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

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Health and Cognition in Old Age

Part of the book series: International Perspectives on Aging ((Int. Perspect. Aging,volume 10))

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Abstract

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.

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Acknowledgments

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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Authors and Affiliations

  1. Department of Nephrology, Hannover Medical School, Hannover, Germany

    Yulia Kiyan, Hermann Haller & Inna Dumler

  2. The Lipid Research Laboratory, Technion Faculty of Medicine and Rambam Medical Center, Haifa, Israel

    Bianca Fuhrman

Authors
  1. Yulia Kiyan
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  2. Bianca Fuhrman
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  3. Hermann Haller
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  4. Inna Dumler
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Corresponding author

Correspondence to Yulia Kiyan .

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Editors and Affiliations

  1. Faculty of Language and Literature, Humanities, Arts and Education, University of Luxembourg, Walferdange, Luxembourg

    Anja K. Leist

  2. Gerontology Research Center, University of Jyväskylä, Jyväskylä, Finland

    Jenni Kulmala

  3. Mental Health Promotion Unit, National Institute for Health and Welfare, THL, Vaasa, Finland

    Fredrica Nyqvist

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© 2014 Springer International Publishing Switzerland

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Kiyan, Y., Fuhrman, B., Haller, H., Dumler, I. (2014). Vascular Aging: Revealing the Role and Clinical Perspectives of the Urokinase System. In: Leist, A., Kulmala, J., Nyqvist, F. (eds) Health and Cognition in Old Age. International Perspectives on Aging, vol 10. Springer, Cham. https://doi.org/10.1007/978-3-319-06650-9_2

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