Department of Aortic Surgery, Fuwai Central China Cardiovascular Hospital, Henan, China; Department of Vascular and Endovascular Surgery, Henan Provincial People's Hospital, Henan, China; Cardiovascular Surgery Laboratory, Renmin Hospital of Wuhan University, Wuhan, China.
Hubei Clinic Research Center for Assisted Reproductive Technology and Embryonic Development, Wuhan, China; Reproductive Medical Center, Renmin Hospital of Wuhan University, Wuhan, China.
Biochim Biophys Acta Mol Basis Dis. 2023 Jun;1869(5):166667. doi: 10.1016/j.bbadis.2023.166667. Epub 2023 Mar 9.
Recent studies validated the expression of extraoral bitter taste receptors and established the importance of regulatory functions that are associated with various cellular biological processes of these receptors. However, the importance of bitter taste receptors' activity in neointimal hyperplasia has not yet been recognized. The bitter taste receptors activator amarogentin (AMA) is known to regulate a variety of cellular signals, including AMP-activated protein kinase (AMPK), STAT3, Akt, ERK, and p53, which are associated with neointimal hyperplasia.
The present study assessed the effects of AMA on neointimal hyperplasia and explored the potential underlying mechanisms.
No cytotoxic concentration of AMA significantly inhibited the proliferation and migration of VSMCs induced by serum (15 % FBS) and PDGF-BB. In addition, AMA significantly inhibited neointimal hyperplasia of the cultured great saphenous vein in vitro and ligated mouse left carotid arteries in vivo, while the inhibitory effect of AMA on the proliferation and migration of VSMCs was mediated via the activation of AMPK-dependent signaling, which could be blocked via AMPK inhibition.
The present study revealed that AMA inhibited the proliferation and migration of VSMCs and attenuated neointimal hyperplasia, both in ligated mice carotid artery and cultured saphenous vein, which was mediated via a mechanism that involved AMPK activation. Importantly, the study highlighted the potential of AMA to be explored as a new drug candidate for neointimal hyperplasia.
最近的研究验证了口腔外苦味受体的表达，并确定了与这些受体的各种细胞生物学过程相关的调节功能的重要性。然而，苦味受体活性在新生内膜增生中的重要性尚未得到认可。苦味受体激活剂 amarogentin（AMA）已知可调节多种细胞信号，包括 AMP 激活蛋白激酶（AMPK）、STAT3、Akt、ERK 和 p53，这些信号与新生内膜增生有关。
本研究评估了 AMA 对新生内膜增生的影响，并探讨了潜在的机制。
无细胞毒性浓度的 AMA 可显著抑制血清（15% FBS）和 PDGF-BB 诱导的 VSMCs 的增殖和迁移。此外，AMA 还可显著抑制体外培养的大隐静脉和体内结扎的小鼠颈总动脉的新生内膜增生，而 AMA 对 VSMCs 的增殖和迁移的抑制作用是通过激活 AMPK 依赖性信号传导介导的，该信号传导可通过 AMPK 抑制来阻断。
本研究表明，AMA 可抑制 VSMCs 的增殖和迁移，并减轻结扎小鼠颈总动脉和培养的大隐静脉中的新生内膜增生，其机制涉及 AMPK 的激活。重要的是，该研究强调了 AMA 作为新生内膜增生新药物候选物的潜力。
