Glycocalyx Degradation in Ischemia-Reperfusion Injury

Abassi, Zaid; Armaly, Zaher; Heyman, Samuel N.

doi:10.1016/j.ajpath.2019.08.019

Cited by 73 publications

(48 citation statements)

References 122 publications

(193 reference statements)

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“…The vascular endothelial glycocalyx is crucial to endothelial function [ 67 ], as it is involved in microvascular reactivity, and modulates the interaction between the endothelium and blood constituents [ 68 ]. In addition, the vascular endothelial glycocalyx protects endothelial cells from shear stress caused by blood flow, and serves as a vascular permeability barrier [ 69 ].…”

Section: Vascular Endothelial Glycocalyxmentioning

confidence: 99%

“…As shown in Fig. 3 , the intact vascular endothelial glycocalyx harbors various cytokines and chemokines, receptors, growth factors, gap junction proteins, and enzymes, including extracellular superoxide dismutase (ecSOD), endothelial nitric oxide synthase (eNOS), ACEs, lipoprotein lipase, xanthine oxidase, and antithrombin III, all of which play a central role in endothelial function and blood/microvascular/tissue interactions [ 68 ]. Vascular endothelial dysfunction and vascular failure occur in situations where the endothelial glycocalyx is impaired, which has roles in the development of various cardiovascular diseases [ 70 , 71 ].…”

Section: Vascular Endothelial Glycocalyxmentioning

confidence: 99%

“…Systemic ischemia occurs in various life-threatening clinical settings, including cardiac arrest, hemorrhagic shock during trauma, or ST-elevation myocardial infarction complicated by cardiogenic shock [ 112 , 113 ]. During these situations, distortion of the glycocalyx structure and function contributes to the multiorgan dysfunction that follows global ischemia of various etiologies, such as renal, cardiac, pulmonary, and hepatic ischemia/reperfusion injuries [ 68 , 114 ]. Damage of the vascular endothelial glycocalyx in these ischemia/reperfusion injuries is largely mediated by ROS, specifically through the activation of endothelial NADPH oxidase 2 (NOX2) and xanthine oxidase that are bound to glycosaminoglycans anchored at the endothelial surface layer [ 115 , 116 ].…”

Section: Vascular Endothelial Glycocalyx Dysfunction Induces a Severementioning

confidence: 99%

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Endothelial glycocalyx damage as a systemic inflammatory microvascular endotheliopathy in COVID-19

Yamaoka‐Tojo

2020

Biomedical Journal

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In atherosclerosis patients, vascular endothelial dysfunction is commonly observed alongside damage of the vascular endothelial glycocalyx, an extracellular matrix bound to and encapsulating the endothelial cells lining the blood vessel wall. Although atherosclerotic risk factors have been reported in severe patients with coronavirus disease 2019 (COVID-19), the exact mechanisms are unclear. The mortality associated with the COVID-19 outbreak is increased by comorbidities, including hypertension, diabetes, obesity, chronic obstructive pulmonary disease (COPD), and cardiovascular disease. Besides, older individuals and smokers have significantly worse outcomes. Interestingly, these comorbidities and risk factors are consistent with the pathophysiology that causes vascular endothelial glycocalyx damage. Moreover, vascular glycocalyx dysfunction causes microvascular leakage, which results in interstitial pulmonary abnormal shadows (multiple patchy shadows with a ground glass inter-pneumonic appearance). This is frequently followed by severe acute respiratory distress syndrome (ARDS), closely related to coagulo-fibrinolytic changes contributing to disseminated intravascular coagulation (DIC) and Kawasaki disease shock syndrome, as well as inducing activation of the coagulation cascade, leading to thromboembolism and multiple organ failure. Notably, SARS-CoV-2, the causative virus of COVID-19, binds to ACE2, which is abundantly present not only in human epithelia of the lung and the small intestine, but also in vascular endothelial cells and arterial smooth muscle cells. Moreover, COVID-19 can induce severe septic shock, and sepsis can easily lead to systemic degradation of the vascular endothelial glycocalyx. In the current review, we propose new concepts and therapeutic goals for COVID-19-related vascular endothelial glycocalyx damage, based on previous vascular endothelial medicine research.

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Section: Vascular Endothelial Glycocalyxmentioning

confidence: 99%

Section: Vascular Endothelial Glycocalyxmentioning

confidence: 99%

Section: Vascular Endothelial Glycocalyx Dysfunction Induces a Severementioning

confidence: 99%

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Endothelial glycocalyx damage as a systemic inflammatory microvascular endotheliopathy in COVID-19

Yamaoka‐Tojo

2020

Biomedical Journal

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“…There are several hypothetical mechanisms, outlined in Figure 3 , that warrant consideration. Possibly, unopposed Ang II due to depletion of cell membrane-bound ACE2 results in altered regional microcirculation and hypoxia, with the generation of reactive oxygen species and endothelial damage, glycocalyx degradation, and disseminated coagulopathy ( Abassi et al, 2020a ). This may further compromise the regional microcirculation with a feed forward loop, leading to organ failure including the heart ( Abassi et al, 2020b ), lungs ( Abassi et al, 2020d ), and kidneys ( Batlle et al, 2020 ).…”

Section: Knowledge Gaps: the Missing Pieces In The Puzzlementioning

confidence: 99%

ACE2, COVID-19 Infection, Inflammation, and Coagulopathy: Missing Pieces in the Puzzle

et al. 2020

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Engulfed by the grave consequences of the coronavirus disease 2019 (COVID-19) pandemic, a better understanding of the unique pattern of viral invasion and virulence is of utmost importance. Angiotensin (Ang)-converting enzyme (ACE) 2 is a key component in COVID-19 infection. Expressed on cell membranes in target pulmonary and intestinal host cells, ACE2 serves as an anchor for initial viral homing, binding to COVID-19 spike-protein domains to enable viral entry into cells and subsequent replication. Viral attachment is facilitated by a multiplicity of membranal and circulating proteases that further uncover attachment loci. Inherent or acquired enhancement of membrane ACE2 expression, likely leads to a higher degree of infection and may explain the predisposition to severe disease among males, diabetics, or patients with respiratory or cardiac diseases. Additionally, once attached, viral intracellular translocation and replication leads to depletion of membranal ACE2 through degradation and shedding. ACE2 generates Ang 1-7, which serves a critical role in counterbalancing the vasoconstrictive, pro-inflammatory, and pro-coagulant effects of ACE-induced Ang II. Therefore, Ang 1-7 may decline in tissues infected by COVID-19, leading to unopposed deleterious outcomes of Ang II. This likely leads to microcirculatory derangement with endothelial damage, profound inflammation, and coagulopathy that characterize the more severe clinical manifestations of COVID-19 infection. Our understanding of COVID-ACE2 associations is incomplete, and some conceptual formulations are currently speculative, leading to controversies over issues such as the usage of ACE inhibitors or Ang-receptor blockers (ARBs). This highlights the importance of focusing on ACE2 physiology in the evaluation and management of COVID-19 disease.

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“…This layer protects the endothelium from shear stress which is caused by blood flow and serves as a vascular permeability barrier. Glycocalyx damage during IR can be detected by elevated plasma levels of e.g., heparan sulfate and syndecan-1, which suggests their use as biomarkers of endothelial integrity (Abassi et al, 2020) (Figure 1).…”

Section: Stabilization Of the Endothelial Glycocalyx From Degradationmentioning

confidence: 99%

Novel Strategies for Endothelial Preservation in Lung Transplant Ischemia-Reperfusion Injury

Jungraithmayr

2020

Front. Physiol.

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Lung ischemia reperfusion (IR) injury inevitably occurs during lung transplantation. The pulmonary endothelium is the primary target of IR injury that potentially results in severe pulmonary dysfunction. Over the last decades, various molecules, receptors, and signaling pathways were identified in order to develop treatment strategies for the preservation of the pulmonary endothelium against IR injury. We here review the latest and most promising therapeutic strategies for the protection of the endothelium against IR injury. These include the stabilization of the endothelial glycocalyx, inhibition of endothelial autophagy, inhibition of adhesion molecules, targeting of angiotensin-converting enzyme, and traditional viral and novel non-viral gene transfer approaches. Though some of these strategies proved to be promising in experimental studies, very few of these treatment concepts made the transfer into clinical application. This dilemma underscores the need for more experimental evidence for the translation into clinical studies to invent therapeutic concepts against IR injury-mediated endothelial damage.

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Glycocalyx Degradation in Ischemia-Reperfusion Injury

Cited by 73 publications

References 122 publications

Endothelial glycocalyx damage as a systemic inflammatory microvascular endotheliopathy in COVID-19

Endothelial glycocalyx damage as a systemic inflammatory microvascular endotheliopathy in COVID-19

ACE2, COVID-19 Infection, Inflammation, and Coagulopathy: Missing Pieces in the Puzzle

Novel Strategies for Endothelial Preservation in Lung Transplant Ischemia-Reperfusion Injury

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