Hypoxia and Inflammation as a Consequence of β-Fibril Accumulation: A Perspective View for New Potential Therapeutic Targets
Amyloidoses are heterogeneous diseases that result from the deposition of toxic insoluble β-sheet fibrillar protein aggregates in different tissues. The cascade of molecular events leading to amyloidoses and to the related clinical manifestations is not completely understood. Nevertheless, it is kno...
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doaj-d3ef710963e4479081e318029694709e2020-11-24T21:37:14ZengHindawi LimitedOxidative Medicine and Cellular Longevity1942-09001942-09942019-01-01201910.1155/2019/79353107935310Hypoxia and Inflammation as a Consequence of β-Fibril Accumulation: A Perspective View for New Potential Therapeutic TargetsMatteo A. Russo0Carlo Tomino1Enza Vernucci2Federica Limana3Luigi Sansone4Andrea Frustaci5Marco Tafani6MEBIC Consortium, San Raffaele Rome Open University, Via val Cannuta 247, 00166 Rome, ItalyIRCCS San Raffaele, Scientific Direction, Via Val Cannuta 247, 00166 Rome, ItalyMEBIC Consortium, San Raffaele Rome Open University, Via val Cannuta 247, 00166 Rome, ItalyMEBIC Consortium, San Raffaele Rome Open University, Via val Cannuta 247, 00166 Rome, ItalyMEBIC Consortium, San Raffaele Rome Open University, Via val Cannuta 247, 00166 Rome, ItalyDepartment of Cardiovascular, Nephrologic, Anesthesiologic and Geriatric Sciences, Sapienza University of Rome, Viale Regina Elena 324, 00161 Rome, ItalyDepartment of Experimental Medicine, Sapienza University of Rome, Viale Regina Elena 324, 00161 Rome, ItalyAmyloidoses are heterogeneous diseases that result from the deposition of toxic insoluble β-sheet fibrillar protein aggregates in different tissues. The cascade of molecular events leading to amyloidoses and to the related clinical manifestations is not completely understood. Nevertheless, it is known that tissue damage associated to this disease involves alteration of tissue architecture, interaction with cell surface receptors, inflammation elicited by the amyloid protein deposition, oxidative stress, and apoptosis. However, another important aspect to consider is that systemic protein massive deposition not only subverts tissue architecture but also determines a progressive cellular hypertrophy and dilation of the extracellular space enlarging the volume of the organ. Such an alteration increases the distance between cells and vessels with a drop in pO2 that, in turn, causes both necrotic cell death and activation of the hypoxia transcription factor HIF-1α. Herewith, we propose the hypothesis that both cell death and hypoxia represent two important events for the pathogenesis of damage and progression of amyloidoses. In fact, molecules released by necrotic cells activate inflammatory cells from one side while binding to HIF-1α-dependent membrane receptors expressed on hypoxic parenchymal cells on the other side. This latter event generates a signaling cascade triggering NFκB activation and chronic inflammation. Finally, we also suggest that this scenario, once proved and detailed, might suggest important targets for new therapeutic interventions.http://dx.doi.org/10.1155/2019/7935310 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Matteo A. Russo Carlo Tomino Enza Vernucci Federica Limana Luigi Sansone Andrea Frustaci Marco Tafani |
spellingShingle |
Matteo A. Russo Carlo Tomino Enza Vernucci Federica Limana Luigi Sansone Andrea Frustaci Marco Tafani Hypoxia and Inflammation as a Consequence of β-Fibril Accumulation: A Perspective View for New Potential Therapeutic Targets Oxidative Medicine and Cellular Longevity |
author_facet |
Matteo A. Russo Carlo Tomino Enza Vernucci Federica Limana Luigi Sansone Andrea Frustaci Marco Tafani |
author_sort |
Matteo A. Russo |
title |
Hypoxia and Inflammation as a Consequence of β-Fibril Accumulation: A Perspective View for New Potential Therapeutic Targets |
title_short |
Hypoxia and Inflammation as a Consequence of β-Fibril Accumulation: A Perspective View for New Potential Therapeutic Targets |
title_full |
Hypoxia and Inflammation as a Consequence of β-Fibril Accumulation: A Perspective View for New Potential Therapeutic Targets |
title_fullStr |
Hypoxia and Inflammation as a Consequence of β-Fibril Accumulation: A Perspective View for New Potential Therapeutic Targets |
title_full_unstemmed |
Hypoxia and Inflammation as a Consequence of β-Fibril Accumulation: A Perspective View for New Potential Therapeutic Targets |
title_sort |
hypoxia and inflammation as a consequence of β-fibril accumulation: a perspective view for new potential therapeutic targets |
publisher |
Hindawi Limited |
series |
Oxidative Medicine and Cellular Longevity |
issn |
1942-0900 1942-0994 |
publishDate |
2019-01-01 |
description |
Amyloidoses are heterogeneous diseases that result from the deposition of toxic insoluble β-sheet fibrillar protein aggregates in different tissues. The cascade of molecular events leading to amyloidoses and to the related clinical manifestations is not completely understood. Nevertheless, it is known that tissue damage associated to this disease involves alteration of tissue architecture, interaction with cell surface receptors, inflammation elicited by the amyloid protein deposition, oxidative stress, and apoptosis. However, another important aspect to consider is that systemic protein massive deposition not only subverts tissue architecture but also determines a progressive cellular hypertrophy and dilation of the extracellular space enlarging the volume of the organ. Such an alteration increases the distance between cells and vessels with a drop in pO2 that, in turn, causes both necrotic cell death and activation of the hypoxia transcription factor HIF-1α. Herewith, we propose the hypothesis that both cell death and hypoxia represent two important events for the pathogenesis of damage and progression of amyloidoses. In fact, molecules released by necrotic cells activate inflammatory cells from one side while binding to HIF-1α-dependent membrane receptors expressed on hypoxic parenchymal cells on the other side. This latter event generates a signaling cascade triggering NFκB activation and chronic inflammation. Finally, we also suggest that this scenario, once proved and detailed, might suggest important targets for new therapeutic interventions. |
url |
http://dx.doi.org/10.1155/2019/7935310 |
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