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Alteration of microvascular mechanotransduction in syrian hamster lacking delta‐sarcoglycan is caused by enhanced oxidative stress
Author(s) -
Bocquet Arnaud,
Chantemèle Eric Belin,
Fromes Yves,
Henrion Daniel,
Loufrani Laurent
Publication year - 2007
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.21.5.a492-c
Subject(s) - mechanotransduction , microbiology and biotechnology , rhoa , biology , medicine , anatomy , chemistry , endocrinology , signal transduction
Myogenic tone (MT) and flow‐mediated‐dilation (FMD) play a key role in resistance arteries. They involve cytoskeletal elements among which dystrophin‐glycoprotein complex (DGC) play a central role. In DCG, delta‐sarcoglycan might play a more critical role in mechanotransduction process. We investigated flow, pressure‐dependant mechanotransduction and signaling pathways of arteries from Syrian myopath hamsters (SMH) lacking delta‐sarcoglycan. Moreover, SMH develop clinic signs of myopathy. Mesenteric resistance arteries (MRA) and aorta were isolated from control or delta‐sarcoglycan deficient hamster and mounted in an arteriogragh to study mechanotransduction, pharmacological reactivity and corresponding signaling pathways. In MRA, MT from delta‐sarcoglycan deficient hamster was reduced by 50% and associated with a RhoA decrease expression. Moreover, FMD was attenuated by 60% and associated with a reduction in eNOS phosphorylation despite a eNOS normal expression. In aorta and MRA, pharmacological reactivity was not modified by the lack of delta‐sarcoglycan except for phenylephrine. Reactive oxygen species was strongly increased in endothelial cells of MRA without variation in smooth muscle cells. DGC integrity is essential for vascular mechanotransduction of pressure and flow in resistance arteries. Thus, this complex plays a specific role in physical forces transduction involved in local blood flow control. As sarcoglycan protein mutation is associated with cardiomyopathy, heart failure associated to specific mutation of delta‐sarcoglycan could be explained in part or aggravated by such vascular defects.