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Capitalizing on diversity: an integrative approach towards the multiplicity of cellular mechanisms underlying myogenic responsiveness.

Abstract：

:The intrinsic ability of resistance arteries to respond to transmural pressure is the single most important determinant of their function. Despite an ever-growing catalogue of signalling pathways that underlie the myogenic response, it remains an enigmatic mechanism. The myogenic response's mechanistic diversity has largely been attributed to 'hard-wired' differences across species and vascular beds; however, emerging evidence suggests that the mechanistic basis for the myogenic mechanism is, in fact, 'plastic'. This means that the myogenic response can change quantitatively (i.e. change in magnitude) and qualitatively (i.e. change in mechanistic basis) in response to environmental challenges (e.g. disease conditions). Consequently, understanding the dynamics of how the myogenic response capitalizes on its mechanistic diversity is key to unlocking clinically viable interventions. Using myogenic sphingosine-1-phosphate (S1P) signalling as an example, this review illustrates the remarkable plasticity of the myogenic response. We propose that currently unidentified 'organizational programmes' dictate the contribution of individual signalling pathways to the myogenic response and introduce the concept that certain signalling elements act as 'divergence points' (i.e. as the potential higher level regulatory sites). In the context of pressure-induced S1P signalling, the S1P-generating enzyme sphingosine kinase 1 serves as a divergence point, by orchestrating the calcium-dependent and -independent signalling pathways underlying microvascular myogenic responsiveness. By acting on divergence points, the proposed 'organizational programmes' could form the basis for the flexible recruitment and fine-tuning of separate signalling streams that underlie adaptive changes to the myogenic response and its distinctiveness across species and vascular beds.

journal_name

Cardiovasc Res

journal_title

Cardiovascular research

authors

Lidington D,Schubert R,Bolz SS

doi

10.1093/cvr/cvs345

subject

Has Abstract

pub_date

2013-03-01 00:00:00

pages

404-12

issue

eissn

0008-6363

issn

1755-3245

pii

cvs345

journal_volume

pub_type

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Capitalizing on diversity: an integrative approach towards the multiplicity of cellular mechanisms underlying myogenic responsiveness.