Modulation of protein kinase activity and gene expression by reactive oxygen species and their role in vascular physiology and pathophysiology

Kathy K. Griendling, Dan Sorescu, Bernard Lassègue, Masuko Fukai

Research output: Contribution to journalReview article

759 Citations (Scopus)

Abstract

Emerging evidence indicates that reactive oxygen species, especially superoxide and hydrogen peroxide, are important signaling molecules in cardiovascular cells. Their production is regulated by hormone-sensitive enzymes such as the vascular NAD(P)H oxidases, and their metabolism is coordinated by antioxidant enzymes such as superoxide dismutase, catalase, and glutathione peroxidase. Both of these reactive oxygen species serve as second messengers to activate multiple intracellular proteins and enzymes, including the epidermal growth factor receptor, c-Src, p38 mitogen-activated protein kinase, Ras, and Akt/protein kinase B. Activation of these signaling cascades and redox-sensitive transcription factors leads to induction of many genes with important functional roles in the physiology and pathophysiology of vascular cells. Thus, reactive oxygen species participate in vascular smooth muscle cell growth and migration; modulation of endothelial function, including endothelium-dependent relaxation and expression of a proinflammatory phenotype; and modification of the extracellular matrix. All of these events play important roles in vascular diseases such as hypertension and atherosclerosis, suggesting that the sources of reactive oxygen species and the signaling pathways that they modify may represent important therapeutic targets.

Original languageEnglish (US)
Pages (from-to)2175-2183
Number of pages9
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume20
Issue number10
DOIs
StatePublished - Jan 1 2000
Externally publishedYes

Fingerprint

Protein Kinases
Blood Vessels
Reactive Oxygen Species
Gene Expression
Enzymes
ras Proteins
Proto-Oncogene Proteins c-akt
NADPH Oxidase
Second Messenger Systems
p38 Mitogen-Activated Protein Kinases
Glutathione Peroxidase
Vascular Diseases
Vascular Smooth Muscle
Epidermal Growth Factor Receptor
Superoxides
Catalase
Hydrogen Peroxide
Superoxide Dismutase
Oxidation-Reduction
Smooth Muscle Myocytes

Keywords

  • Atherosclerosis
  • Endothelial cells
  • Hypertension
  • Reactive oxygen species
  • Vascular smooth muscle

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Modulation of protein kinase activity and gene expression by reactive oxygen species and their role in vascular physiology and pathophysiology. / Griendling, Kathy K.; Sorescu, Dan; Lassègue, Bernard; Fukai, Masuko.

In: Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 20, No. 10, 01.01.2000, p. 2175-2183.

Research output: Contribution to journalReview article

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