The cAMP response element-binding protein (CREB) is a transcription factor that mediates the cellular response to metabolic and mitogenic signals. Whether CREB contributes to vascular function has received little attention, especially in relation to the processes associated with atherosclerotic disease progression and restenosis. This study examined the involvement of CREB in the mitogenic actions of angiotensin II (AngII), a growth factor that promotes neointimal hyperplasia in response to vascular injury. Treatments were performed on quiescent vascular smooth muscle cells (VSMCs) obtained from a porcine explant model. Organ culture was performed on porcine hearts subjected to angioplasty ex vivo. Stimulation of VSMCs with AngII resulted in transient CREB phosphorylation. Proliferation of smooth muscle cells in response to AngII was reduced by 90 % after infection with adenovirus expressing dominant-negative killer CREB (kCREB) mutant. Likewise, expression of kCREB prevented angioplasty-induced neointimal hyperplasia. AngII-induced CREB phosphorylation was independent of cAMP activation. Examination of putative CREB kinases revealed that MSK was responsible for phosphorylating CREB. In addition, inhibition of PKC revealed that this kinase operates upstream and activates MSK. These results indicate that activation of CREB via PKC and MSK is essential for SMC proliferation in response to AngII.

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Background Development of instruments capable of detecting early stage vascular disease has increased interest in employing arterial stiffness (e.g. pulse wave velocity (PWV), augmentation index (AIx)) and endothelial dysfunction (e.g. reactive hyperemia index (RHI)) to diagnose atherosclerotic disease before occurrence of a cardiovascular event. However, amongst the equipment designed for this purpose, there is insufficient information regarding each of these parameters to establish appropriate cutoffs to distinguish between healthy and unhealthy blood vessels. To address these limitations, the study was designed to establish the upper arterial stiffness and endothelial function thresholds in a healthy population, by comparing the outputs from different instruments capable of measuring PWV, AIx and RHI. Methods A systematic comparison of PWV, AIx and RHI was conducted to determine the inter-relationships between these parameters of vascular functionality. Outputs were obtained non-invasively using three instruments, the VP-1000 (VP), SphygmoCor (SC), and EndoPAT (EP), in 40 apparently healthy males and females. Results Correlations were found between the brachial-ankle PWV and radial-ankle PWV (by VP and SC), and PWV (VP) with AIx (SC). The interchangeability of these outputs was demonstrated by the Bland Altman test, making it feasible to extrapolate cut-offs for radial-ankle PWV and AIx equivalent to brachial-ankle PWV that signify healthy vessels. In contrast, RHI showed no association with AIx, suggesting these endothelial and arterial parameters are functionally distinct. Conclusions It was concluded that it is possible to compare the vascular function outputs of different instruments and identify healthy from unhealthy vessels, even though the approaches for quantifying the underlying physiological processes may differ. In this way, non-invasive determination of arterial function could be a new paradigm for detecting existing early stage asymptomatic atherosclerotic disease in individuals using techniques that are amenable to the clinical setting. Electronic supplementary material The online version of this article (10.1186/s12872-019-1167-3) contains supplementary material, which is available to authorized users.