Lin Fang, Ding Yue, Liang Xiaoting
Institute for Regenerative Medicine, Shanghai East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, China.
Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Tongji University, Shanghai, China.
Cardiol Res Pract. 2024 Oct 28;2024:9395213. doi: 10.1155/2024/9395213. eCollection 2024.
In the elderly population, coronary heart disease (CHD) often coexists with hypertension. However, excessive blood pressure reduction can paradoxically increase the incidence of adverse events. Understanding the molecular mechanisms underlying hypertension and CHD in aged populations is crucial for developing targeted therapies and improving clinical outcomes. In this study, we constructed myocardial infarction (MI) and transverse aortic constriction (TAC) modelsY in aged mice to simulate the disease states of CHD and hypertension, respectively. Using integrated proteomic and phosphoproteomic analyses, we investigated the molecular signatures associated with MI and TAC in these models. Our aim was to identify key molecules involved in these conditions and to understand their unique and shared characteristics. Through our comprehensive proteomic and phosphoproteomic analysis, we identified a total of 1583 proteins and 232 phosphorylated proteins. We observed significant upregulation of heart disease markers such as Myh7, Xirp2, and Acta1, indicating the successful establishment of the MI and TAC models. The overlapped differentially expressed proteins (DEPs) and differentially phosphorylated proteins (DPPs) in MI and TAC were involved in heart failure-related processes including cardiac muscle contraction and hypertrophic cardiomyopathy, further supporting the validity of the models. Among the DEPs, Ppme1 was upregulated in the TAC model but downregulated in the MI model, while Sec31a and Gm56451 displayed the opposite expression patterns. Among the DPPs, Ablim1 and Atp2a2 were found to be significantly upregulated in the TAC model, whereas their expression was markedly reduced in the MI model. In addition, five other DPPs, including REV_Q3TAY5, Cbx3, PITPNB, Eif4b, and A0A1Y7VP73, were elevated in the MI model but decreased in the TAC model. In conclusion, these findings suggest that MI and TAC not only share certain molecular features but also retain their unique characteristics, providing potential biomarkers and therapeutic targets.
在老年人群中，冠心病（CHD）常与高血压并存。然而，过度降低血压反而会增加不良事件的发生率。了解老年人群中高血压和冠心病的分子机制对于开发靶向治疗方法和改善临床结局至关重要。在本研究中，我们在老年小鼠中构建了心肌梗死（MI）和主动脉缩窄（TAC）模型，分别模拟冠心病和高血压的疾病状态。使用蛋白质组学和磷酸化蛋白质组学综合分析，我们研究了这些模型中与MI和TAC相关的分子特征。我们的目的是识别参与这些病症的关键分子，并了解它们的独特和共同特征。通过全面的蛋白质组学和磷酸化蛋白质组学分析，我们共鉴定出1583种蛋白质和232种磷酸化蛋白质。我们观察到心脏病标志物如Myh7、Xirp2和Acta1显著上调，表明MI和TAC模型成功建立。MI和TAC中重叠的差异表达蛋白（DEP）和差异磷酸化蛋白（DPP）参与了与心力衰竭相关的过程，包括心肌收缩和肥厚性心肌病，进一步支持了模型的有效性。在DEP中，Ppme1在TAC模型中上调，但在MI模型中下调，而Sec31a和Gm56451表现出相反的表达模式。在DPP中，发现Ablim1和Atp2a2在TAC模型中显著上调，而它们在MI模型中的表达明显降低。此外，其他五种DPP，包括REV_Q3TAY5、Cbx3、PITPNB、Eif4b和A0A1Y7VP73，在MI模型中升高，但在TAC模型中降低。总之，这些发现表明MI和TAC不仅具有某些共同的分子特征，而且保留了各自的独特特征，为潜在的生物标志物和治疗靶点提供了依据。
