2017
DOI: 10.1159/000485284
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Abstract: Background/Aims: Our previous studies demonstrated that intrinsic aortic smooth muscle cell (VSMC) stiffening plays a pivotal role in aortic stiffening in aging and hypertension. However, the underlying molecular mechanisms remain largely unknown. We here hypothesized that Rho kinase (ROCK) acts as a novel mediator that regulates intrinsic VSMC mechanical properties through the serum response factor (SRF) /myocardin pathway and consequently regulates aortic stiffness and blood pressure in hypertension. Methods… Show more

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Cited by 46 publications
(64 citation statements)
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References 43 publications
(66 reference statements)
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“…Treatment with the SRF/myocardin inhibitor CCG‐100602 (CCG) as previously described (Zhou, Lee, Stoll, Ma, Costa, et al 2017; Zhou, Lee, Stoll, Ma, Wiener, et al 2017) had no effect on integrin β1 mRNA relative to vehicle controls in cells from either WKY or SHR aorta (Figure 4a). The abundance of activated integrin β1 protein was markedly attenuated by CCG treatment in VSMCs from SHR TA, but not those from WKY TA (Figure 4b–e).…”
Section: Resultsmentioning
confidence: 89%
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“…Treatment with the SRF/myocardin inhibitor CCG‐100602 (CCG) as previously described (Zhou, Lee, Stoll, Ma, Costa, et al 2017; Zhou, Lee, Stoll, Ma, Wiener, et al 2017) had no effect on integrin β1 mRNA relative to vehicle controls in cells from either WKY or SHR aorta (Figure 4a). The abundance of activated integrin β1 protein was markedly attenuated by CCG treatment in VSMCs from SHR TA, but not those from WKY TA (Figure 4b–e).…”
Section: Resultsmentioning
confidence: 89%
“…Our recent study demonstrated that aortic stiffness reduction preceded the reduction in blood pressure in SHR treated with CCG, suggesting the recovery of aortic elasticity in SHR is not likely an artifact of the reduction in blood pressure, and may even be a contributing factor. (Zhou, Lee, Stoll, Ma, Costa, et al 2017; Zhou, Lee, Stoll, Ma, Wiener, et al 2017). We believe that the mechanisms revealed in the current study may also contribute to aortic stiffness in aging, which allow us insight into the pathological development of hypertension in the elderly.…”
Section: Discussionmentioning
confidence: 99%
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“…Overexpressing SRF by LV-SRF significantly attenuated the antiproliferative and antimigratory effects of miR-125b, suggesting that SRF is a functional downstream target of miR-125b and is involved in the miR-125b-mediated modulation of VSMC function. SRF is a highly conserved and widely expressed single-copy transcription factor that plays extensive role in circulatory system such as cardiac function and hypertension [26,27]. SRF theoretically binds up to 1, 216 permutations of a 10-base pair cis element known as the CArG box [28].…”
Section: Cellular Physiology and Biochemistrymentioning
confidence: 99%