HPDA/Zn as a CREB Inhibitor for Ultrasound Imaging and Stabilization of Atherosclerosis Plaque^†

Thrombosis, secondary to rupture of unstable plaque, is a fatal risk factor for myocardial infarction and ischemic stroke. At present, more novel methods are needed for the diagnosis and treatment of vulnerable plaque. Here, we report a hollow polydopamine/Zn (HPDA/Zn) ultrasound contrast agent. Through western-blot, Elisa, and other experiments, we found that in addition to having a good contrast-enhancement capability in ultrasound imaging in vitro and in vivo, HPDA/Zn also has the effect of reducing the expression of CREB. CREB protein and its downstream-regulated proteins and factors are closely related to the stability of plaque. HPDA/Zn has the effect of reducing the expression of CREB protein, which leads to the decrease of expression of MMP-9, the regulatory protein downstream of the CREB protein. In addition, it also reduces the secretion of inflammatory factors hs-CRP and IL-17A. Thus, HPDA/Zn can stabilize plaque by inhibiting CREB and reducing plaque vulnerable markers and inflammatory factors. In a word, HPDA/Zn is a kind of ultrasound contrast agent, which can stabilize plaques by inhibiting CREB protein.