Lindsey Merry L, Goshorn Danielle K, Comte-Walters Susana, Hendrick Jennifer W, Hapke Elizabeth, Zile Michael R, Schey Kevin
Division of Cardiothoracic Surgery Research, Department of Surgery, Medical University of South Carolina, Charleston, SC, USA.
Proteomics. 2006 Apr;6(7):2225-35. doi: 10.1002/pmic.200500013.
Left ventricular hypertrophy (LVH) is a leading cause of congestive heart failure. The exact mechanisms that control cardiac growth and regulate the transition to failure are not fully understood, in part due to the lack of a complete inventory of proteins associated with LVH. We investigated the proteomic basis of LVH using the transverse aortic constriction model of pressure overload in mice coupled with a multidimensional approach to identify known and novel proteins that may be relevant to the development and maintenance of LVH. We identified 123 proteins that were differentially expressed during LVH, including LIM proteins, thioredoxin, myoglobin, fatty acid binding protein 3, the abnormal spindle-like microcephaly protein (ASPM), and cytoskeletal proteins such as actin and myosin. In addition, proteins with unknown functions were identified, providing new directions for future research in this area. We also discuss common pitfalls and strategies to overcome the limitations of current proteomic technologies. Together, the multidimensional approach provides insight into the proteomic changes that occur in the LV during hypertrophy.
左心室肥厚(LVH)是充血性心力衰竭的主要原因。控制心脏生长并调节向心力衰竭转变的确切机制尚未完全明确,部分原因是缺乏与LVH相关蛋白质的完整清单。我们使用小鼠压力超负荷的横向主动脉缩窄模型,结合多维方法来鉴定可能与LVH的发生和维持相关的已知和新型蛋白质,从而研究LVH的蛋白质组学基础。我们鉴定出123种在LVH期间差异表达的蛋白质,包括LIM蛋白、硫氧还蛋白、肌红蛋白、脂肪酸结合蛋白3、异常纺锤样小头畸形蛋白(ASPM)以及肌动蛋白和肌球蛋白等细胞骨架蛋白。此外,还鉴定出了功能未知的蛋白质,为该领域未来的研究提供了新方向。我们还讨论了常见的陷阱以及克服当前蛋白质组学技术局限性的策略。总之,多维方法为深入了解肥厚过程中左心室发生的蛋白质组学变化提供了思路。