Molecular pathways of endothelial cell activation for (targeted) pharmacological intervention of chronic inflammatory diseases

Joanna M. Kułdo, Ken Ichi Ogawara, Naomi Werner, Sigridur A. Ásgeirsdóttir, Jan A.A.M. Kamps, Robbert J. Kok, Grietje Molema

Research output: Contribution to journalReview article

71 Citations (Scopus)

Abstract

In chronic inflammatory conditions, endothelial cells actively recruit immune cells from the circulation into the underlying tissue and participate in angiogenesis to support the continuous demand for oxygen and nutrients. They do so in response to activation by cytokines and growth factors such as tumour necrosis factor α (TNFα), interleukin-1 (IL-1), vascular endothelial growth factor (VEGF), and fibroblast growth factors (FGFs). Receptor triggering initiates intracellular signal transduction leading to activation of nuclear factor κB (NFκB), mitogen activated protein kinase (MAPK) activity, and nitric oxide and reactive oxygen species production, among others. As a result, adhesion molecules, cytokines and chemokines, and a variety of other genes are being expressed that mediate and control the inflammatory process. In recent years, different classes of drugs have been developed that interfere with selected enzymes involved in the intracellular signalling cascades. In endothelial cell cultures, they exert potent inhibitory effects on the expression of genes, while several studies also report on in vivo effectiveness to confine the inflammatory responses. To prevent undesired toxicity and to improve drug behaviour and efficacy, drug carrier systems have been developed that selectively deliver the therapeutics into the activated endothelial cells. The above subjects are recapitulated to give an overview on the status of development of endothelial cell directed therapeutic strategies to pharmacologically interfere with chronic inflammatory diseases.

Original languageEnglish
Pages (from-to)11-39
Number of pages29
JournalCurrent Vascular Pharmacology
Volume3
Issue number1
DOIs
Publication statusPublished - Jan 1 2005

Keywords

  • Angiogenesis
  • Chronic inflammation
  • Drugs
  • Endothelial cells
  • Pharmacology
  • Signal transduction
  • Vascular drug targeting

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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  • Cite this

    Kułdo, J. M., Ogawara, K. I., Werner, N., Ásgeirsdóttir, S. A., Kamps, J. A. A. M., Kok, R. J., & Molema, G. (2005). Molecular pathways of endothelial cell activation for (targeted) pharmacological intervention of chronic inflammatory diseases. Current Vascular Pharmacology, 3(1), 11-39. https://doi.org/10.2174/1570161052773898