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Increased fibrinogen content induces release of endothelin‐1 from endothelial cells
Author(s) -
Sen Utpal,
Tyagi Neetu,
Moshal Karni S.,
Dean William L.,
Roberts Andrew M.,
Tyagi Suresh C.,
Lominadze David
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.732.12
Subject(s) - vasoconstriction , extracellular , chemistry , endothelin 1 , in vivo , mapk/erk pathway , kinase , fibrinogen , endothelin receptor , endocrinology , protein kinase c , vasodilation , medicine , pharmacology , microbiology and biotechnology , biochemistry , biology , receptor
We previously showed that fibrinogen (Fg) increases microvascular constriction in vivo . In the present study we tested the hypothesis that Fg could cause vasoconstriction by affecting release and formation of endothlin‐1 (ET‐1) from vascular endothelial cells (EC). Fg‐induced formation of ET‐1 was studied using rat cardiac microvascular ECs. Confluent ECs were given one of the following treatments: Fg (2 or 4 mg/ml), Fg (4 mg/ml) with extracellular signal‐regulated kinase (ERK) kinase inhibitors (PD98059, or U0126), Fg (4 mg/ml) with an antibody against intercellular adhesion molecule‐1 (ICAM‐1), or medium alone for 45 min. The amount of formed ET‐1 in the cell growth medium was measured by ELISA. Fg caused a dose‐dependent increase in ET‐1 production from ECs. Fg‐induced ET‐1 production was inhibited by ERK kinase inhibitors and by the antibody to ICAM‐1. These data suggest that Fg‐induced vasoconstriction may be mediated through increased release and formation of ET‐1. This mechanism may help to explain a role of Fg in contributing to increased microvascular constriction during diseases such as hypertension, stroke, and diabetes that are accompanied by an increased blood content of Fg. Supported by NIH grant# HL080394 to DL.