Endothelial cell senescence and thrombosis: Ageing clots.
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.
Center for Cardiology, Cardiology I, University Medical Center Mainz, Germany; Center for Thrombosis and Hemostasis, University Medical Center Mainz, Germany; Deutsches Zentrum für Herz-Kreislaufforschung (DZHK) e.V., Germany.
Magdalena L
ML
Bochenek
Center for Cardiology, Cardiology I, University Medical Center Mainz, Germany.
Eva
E
Schütz
Center for Cardiology, Cardiology I, University Medical Center Mainz, Germany; Deutsches Zentrum für Herz-Kreislaufforschung (DZHK) e.V., Germany. Electronic address: katrin.schaefer@unimedizin-mainz.de.
Katrin
K
Schäfer
D000375:Aging; D000818:Animals; D016922:Cellular Senescence; D004032:Diet; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology*; D006487:Hemostasis; D006801:Humans; D008019:Life Style; D018384:Oxidative Stress; D013927:Thrombosis / Q000097:blood / Q000378:metabolism / Q000473:pathology* / Q000628:therapy
Ageing; Endothelial cells; Senescence; Thrombosis; Vascular biology