doi: 10.1161/CIRCRESAHA.107.170548
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© 2008 American Heart Association, Inc.
Editorials |
Another TRP to Endothelial Dysfunction
TRPM2 and Endothelial Permeability
From the Institute of Pharmacology and Toxicology, Philipps-University of Marburg, Germany.
Correspondence to Alexander Dietrich, PhD, Institute of Pharmacology and Toxicology, Philipps-University of Marburg, Karl-von-Frisch-Strasse 1, 35043 Marburg, Germany. E-mail dietrica@staff.uni-marburg.de
See related article, pages 347–355
Key Words: TRPM2 • H2O2-induced Ca2+ influx • reactive oxygen species • oxidative stress • endothelial permeability
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
The vascular endothelium acts not only as a passive barrier between plasma and extracellular fluid but is intimately involved in various physiological processes including the regulation of systemic and regional vascular tone, blood coagulation, cell–cell adhesion, wound healing, cellular proliferation, and angiogenesis. The implications of endothelial dysfunction in many pathological states have rendered modulation of endothelial functions as a promising therapeutic strategy for cardiovascular and cerebrovascular disease. Increasing endothelial permeability by oxidative stress through the production of oxygen metabolites is an important trigger for endothelial dysfunction.
Until now, the general belief was that the resulting reactive oxygen species would directly damage the endothelium.1 The study by Hecquet et al in this issue of Circulation Research identified transient receptor potential melastatin (TRPM)2 as a nonselective cation channel inducing increases in the cytosolic Ca2+ concentration ([Ca 2+]i) in primary cultured human pulmonary artery endothelial cells in response to reactive oxygen species (Figure).2 Endothelial cells are generally viewed as electrically nonexcitable, lacking functional voltage-gated Ca2+ channels. A major mode of Ca2+ entry in these cells in response to both chemical and mechanical stimuli is the so-called nonselective cation entry through TRP channels.3 Several members of the TRP superfamily have been identified and characterized in the endothelium to date: the classic TRP channels TRPC1, -3, -4, and -6; TRPP1 and -2 of the P family; TRPV1, -2, and -4 representing the V family; as well as the melastatin-related TRPM2, -4, and -7. Whereas TRPC1, -C4, -C6, and -M7 have been linked
Related Article:
Circ. Res. 2008 102: 347-355.