Endothelial cell senescence and thrombosis: Ageing clots
Abstract
Age is an important cardiovascular risk factor. Among others, age is associated with an increased risk to develop thrombotic cardiovascular complications, both in the arterial (acute myocardial infarction, stroke) and the venous (deep vein thrombosis, pulmonary embolism) system, which cannot be explained by the age-associated increase in cardiovascular risk factors alone. A number of studies have demonstrated that the accumulation of senescent endothelial cells and specific phenotypic and functional alterations associated with endothelial cell senescence may play an important role during the development and progression of cardiovascular disease. Prevention of platelet aggregation and thrombosis as well as fibrinolysis are important functions of the endothelium lining the vasculature. Moreover, impaired proliferation and migration of local endothelial cells as well as exhaustion of endogenous endothelial repair mechanisms involving progenitor cells may also contribute to thrombosis and its complications with age by impairing re-endothelialisation. In this short review, we present and discuss important findings regarding the effects of the cardiovascular risk factor age on endothelial cell morphology and function including the senescence-associated secretory phenotype and altered expression of factors involved in thrombosis and fibrinolysis. We also summarize results from clinical and experimental studies in rodent and other models on the possible connection between endothelial senescence and thrombotic events. Furthermore, major mechanisms and pathways underlying endothelial cell senescence and models to study its pathomechanisms are presented. Finally, we briefly discuss potential targets and therapeutic options to prevent, postpone or treat endothelial senescence and thus the increased burden of thrombosis associated with age.
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Microvascular endothelium is a main site of PAI-1 production.
“Microvascular endothelium is a main site of PAI-1 production, and the marked incorporation of PAI-1 in abnormal or persistent clots supports a plausible mechanism that may explain poor clot resolution in COVID-19 (57).”
From Lung epithelial and endothelial damage, loss of tissue repair, inhibition of fibrinolysis, and cellular senescence in fatal COVID-19 (2021) · cites this paper as [57]
Accumulation of senescent endothelial cells leads to cardiovascular thrombotic complications, including arterial and venous thrombotic events.
“Accumulation of senescent endothelial cells leads to cardiovascular thrombotic complications, including arterial (acute myocardial infarction, stroke) and venous (deep vein thrombosis, pulmonary embolism) thrombotic events [52].”
From Immune Clearance of Senescent Cells to Combat Ageing and Chronic Diseases (2020) · cites this paper as [52]
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“Accumulation of senescent endothelial cells leads to cardiovascular thrombotic complications, including arterial (acute myocardial infarction, stroke) and venous (deep vein thrombosis, pulmonary embolism) thrombotic events [52].”
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- Authors
- Bochenek, M. L., Schütz, E., & Schäfer, K.
- Affiliations
- University Medical Center of the Johannes Gutenberg University Mainz (DE)
- Corresponding author
- Schäfer, Katrin
- Venue
- Thrombosis Research
- Publisher
- Elsevier BV
- Published
- 2016-11
- Volume
- 147
- Pages
- 36-45
- ISSN
- 0049-3848 (ISSN-L)
- OpenAlex
- W2523502093
- Cited by
- 96
- References
- 19
- Citations by year
- 2026: 14 · 2025: 14 · 2024: 13 · 2023: 10 · 2022: 13 · 2021: 6 · 2020: 8 · 2019: 8 · 2018: 6 · 2017: 2 · 2016: 2
- FWCI
- 0.71
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Thrombosis Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Keywords
- endothelial cell senescence, thrombosis, aging, senescence-associated secretory phenotype, fibrinolysis, re-endothelialization, endothelial progenitor cells, platelet aggregation, deep vein thrombosis, pulmonary embolism, acute myocardial infarction, stroke, cardiovascular risk factors, therapeutic target
- MeSH terms
- Aging, Animals, Diet, Hemostasis, Humans, Life Style, Thrombosis, Cellular Senescence, Oxidative Stress, Endothelial Cells
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