Huang Jiayuan, Wu Jian, Wang Shijun, You Jieyun, Ye Yong, Ding Zhiwen, Yang Fenghua, Wang Xingxu, Guo Junjie, Ma Leilei, Yuan Jie, Shen Yunli, Yang Xiangdong, Sun Aijun, Jiang Hong, Bu Liping, Backx Peter H, Ge Junbo, Zou Yunzeng
Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital and Institutes of Biomedical Sciences, Fudan University, Shanghai, People's Republic of China.
Department of Cardiovascular Medicine, East Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China.
Am J Physiol Heart Circ Physiol. 2017 Jul 1;313(1):H138-H148. doi: 10.1152/ajpheart.00004.2017. Epub 2017 Apr 28.
In mice, myocardial hypertrophic preconditioning (HP), which is produced by the removal of short-term transverse aortic constriction (TAC), was recently reported to render the heart resistant to hypertrophic responses induced by subsequent reconstriction (Re-TAC). However, there is no efficient noninvasive method for ensuring that the repeated aortic manipulations were successfully performed. We previously demonstrated that ultrasound biomicroscopy (UBM) is a noninvasive and effective approach for predicting TAC success. Here, we investigated the value of UBM for serial predictions of load conditions in establishing a murine HP model. C57BL/6J mice were subjected to a sham operation, TAC, or Re-TAC, and the peak flow velocity at the aortic banding site (PVb) was measured by UBM. Left ventricular end-systolic pressure (LVESP) was examined by micromanometric catheterization. The PVb was positively associated with LVESP ( = 0.8204, < 0.001, for TAC at 3 days and = 0.7746, < 0.001, for Re-TAC at 4 wk). PVb and LVESP values were markedly elevated after aortic banding, became attenuated to the sham-operated level after debanding, and increased after aortic rebanding. The cardiac hypertrophic responses were examined by UBM, histology, RT-PCR, and Western blot analysis. Four weeks after the last operation, with PVb ≥ 3.5 m/s as an indicator of successful aortic constriction, Re-TAC mice showed less cardiac hypertrophy, fetal gene expression, and ERK1/2 activation than TAC mice. Therefore, we successfully established a UBM protocol for the serial assessment of aortic flow and the prediction of LVESP during repeated aortic manipulations in mice, which might be useful for noninvasive evaluations of the murine HP model. We successfully developed an ultrasound biomicroscopy protocol for the serial assessment of aortic bandings and the relevant left ventricular pressure in a murine model of cardiac hypertrophic preconditioning. The protocol may be of great importance in the successful establishment of the hypertrophic preconditioning model for further mechanistic and pharmacological studies.
在小鼠中，最近有报道称，通过去除短期主动脉缩窄（TAC）产生的心肌肥厚预处理（HP）可使心脏对随后再次缩窄（Re-TAC）诱导的肥厚反应产生抗性。然而，目前尚无有效的非侵入性方法来确保重复的主动脉操作成功进行。我们之前证明超声生物显微镜检查（UBM）是预测TAC成功的一种非侵入性有效方法。在此，我们研究了UBM在建立小鼠HP模型过程中对负荷条件进行系列预测的价值。将C57BL/6J小鼠进行假手术、TAC或Re-TAC处理，并通过UBM测量主动脉缩窄部位的峰值流速（PVb）。通过微测压导管检查左心室收缩末期压力（LVESP）。PVb与LVESP呈正相关（TAC术后3天，r = 0.8204，P < 0.001；Re-TAC术后4周，r = 0.7746，P < 0.001）。主动脉缩窄后PVb和LVESP值明显升高，解除缩窄后降至假手术水平，再次缩窄后又升高。通过UBM、组织学、RT-PCR和蛋白质印迹分析来检测心脏肥厚反应。在最后一次手术后4周，以PVb≥3.5 m/s作为主动脉缩窄成功的指标，Re-TAC小鼠的心脏肥大、胎儿基因表达和ERK1/2激活程度均低于TAC小鼠。因此，我们成功建立了一种UBM方案，用于在小鼠重复主动脉操作过程中对主动脉血流进行系列评估并预测LVESP，这可能有助于对小鼠HP模型进行非侵入性评估。我们成功开发了一种超声生物显微镜方案，用于在心脏肥厚预处理的小鼠模型中对主动脉缩窄及相关左心室压力进行系列评估。该方案对于成功建立肥厚预处理模型以进行进一步的机制和药理学研究可能具有重要意义。
