乔刚
阜外华中心血管病医院 大血管外科
OBJECTIVES: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.MATERIALS AND METHODS:The present study assessed the effects of AMA on neointimal hyperplasia and explored the potential underlying mechanisms.RESULTS: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.CONCLUSION: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.
Biochimica et biophysica acta. Molecular basis of disease 2023
OBJECTIVES:To study the impact of a balloon occlusion (BO) technique in stented elephant trunk implantation in Sun's procedure for acute Stanford type A aortic dissection (AAAD) on important postoperative organ complications and patient rehabilitation.METHODS:Eighty-five patients with AAAD who underwent Sun's procedure from January 2019 to January 2020 were selected. Cases were divided into two groups based on whether the aortic BO technique was used in stented elephant trunk implantation: the BO group and the nonballoon occlusion (NBO) group. The collected data included the patients' clinical characteristics, operative data, postoperative complications and recovery. We applied statistical software to study the impact of a BO technique in stented elephant trunk implantation in Sun's procedure.RESULTS:A total of 85 patients with AAAD underwent Sun's procedure. A total of 29 used BO technique, 56 did not use. The circulatory arrest time in the BO group was controlled within 8.07 ± 2.33 min, and the nasopharyngeal temperature dropped to 28°C. Overall postoperative complications were less frequent in BO group than NBO group (52% vs. 75%; p = .030). Using BO technique, we reduced the 24-h drainage volume, and lowered the occurrence of hypoxemia (48%), liver dysfunction (10%), and median tracheal intubation time was 37 h (range: 12.5-106 h), median intensive care unit (ICU) time was 65 h (range: 17-207 h).CONCLUSIONS:During total aortic arch replacement and stented elephant trunk surgery for AAAD, we used the aortic BO technique, which avoids deeper hypothermia and effectively shortens circulatory arrest times. This approach is helpful for reducing the incidence of postoperative complications and shortening the intensive care unit time. This method also reduces the patient's medical burden and facilitates faster recovery.
Journal of cardiac surgery 2022
This study was designed to determine the effects of the long non-coding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) on vascular smooth muscle cell (VSMC) apoptosis and extracellular matrix (ECM) disruption in a murine abdominal aortic aneurysm (AAA) model. After injection of PVT1-silencing lentiviruses, AAA was induced in Apolipoprotein E-deficient (ApoE-/-) male mice by angiotensin II (Ang II) infusion for four weeks. After Ang II infusion, mouse serum levels of pro-inflammatory cytokines were analysed, and aortic tissues were isolated for histological, RNA, and protein analysis. Our results also showed that PVT1 expression was significantly upregulated in abdominal aortic tissues from AAA patients compared with that in controls. Additionally, Ang II treatment significantly increased PVT1 expression, both in cultured mouse VSMCs and in AAA murine abdominal aortic tissues. Of note, the effects of Ang II in facilitating cell apoptosis, increasing matrix metalloproteinase (MMP)-2 and MMP-9, reducing tissue inhibitor of MMP (TIMP)-1, and promoting switching from the contractile to synthetic phenotype in cultured VSMCs were enhanced by overexpression of PVT1 but attenuated by knockdown of PVT1. Furthermore, knockdown of PVT1 reversed Ang II-induced AAA-associated alterations in mice, as evidenced by attenuation of aortic diameter dilation, marked adventitial thickening, loss of elastin in the aorta, enhanced aortic cell apoptosis, elevated MMP-2 and MMP-9, reduced TIMP-1, and increased pro-inflammatory cytokines. In conclusion, our findings demonstrate that knockdown of lncRNA PVT1 suppresses VSMC apoptosis, ECM disruption, and serum pro-inflammatory cytokines in a murine Ang II-induced AAA model.
Molecules and cells 2019
