Endothelial glycocalyx regulates cytoadherence in<i>Plasmodium falciparum</i>malaria

Introini, Viola; Carciati, Antonio; Tomaiuolo, Giovanna; Cicuta, Pietro; Guido, Stefano

doi:10.1098/rsif.2018.0773

Cited by 20 publications

(22 citation statements)

References 69 publications

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“…This is shown by the presence of large vesicular nuclei, endothelial destruction, activation of transcription factor NF-κB, increased expression of cell adhesion molecules, such as ICAM-1, VCAM-1, E-selectin, cytokine release and BBB breakdown [ 35 , 57 – 62 ]. Endothelial damage in CM is also demonstrated by changes in the endothelial glycocalix upon exposure to PRBC, both in vitro [ 63 ] and in vivo in human CM [ 64 ] and murine experimental CM (eCM) [ 65 ] and release of endothelial vesicles into the circulation [ 66 ].…”

Section: Introductionmentioning

confidence: 99%

Pathophysiology and neurologic sequelae of cerebral malaria

Schiess¹,

Villabona-Rueda

Cottier

et al. 2020

Malar J

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Cerebral malaria (CM), results from Plasmodium falciparum infection, and has a high mortality rate. CM survivors can retain lifelong post CM sequelae, including seizures and neurocognitive deficits profoundly affecting their quality of life. As the Plasmodium parasite does not enter the brain, but resides inside erythrocytes and are confined to the lumen of the brain's vasculature, the neuropathogenesis leading to these neurologic sequelae is unclear and underinvestigated. Interestingly, postmortem CM pathology differs in brain regions, such as the appearance of haemorragic punctae in white versus gray matter. Various host and parasite factors contribute to the risk of CM, including exposure at a young age, parasite-and host-related genetics, parasite sequestration and the extent of host inflammatory responses. Thus far, several proposed adjunctive treatments have not been successful in the treatment of CM but are highly needed. The region-specific CM neuro-pathogenesis leading to neurologic sequelae is intriguing, but not sufficiently addressed in research. More attention to this may lead to the development of effective adjunctive treatments to address CM neurologic sequelae.

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Section: Introductionmentioning

confidence: 99%

Pathophysiology and neurologic sequelae of cerebral malaria

Schiess¹,

Villabona-Rueda

Cottier

et al. 2020

Malar J

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“…In 2018, an organ-on-chip device that mimics the lumen of a blood microvessel was described. This organ chip was used to determine the role of endothelial glycocalyx in the regulation of P. falciparum cytoadherence, supporting the proposed role of glycocalyx disruption in the pathogenesis of malarial disease [ 64 ]. Later in 2020, Arakawa et al developed a robust 3D microvessel model that emulates the arteriole–capillary–venule transition.…”

Section: Fungi and Parasitesmentioning

confidence: 93%

Refining Host-Pathogen Interactions: Organ-on-Chip Side of the Coin

Baddal

Marrazzo

2021

Pathogens

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Bioinspired organ-level in vitro platforms that recapitulate human organ physiology and organ-specific responses have emerged as effective technologies for infectious disease research, drug discovery, and personalized medicine. A major challenge in tissue engineering for infectious diseases has been the reconstruction of the dynamic 3D microenvironment reflecting the architectural and functional complexity of the human body in order to more accurately model the initiation and progression of host–microbe interactions. By bridging the gap between in vitro experimental models and human pathophysiology and providing alternatives for animal models, organ-on-chip microfluidic devices have so far been implemented in multiple research areas, contributing to major advances in the field. Given the emergence of the recent pandemic, plug-and-play organ chips may hold the key for tackling an unmet clinical need in the development of effective therapeutic strategies. In this review, latest studies harnessing organ-on-chip platforms to unravel host–pathogen interactions are presented to highlight the prospects for the microfluidic technology in infectious diseases research.

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“…It has been proposed that a breakdown of the endothelial GCX plays a key role in severe malaria. In a study by Introini et al ., 85 the interactions between Plasmodium falciparum infected red blood cells (PfRBCs) and GCX were investigated in vitro . Impairment of the GCX was obtained by enzymatic removal of sialic acid residues, which, due to their terminal location and net negative charge, are implicated in the initial interactions with contacting cells.…”

Section: Part B: the Role Of The Glycocalyx In Vascular Related Diseamentioning

confidence: 99%

“… 200 Infectious diseases including sepsis, Dengue, Zika and Corona viruses, and malaria also involve the GCX. 85 , 136 , 167 Because of increasing recognition of the role of the GCX in a wide range of diseases, there has been a vigorous search for methods to protect the GCX from degradation or to enhance its synthesis in disease environments. 200 …”

Section: Introductionmentioning

confidence: 99%

The Glycocalyx and Its Role in Vascular Physiology and Vascular Related Diseases

Weinbaum

Cancel

et al. 2020

Cardiovasc Eng Tech

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Purpose In 2007 the two senior authors wrote a review on the structure and function of the endothelial glycocalyx layer (Weinbaum in Annu Rev Biomed Eng 9:121–167, 2007). Since then there has been an explosion of interest in this hydrated gel-like structure that coats the luminal surface of endothelial cells that line our vasculature due to its important functions in (A) basic vascular physiology and (B) vascular related diseases. This review will highlight the major advances that have occurred since our 2007 paper. Methods A literature search mainly focusing on the role of the glycocalyx in the two major areas described above was performed using electronic databases. Results In part (A) of this review, the new formulation of the century old Starling principle, now referred to as the Michel–Weinbaum glycoclayx model or revised Starling hypothesis, is described including new subtleties and physiological ramifications. New insights into mechanotransduction and release of nitric oxide due to fluid shear stress sensed by the glycocalyx are elaborated. Major advances in understanding the organization and function of glycocalyx components, and new techniques for measuring both its thickness and spatio-chemical organization based on super resolution, stochastic optical reconstruction microscopy (STORM) are presented. As discussed in part (B) of this review, it is now recognized that artery wall stiffness associated with hypertension and aging induces glycocalyx degradation, endothelial dysfunction and vascular disease. In addition to atherosclerosis and cardiovascular diseases, the glycocalyx plays an important role in lifestyle related diseases (e.g., diabetes) and cancer. Infectious diseases including sepsis, Dengue, Zika and Corona viruses, and malaria also involve the glycocalyx. Because of increasing recognition of the role of the glycocalyx in a wide range of diseases, there has been a vigorous search for methods to protect the glycocalyx from degradation or to enhance its synthesis in disease environments. Conclusion As we have seen in this review, many important developments in our basic understanding of GCX structure, function and role in diseases have been described since the 2007 paper. The future is wide open for continued GCX research.

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Endothelial glycocalyx regulates cytoadherence inPlasmodium falciparummalaria

Cited by 20 publications

References 69 publications

Pathophysiology and neurologic sequelae of cerebral malaria

Pathophysiology and neurologic sequelae of cerebral malaria

Refining Host-Pathogen Interactions: Organ-on-Chip Side of the Coin

The Glycocalyx and Its Role in Vascular Physiology and Vascular Related Diseases

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