulatory function of hyaluronic acids of various molecular weights in different physiological and pathophysiological processes. The summarized data will provide a better understanding of the PE pathogenesis, with the main focus on glycopathology.

Endothelial Dysfunction as a Consequence of Endothelial Glycocalyx Damage: A Role in the Pathogenesis of Preeclampsia

“…[55]. Key eGC glycans are heparan sulfate proteoglycans (HSPGs), which compose about 50-90% of the total amount of proteoglycans present in the eGC, and HA-the main supporting glycan [14,15]. Main proteoglycans of the eGC and their characteristics are given in Table 2 (part II).…”

“…The results show an up-regulation of ICAM-1 (expression increases in 3 times) with degradation compared to non-degraded controls, and attribute this effect to a down-regulation in nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activity in response to flow; this suggests that eGC is not solely a physical barrier to adhesion but rather plays an important role in governing the phenotype of endothelial cells, a key determinant in leukocyte adhesion [82]. Other mechanisms also contribute to the initiation of lymphocytes adhesion to the endothelial cells after reduction of eGC layer: decrease of NO production, which is capable to inhibit leukocyte-endothelial cell adhesion [87]; appearance of eGC fragments, (such as low-molecular-weight HA), which show their pro-inflammatory properties, affecting the maturity of dendritic cells and stimulating them to produce cytokines [14,88]; and exposure and synthesis under inflammatory response of hypoglycosylated structures, which interact with cell adhesion molecules of leukocytes [18,89].…”

“…Their carbohydrate part contains a large amount of sialo and sulpho residues, forming overall negative charge of the endothelial cell surface. The outer segment of this layer (spreading out toward the vascular lumen), formed by the carbohydrate part of glycoconjugates, is a polysaccharide gel-eGC [14], with thickness ranging 2-4.5 μm [15] in different departments of the vascular system.…”

The Role of Interactions Between Trophoblastderived Extracellular Microvesicles, Immune Cells and Endothelium in Pathogenesis of Pre-Eclampsia

“…ст.) в сочетании с протеинурией (≥ 0,3 г в суточной моче) и нередко сопровождается отеками и полиорганной/ полисистемной дисфункцией/недостаточностью [132,182].…”

“…Данное заболевание представляет су-щественный риск развития отдаленных сердечно-сосудистых осложнений как для матери, так и для ребенка. Помимо артериальной гипертензии и протеинурии, объективным признаком ПЭ является состояние гиперкоагуляции, сосудистой дисфункции, а также избыточного (чрезмерного) системного воспалительного ответа, вызванное выбросом плацентарных провоспалительных, антиангиогенных и прокоагулянтных факторов в ответ на ишемически-реперфузионное повреждение плаценты [33,128,182].…”