The Frick Center for Heart Failure and Arrhythmia, The Dorothy M. Davis Heart and Lung Research Institute, the Ohio State University Wexner Medical Center, Columbus, OH, USA.
Department of Biomedical Engineering, College of Engineering, the Ohio State University, Columbus, OH, USA.
Expert Opin Ther Targets. 2022 Jan;26(1):29-40. doi: 10.1080/14728222.2022.2031974. Epub 2022 Jan 27.
Cardiac hypertrophy is associated with adverse outcomes across cardiovascular disease states. Despite strides over the last three decades in identifying molecular and cellular mechanisms driving hypertrophy, the link between pathophysiological stress stimuli and specific myocyte/heart growth profiles remains unclear. Moreover, the optimal strategy for preventing pathology in the setting of hypertrophy remains controversial.
This review discusses molecular mechanisms underlying cardiac hypertrophy with a focus on factors driving the orientation of myocyte growth and the impact on heart function. We highlight recent work showing a novel role for the spectrin-based cytoskeleton, emphasizing regulation of myocyte dimensions but not hypertrophy per se. Finally, we consider opportunities for directing the orientation of myocyte growth in response to hypertrophic stimuli as an alternative therapeutic approach. Relevant publications on the topic were identified through Pubmed with open-ended search dates.
To define new therapeutic avenues, more precision is required when describing changes in myocyte and heart structure/function in response to hypertrophic stimuli. Recent developments in computational modeling of hypertrophic networks, in concert with more refined experimental approaches will catalyze translational discovery to advance the field and further our understanding of cardiac hypertrophy and its relationship with heart disease.
心肌肥厚与心血管疾病状态的不良结局相关。尽管在过去三十年中,人们在确定驱动肥厚的分子和细胞机制方面取得了进展,但病理生理应激刺激与特定心肌/心脏生长特征之间的联系仍不清楚。此外,在肥厚的情况下预防病理学的最佳策略仍存在争议。
本文讨论了心肌肥厚的分子机制,重点介绍了驱动心肌生长方向的因素及其对心脏功能的影响。我们强调了最近的工作,表明基于血影蛋白的细胞骨架在调节心肌细胞尺寸方面具有新的作用,但本身并不引起心肌肥厚。最后,我们考虑了在应对肥厚刺激时指导心肌生长方向的机会,作为一种替代的治疗方法。通过 Pubmed 进行了开放式搜索日期的主题相关出版物的识别。
为了确定新的治疗途径,在描述对肥厚刺激的心肌和心脏结构/功能的变化时,需要更精确。在肥厚网络的计算模型方面的最新进展,以及更精细的实验方法,将促进转化发现,推动该领域的发展,并进一步加深我们对心肌肥厚及其与心脏病关系的理解。