Endothelial dysfunction in COVID-19: an overview of evidence, biomarkers, mechanisms and potential therapies

Acta Pharmacologica Sinica, Journal Year: 2022, Volume and Issue: 44(4), P. 695 - 709

Published: Oct. 17, 2022

Language: Английский

---

Endothelial Glycocalyx Degradation in Critical Illness and Injury

Frontiers in Medicine, Journal Year: 2022, Volume and Issue: 9

Published: July 8, 2022

The endothelial glycocalyx is a gel-like layer on the luminal side of blood vessels that composed glycosaminoglycans and proteins tether them to plasma membrane. Interest in its properties function has grown, particularly last decade, as importance barrier come light. Endothelial studies have revealed many critical illnesses result degradation or removal, contributing dysfunction break-down. Loss facilitates direct access immune cells deleterious agents (e.g., proteases reactive oxygen species) endothelium, can then further cell injury leading complications such edema, thrombosis. Here, we briefly describe primary components thought be directly responsible for degradation. We review recent literature relevant damage several (sepsis, COVID-19, trauma diabetes) share inflammation common denominator with actions by (hyaluronidases, proteases, species, etc.). Finally, cover strategies therapies show promise protecting helping rebuild steroids, protease inhibitors, anticoagulants resuscitation strategies.

Language: Английский

---

Endotheliopathy in Acute COVID-19 and Long COVID

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(9), P. 8237 - 8237

Published: May 4, 2023

The pulmonary endothelium is a highly regulated organ that performs wide range of functions under physiological and pathological conditions. Since endothelial dysfunction has been demonstrated to play direct role in sepsis acute respiratory distress syndrome, its COVID-19 also extensively investigated. Indeed, apart from the COVID-19-associated coagulopathy biomarkers, new biomarkers were recognised early during pandemic, including markers cell activation or injury. We systematically searched literature up 10 March 2023 for studies examining association between long severity outcomes biomarkers.

Language: Английский

---

Role of Endothelium in Cardiovascular Sequelae of Long COVID

Biomedicines, Journal Year: 2023, Volume and Issue: 11(8), P. 2239 - 2239

Published: Aug. 9, 2023

The global action against coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2 infection, shed light on endothelial dysfunction. Although primarily affects the pulmonary system, multiple studies have documented pan-vascular involvement in COVID-19. virus is able to penetrate barrier, damaging it directly or indirectly and causing endotheliitis multi-organ injury. Several mechanisms cooperate development of dysfunction, including cell injury pyroptosis, hyperinflammation cytokine storm syndrome, oxidative stress reduced nitric oxide bioavailability, glycocalyx disruption, hypercoagulability, thrombosis. After acute-phase some patients reported signs symptoms a systemic disorder known as long COVID, which broad range cardiovascular (CV) disorders emerged. To date, exact pathophysiology COVID remains unclear: addition persistence infection mechanisms, specific pathways CV damage been postulated, such persistent viral reservoirs heart an autoimmune response cardiac antigens through molecular mimicry. aim this review provide overview main patterns enduring activation following offer latest summary complications COVID.

Language: Английский

---

Coagulation Disorders in Sepsis and COVID-19—Two Sides of the Same Coin? A Review of Inflammation–Coagulation Crosstalk in Bacterial Sepsis and COVID-19

Journal of Clinical Medicine, Journal Year: 2023, Volume and Issue: 12(2), P. 601 - 601

Published: Jan. 11, 2023

Sepsis is a major cause of morbidity and mortality worldwide. Sepsis-associated coagulation disorders are involved in the pathogenesis multiorgan failure lead to subsequently worsening prognosis. Alongside global impact COVID-19 pandemic, great number research papers have focused on SARS-CoV-2 treatment. Significant progress has been made this regard disturbances were once again found underlie some most serious adverse outcomes infection, such as acute lung injury dysfunction. In attempt untangling mechanisms behind COVID-19-associated coagulopathy (CAC), series similarities with sepsis-induced (SIC) became apparent. Whether they are, fact, same disease not established yet. The clinical picture CAC shows unique feature an initial phase intravascular confined respiratory system. Only later on, patients can develop clinically significant form systemic coagulopathy, possibly consumptive pattern, but, unlike SIC, it key feature. Deepening our understanding remain goal for community, order design validate accurate definitions classification criteria.

Language: Английский

---

Alterations in heparan sulfate proteoglycan synthesis and sulfation and the impact on vascular endothelial function

Matrix Biology Plus, Journal Year: 2022, Volume and Issue: 16, P. 100121 - 100121

Published: Sept. 7, 2022

The glycocalyx attached to the apical surface of vascular endothelial cells is a rich network proteoglycans, glycosaminoglycans, and glycoproteins with instrumental roles in homeostasis. Given their molecular complexity ability interact intra- extracellular environment, heparan sulfate proteoglycans uniquely contribute glycocalyx's role regulating permeability, mechanosignaling, ligand recognition by cognate cell receptors. Much attention has recently been devoted enzymatic shedding from its impact on function. However, other modifications are possible may have equal or complementary clinical significance. In this narrative review, we focus putative mechanisms driving non-proteolytic changes proteoglycan expression alterations sulfation side chains within glycocalyx. We then discuss how these specific function highlight therapeutic strategies target potentially reverse pathologic changes.

Language: Английский

---

Progressive differentiation toward the long-lived plasma cell compartment in the bone marrow

The Journal of Experimental Medicine, Journal Year: 2022, Volume and Issue: 220(2)

Published: Dec. 14, 2022

The longevity of plasma cells is dependent on their ability to access and reside in so-called niches that are predominantly located the bone marrow. Here, by employing a traceable method label recently generated cells, we showed homeostatic marrow spleen were continuously replenished newly B220hiMHC-IIhi populations progressively differentiated into B220loMHC-IIlo long-lived cell (LLPC) populations. We also found that, marrow, germinal center (GC)–independent GC-dependent decayed similarly upon NP-CGG engagement, both entered LLPC pool. Compared with NP+B220hiMHC-IIhi NP+B220loMHC-IIlo more immobilized better survival potential. Thus, our results suggest adhesion status dynamically altered during differentiation associated provision signals.

Language: Английский

---

Vascular Endothelial Glycocalyx Damage and Potential Targeted Therapy in COVID-19

Cells, Journal Year: 2022, Volume and Issue: 11(12), P. 1972 - 1972

Published: June 19, 2022

COVID-19 is a highly infectious respiratory disease caused by new coronavirus known as SARS-CoV-2. characterized progressive failure resulting from diffuse alveolar damage, inflammatory infiltrates, endotheliitis, and pulmonary systemic coagulopathy forming obstructive microthrombi with multi-organ dysfunction, indicating that endothelial cells (ECs) play central role in the pathogenesis of COVID-19. The glycocalyx defined complex gel-like layer glycosylated lipid–protein mixtures, which surrounds all living acts buffer between cell extracellular matrix. (EGL) plays an important vascular homeostasis via regulating permeability, adhesion, mechanosensing for hemodynamic shear stresses, antithrombotic anti-inflammatory functions. Here, we review findings described EGL damage ARDS, coagulopathy, multisystem associated Mechanistically, mediators, reactive oxygen species (ROS), matrix metalloproteases (MMPs), fragments, viral proteins may contribute to In addition, potential therapeutic strategies targeting treatment severe are summarized discussed.

Language: Английский

---

Biomarkers of endothelial dysfunction are associated with poor outcome in COVID‐19 patients: A systematic review and meta‐analysis

Reviews in Medical Virology, Journal Year: 2023, Volume and Issue: 33(4)

Published: March 21, 2023

Abstract Numerous studies have linked coronavirus disease 2019 (COVID‐19) with endothelial dysfunction and reported elevated levels of biomarkers in this disease. We conducted a systematic review meta‐analysis the published evidence respect. A literature search PubMed Scopus databases was performed to find investigating COVID‐19 patients. Pooled standardized mean differences their 95% confidence intervals were calculated for each biomarker using random effect model. 74 7668 patients included. In comparison good outcome, those poor outcome had higher von Willebrand factor (vWF) (SMD: 0.83, CI: 0.59–1.07, p < 0.00001), vWF:ADAMTS13 (1.23, (0.77–1.7), angiopoietin‐2 (Ang‐2) (1.06 (0.6–1.51), 0.0001), E‐selectin (1.09 (0.55–1.63), P‐selectin (0.59 (0.24–0.94), = 0.001), syndecan‐1 (0.99 (0.6–1.37), mid‐regional pro‐adrenomedullin (MR‐proADM) (1.52 (1.35–1.68), vascular growth (0.27 (0.02–0.53), 0.03), soluble fms‐like tyrosine kinase‐1 (sFLT‐1) (1.93 (0.65–3.21), 0.03) lower ADAMTS13 antigen (−0.69 (−0.9 −0.47) 0.00001) activity (−0.84 (−1.06 −0.61) 0.0000). Plasminogen activator inhibitor‐1 tissue plasminogen not different between two groups ( 0.05). There indicating possible role severity prognosis. particular, MR‐proADM, vWF, sFLT‐1 showed significant association these

Language: Английский

---

Myocardial Oedema as a Consequence of Viral Infection and Persistence—A Narrative Review with Focus on COVID-19 and Post COVID Sequelae

Viruses, Journal Year: 2024, Volume and Issue: 16(1), P. 121 - 121

Published: Jan. 14, 2024

Microvascular integrity is a critical factor in myocardial fluid homeostasis. The subtle equilibrium between capillary filtration and lymphatic removal disturbed during pathological processes leading to inflammation, but also hypoxia or due alterations vascular perfusion coagulability. degradation of the glycocalyx as main component endothelial barrier well pericyte disintegration results accumulation interstitial intracellular water. Moreover, dysfunction evokes an increase metabolic waste products, cytokines inflammatory cells space contributing oedema formation. This leads stiffness impaired contractility, eventually resulting cardiomyocyte apoptosis, remodelling fibrosis. following article reviews pathophysiological including myocarditis, ischaemia-reperfusion injury viral infections with special focus on pathomechanisms evoked by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In addition, clinical implications potential long-term effects persistence (long COVID), treatment options, are discussed.

Language: Английский

---