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Transcapillary exchange: role and importance of the interstitial fluid pressure and the extracellular matrix
Abstract
This review will summarize current knowledge on the role of the extracellular matrix (ECM) in general and on the interstitial fluid pressure (P(if)) in particular with regard to their importance in transcapillary exchange. The fluid volume in the interstitial space is normally regulated within narrow limits by automatic re-adjustment of the interstitial hydrostatic and colloid osmotic pressures in response to perturbations in capillary filtration and by the lymphatics. Contrary to this commonly accepted view, P(if) can become an active force and create a fluid flux across the capillaries in several inflammatory reactions and trauma situations rather than limit the changes occurring. The molecular mechanisms involved in the lowering of P(if) include the release of cellular tension exerted on the collagen and microfibril networks in the connective tissue via the collagen-binding beta(1)-integrins, thereby allowing the glycosaminoglycan ground substance, which is normally underhydrated, to expand and take up fluid. Several growth factors and cytokines, including the platelet-derived growth factor BB, are able to reverse a lowering of P(if) and restore the normal compaction of the ECM. The magnitude of the lowering of P(if) varies with the inflammatory response. In several inflammatory reactions, a lowering of P(if) to -5 to -10 mmHg is seen, which will increase capillary filtration by 10-20 times since the normal capillary filtration pressure is usually 0.5-1 mmHg (skin and skeletal muscle). Unless this lowering of P(if) is taken into account, the enhanced solute flux resulting from an inflammatory response will be ascribed to an increased capillary permeability.
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“This elevated IFP diminishes convective transport, reduces vascular perfusion, and severely impairs drug accumulation in the tumor core [88,89].”
From Modeling Tumor Microenvironment Complexity In Vitro: Spheroids as Physiologically Relevant Tumor Models and Strategies for Their Analysis (2025) · cites this paper as [88]
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Lorente, J. V., Hahn, R. G., Jover, J. M., Cojo, E. D., Hervías, M., Jiménez, I., Uña, R., Clau-Terré, F., García, M. I. M., Llau, J. V., et al. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12185930 · Cited by 11
Cui, M., Dong, H., Duan, W., Wang, X., Liu, Y., Shi, L., & Zhang, B. (2024) · PeerJ · doi:10.7717/peerj.16958 · Cited by 11
Metadata
- Authors
- Reed, R. K., & Rubin, K.
- Affiliations
- University of Bergen (NO)
- Uppsala University (SE)
- Corresponding author
- Reed, Rolf K.
- Venue
- Cardiovascular Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2010-05-13
- Volume
- 87
- Issue
- 2
- Pages
- 211-217
- ISSN
- 0008-6363 (ISSN-L)
- 1755-3245
- OpenAlex
- W2153147895
- Cited by
- 209
- References
- 61
- Citations by year
- 2026: 16 · 2025: 21 · 2024: 13 · 2023: 16 · 2022: 12 · 2021: 16 · 2020: 11 · 2019: 12 · 2018: 10 · 2017: 9 · 2016: 7 · 2015: 10 · 2014: 13 · 2013: 14 · 2012: 12
- FWCI
- 1.23
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cardiovascular Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Swedish Cancer Foundation
- Vetenskapsrådet
- Norges Forskningsråd
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Health Sciences › Medicine › Oncology › Lymphatic System and Diseases
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Keywords
- transcapillary exchange, interstitial fluid pressure, extracellular matrix, capillary filtration, lymphatic vessels, inflammation, trauma (physical injury), beta1 integrin, collagen, microfibrils, glycosaminoglycans, PDGF-BB, capillary permeability, colloid osmotic pressure, interstitial hydrostatic pressure
- MeSH terms
- Animals, Body Fluids, Capillaries, Capillary Permeability, Cytoskeleton, Edema, Endothelium, Vascular, Extracellular Matrix, Homeostasis, Humans, Hydrostatic Pressure, Inflammation, Models, Cardiovascular, Osmotic Pressure, Signal Transduction, Inflammation Mediators, Integrin beta1, Integrin alpha2beta1, Extracellular Fluid
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