Metformin attenuates adhesion between cancer and endothelial cells in chronic hyperglycemia by recovery of the endothelial glycocalyx barrier

Targosz‐Korecka, Marta; Malek-Zietek, Katarzyna E.; Klóska, Damian; Rajfur, Zenon; Stępień, Ewa; Grochot-Przęczek, Anna; Szymoński, Marek

doi:10.1016/j.bbagen.2020.129533

Cited by 25 publications

(25 citation statements)

References 51 publications

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“…Metformin might be a promising drug for protection and regeneration of eGC. Experimental studies have shown metformin-induced recovery of endothelial glycocalyx length and density and the resulting attenuation of adhesive interactions between the endothelium and cancer cells, which might be caused by metformin impact on the nanomechanical and adhesive properties of endothelial and cancer cells in chronic hyperglycemia [110]. Previously reported cardiovascular benefits of metformin may also improve the endothelial glycocalyx.…”

Section: Metforminmentioning

confidence: 99%

Can Endothelial Glycocalyx Be A Major Morphological Substrate in Pre-Eclampsia?

Ziganshina

Yarotskaya

Bovin

et al. 2020

IJMS

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Today pre-eclampsia (PE) is considered as a disease of various theories; still all of them agree that endothelial dysfunction is the leading pathogenic factor. Endothelial dysfunction is a sequence of permanent immune activation, resulting in the change of both the phenotype and the functions of an endothelial cell and of the extracellular layer associated with the cell membrane—endothelial glycocalyx (eGC). Numerous studies demonstrate that eGC mediates and regulates the key functions of endothelial cells including regulation of vascular tone and thromboresistance; and these functions are disrupted during PE. Taking into account that eGC and its components undergo alterations under pathological conditions leading to endothelial activation, it is supposed that eGC plays a certain role in pathogenesis of PE. Envisaging the eGC damage as a key factor of PE, might be a new approach to prevention, treatment, and rehabilitation of patients with PE. This approach could include the development of drugs protecting eGC and promoting regeneration of this structure. Since the issue of PE is far from being solved, any effort in this direction might be valuable.

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Section: Metforminmentioning

confidence: 99%

Can Endothelial Glycocalyx Be A Major Morphological Substrate in Pre-Eclampsia?

Ziganshina

Yarotskaya

Bovin

et al. 2020

IJMS

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“…Metformin, another potential neurorestorative therapy, has also been shown to induce recovery of memory and learning by increasing the expression of the neutrophin BDNF (Ghadernezhad et al, 2016). Interestingly, metformin has also been shown to regenerate the GCX (Eskens et al, 2013;Targosz-Korecka et al, 2020). However, whether or not metformin-induced GCX regeneration plays a role in neurorestoration following stroke has not been studied.…”

Section: Neurorestorationmentioning

confidence: 99%

Blood-Brain Barrier Damage in Ischemic Stroke and Its Regulation by Endothelial Mechanotransduction

et al. 2020

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Ischemic stroke, a major cause of mortality in the United States, often contributes to disruption of the blood-brain barrier (BBB). The BBB along with its supportive cells, collectively referred to as the “neurovascular unit,” is the brain’s multicellular microvasculature that bi-directionally regulates the transport of blood, ions, oxygen, and cells from the circulation into the brain. It is thus vital for the maintenance of central nervous system homeostasis. BBB disruption, which is associated with the altered expression of tight junction proteins and BBB transporters, is believed to exacerbate brain injury caused by ischemic stroke and limits the therapeutic potential of current clinical therapies, such as recombinant tissue plasminogen activator. Accumulating evidence suggests that endothelial mechanobiology, the conversion of mechanical forces into biochemical signals, helps regulate function of the peripheral vasculature and may similarly maintain BBB integrity. For example, the endothelial glycocalyx (GCX), a glycoprotein-proteoglycan layer extending into the lumen of bloods vessel, is abundantly expressed on endothelial cells of the BBB and has been shown to regulate BBB permeability. In this review, we will focus on our understanding of the mechanisms underlying BBB damage after ischemic stroke, highlighting current and potential future novel pharmacological strategies for BBB protection and recovery. Finally, we will address the current knowledge of endothelial mechanotransduction in BBB maintenance, specifically focusing on a potential role of the endothelial GCX.

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“…Adhesive interactions in biological systems can be monitored using the force spectroscopy method with an atomic force microscope (AFM). For many years, AFM based force-spectroscopy has been used to monitor the interactions between individual cells (single-cell force spectroscopy, SCFS) 40 , 41 or to study the bonds between individual molecules (single-molecule force spectroscopy SMFS) 42 . Moreover, very recently, it was demonstrated that single-molecule AFM force spectroscopy could be used to investigate molecular interaction and inhibition of SARS-CoV-2 binding to the ACE2 receptor for A549 cells 43 .…”

Section: Introductionmentioning

confidence: 99%

Endothelial glycocalyx shields the interaction of SARS-CoV-2 spike protein with ACE2 receptors

Targosz‐Korecka

Kubisiak

Klóska

et al. 2021

Sci Rep

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Endothelial cells (ECs) play a crucial role in the development and propagation of the severe COVID-19 stage as well as multiorgan dysfunction. It remains, however, controversial whether COVID-19-induced endothelial injury is caused directly by the infection of ECs with SARS-CoV-2 or via indirect mechanisms. One of the major concerns is raised by the contradictory data supporting or denying the presence of ACE2, the SARS-CoV-2 binding receptor, on the EC surface. Here, we show that primary human pulmonary artery ECs possess ACE2 capable of interaction with the viral Spike protein (S-protein) and demonstrate the crucial role of the endothelial glycocalyx in the regulation of the S-protein binding to ACE2 on ECs. Using force spectroscopy method, we directly measured ACE2- and glycocalyx-dependent adhesive forces between S-protein and ECs and characterized the nanomechanical parameters of the cells exposed to S-protein. We revealed that the intact glycocalyx strongly binds S-protein but screens its interaction with ACE2. Reduction of glycocalyx layer exposes ACE2 receptors and promotes their interaction with S-protein. These results indicate that the susceptibility of ECs to COVID-19 infection may depend on the glycocalyx condition.

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Metformin attenuates adhesion between cancer and endothelial cells in chronic hyperglycemia by recovery of the endothelial glycocalyx barrier

Cited by 25 publications

References 51 publications

Can Endothelial Glycocalyx Be A Major Morphological Substrate in Pre-Eclampsia?

Can Endothelial Glycocalyx Be A Major Morphological Substrate in Pre-Eclampsia?

Blood-Brain Barrier Damage in Ischemic Stroke and Its Regulation by Endothelial Mechanotransduction

Endothelial glycocalyx shields the interaction of SARS-CoV-2 spike protein with ACE2 receptors

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