Department of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, AL 35233, USA.
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
J Mol Cell Cardiol. 2024 Mar;188:52-60. doi: 10.1016/j.yjmcc.2024.01.005. Epub 2024 Feb 9.
From molecular and cellular perspectives, heart failure is caused by the loss of cardiomyocytes-the fundamental contractile units of the heart. Because mammalian cardiomyocytes exit the cell cycle shortly after birth, the cardiomyocyte damage induced by myocardial infarction (MI) typically leads to dilatation of the left ventricle (LV) and often progresses to heart failure. However, recent findings indicate that the hearts of neonatal pigs completely regenerated the cardiomyocytes that were lost to MI when the injury occurred on postnatal day 1 (P1). This recovery was accompanied by increases in the expression of markers for cell-cycle activity in cardiomyocytes. These results suggest that the repair process was driven by cardiomyocyte proliferation. This review summarizes findings from recent studies that found evidence of cardiomyocyte proliferation in 1) the uninjured hearts of newborn pigs on P1, 2) neonatal pig hearts after myocardial injury on P1, and 3) the hearts of pigs that underwent apical resection surgery (AR) on P1 followed by MI on postnatal day 28 (P28). Analyses of cardiomyocyte single-nucleus RNA sequencing data collected from the hearts of animals in these three experimental groups, their corresponding control groups, and fetal pigs suggested that although the check-point regulators and other molecules that direct cardiomyocyte cell-cycle progression and proliferation in fetal, newborn, and postnatal pigs were identical, the mechanisms that activated cardiomyocyte proliferation in response to injury may differ from those that regulate cardiomyocyte proliferation during development.
从分子和细胞的角度来看，心力衰竭是由心肌细胞的丧失引起的——心肌细胞是心脏的基本收缩单位。由于哺乳动物心肌细胞在出生后不久就退出了细胞周期，因此心肌梗死（MI）引起的心肌细胞损伤通常会导致左心室（LV）扩张，并常常进展为心力衰竭。然而，最近的发现表明，当损伤发生在出生后第 1 天（P1）时，新生猪的心脏完全再生了因 MI 而丧失的心肌细胞。这种恢复伴随着心肌细胞中细胞周期活性标志物表达的增加。这些结果表明，修复过程是由心肌细胞增殖驱动的。这篇综述总结了最近的研究结果，这些研究结果在以下三个方面发现了心肌细胞增殖的证据：1）在 P1 时未受伤的新生猪心脏，2）在 P1 时心肌损伤后的新生猪心脏，以及 3）在 P1 时接受心尖切除术（AR）后在 P28 时发生 MI 的猪的心脏。对来自这三个实验组、相应对照组和胎儿猪心脏的动物的心肌细胞单细胞 RNA 测序数据进行分析表明，尽管在胎儿、新生和新生猪中指导心肌细胞细胞周期进展和增殖的检查点调节剂和其他分子是相同的，但激活心肌细胞增殖以应对损伤的机制可能与调节心肌细胞增殖的机制不同在发育过程中。
