Vascular Aging: Revealing the Role and Clinical Perspectives of the Urokinase System

  • Yulia KiyanEmail author
  • Bianca Fuhrman
  • Hermann Haller
  • Inna Dumler
Part of the International Perspectives on Aging book series (Int. Perspect. Aging, volume 10)


Cardiovascular diseases (CVD) are the most common cause of death among the elderly population in Western countries. Despite progress in managing some of the established risk factors like hypertension and hypercholesterolemia, the incidence of CVD is predicted to increase as the population ages. The aging process itself is associated with morphological and functional changes in the vasculature. Moreover, age-related changes render the cardiovascular system susceptible to damaging actions of risk factors and diseases. Vascular smooth muscle cells (VSMCs) are intrinsically involved in age-associated changes of the vasculature. With age, the VSMC phenotype shifts towards a pathophysiological synthetic phenotype characterized by migration, proliferation, release of inflammatory cytokines, and augmented extracellular matrix deposition. The molecular mechanisms underlying age-associated VSMC phenotypic changes remain unclear. Recent large-scale population studies showed a close correlation between the urokinase/urokinase receptor system and CVD, inflammation, aging, and mortality. In our research, we have identified a new link between the urokinase system and arterial wall changes during vascular remodeling and initiation/progression of atherosclerosis. The urokinase system exerts its function at different levels. Systemically, it modulates oxidative stress via regulation of paraoxonase 1 production by the liver. Locally in the blood vessel wall, the urokinase system modulates VSMCs towards the synthetic phenotype via proteasomal degradation of the transcription coactivator, myocardin. Furthermore, the urokinase system interferes with VSMC senescence that influences the outcome of vascular remodeling and the fate of atherosclerotic plaques. The variety of functions exerted by the urokinase system in the vascular wall makes it an attractive therapeutic target.


Vascular Remodel Proteasomal Degradation Serum Response Factor Contractile Phenotype VSMC Proliferation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



We would like to thank Dr. K. Grote for his comments on an earlier draft of the manuscript. This work was supported by an ERA-AGE FLARE grant, financed by Bundesministerium für Bildung und Forschung [01 ET 0802]; grant P59/10//A101/10 from Else Kroener-Fresenius-Stiftung; grants from the Deutsche Forschungsgemeinschaft [KI 1376/2-1 and KI 1367/2-2; DU 344/7-1] and from the Deutscher Akademischer Austausch Dienst [A/08/98019]; and Israel Science Foundation Grant 669/09, funded by the Israel Academy of Sciences and Humanities.


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Copyright information

© Springer International Publishing Switzerland 2014

Authors and Affiliations

  • Yulia Kiyan
    • 1
    Email author
  • Bianca Fuhrman
    • 2
  • Hermann Haller
    • 1
  • Inna Dumler
    • 1
  1. 1.Department of NephrologyHannover Medical SchoolHannoverGermany
  2. 2.The Lipid Research LaboratoryTechnion Faculty of Medicine and Rambam Medical CenterHaifaIsrael

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