The transcription factor cAMP-response element
binding protein (CREB) mediates the
mechanical strain-induced gene expression in
the heart. This study investigated which signaling
pathways are involved in the straininduced
CREB activation using cultured ventricular
fibroblasts from adult rat hearts. CREB
phosphorylation was analyzed by immunocytochemistry
and ELISA. Cyclic mechanical strain
(1 Hz and 5% elongation) for 15 min induced
CREB phosphorylation in all CREB-positive
fibroblasts. Several signaling transduction
pathways can contribute to strain-induced
CREB activation. The inhibition of PKA, PKC,
MEK, p38-MAPK or PI3-kinase partially
reduced the strain-induced CREB phosphorylation.
Activation of PKA by forskolin or PKC by
PMA resulted in a level of CREB phosphorylation
comparable to the reduced level of the
strain-induced CREB phosphorylation in the
presence of PKA or PKC inhibitors. Signaling pathways involving PKC, MEK, p38-MAPK or
PI3-kinase seem to converge during straininduced
CREB activation. PKA interacted additively
with the investigated signaling pathways.
The strain-induced c-Fos expression can
be reduced by PKC inhibition but not by PKA
inhibition. Our results suggest that the complete
strain-induced CREB phosphorylation
involves several signaling pathways that have
a synergistic effect. The influence on gene
expression is dependent on the level and the
time of CREB stimulation. These wide-ranging
possibilities of CREB activation provide a
graduated control system.
Strain, mechanotransduction, cAMP response element binding protein, c-Fos, fibroblasts.
Britta Husse, Department of Physiology, Martin-Luther-University Halle/ Wittenberg, Magdeburger Street 6, D 06097 Halle, Germany. E-mail: email@example.com
Share this Article
Related Content In Cardiovascular Disease
Low-flow, Low-gradient Severe Aortic Stenosis: A Review
Heart International. 2023;17(1):Online ahead of journal publication
The global prevalence of aortic stenosis (AS) has steadily increased over the past several decades.1 In high-income countries, degenerative calcific aortic valve disease is the primary aetiology for AS, whereas chronic rheumatic valve disease and infective endocarditis remain more common causes worldwide.2 Population-wide trends in developed countries suggest a strong relationship between advanced age and incidence of […]
Strategies for Reducing Vascular and Bleeding Risk for Percutaneous Left Ventricular Assist Device-supported High-risk Percutaneous Coronary Intervention
Heart International. 2022;16(2):105–11 DOI: https://doi.org/10.17925/HI.2022.16.2.105
In recent years, patients undergoing non-emergent percutaneous coronary intervention (PCI) procedures have become increasingly older, with a more significant comorbidity burden and complex coronary disease.1 Many of the patients who undergo elective or urgent PCI are surgical turndown patients, for whom PCI is the only revascularization option.2 For these high-risk patients, more interventionalists are opting for […]
Can Percutaneous Coronary Intervention Revive a Failing Heart?
Heart International. 2022;16(2):72–4 DOI: https://doi.org/10.17925/HI.2022.16.2.72
Percutaneous coronary intervention (PCI) has evolved considerably in both technique and technology since Andreas Grüntzig first intervened on a focal, proximal lesion in the left anterior descending artery in 1977.1 While this has resulted in increasingly complex anatomical subsets being treated, contemporary trials of PCI in patients with stable coronary artery disease (CAD) have continued to […]
Journal articles and more to your inbox
Get the latest clinical insights from touchCARDIOSign me up!