Farnesyltransferase (FTase) is an important enzyme that catalyses the modification of protein isoprene downstream of the mevalonate pathway. Previous studies have shown that the tissue of the heart in the suprarenal abdominal aortic coarctation (AAC) group showed overexpression of FTaseβ (FNTB) and the activation of the downstream protein Ras was enhanced. FTase inhibitor (FTI) can alleviate myocardial fibrosis and partly improve cardiac remodelling in spontaneously hypertensive rats. However, the exact role and mechanism of FTase in myocardial hypertrophy and remodelling are not fully understood. Here, we used recombinant adenovirus to transfect neonatal rat ventricular cardiomyocytes to study the effect of FNTB overexpression on myocardial remodelling and explore potential mechanisms. The results showed that overexpression of FNTB induces neonatal rat ventricular myocyte hypertrophy and reduces the survival rate of cardiomyocytes. FNTB overexpression induced a decrease in mitochondrial membrane potential and increased apoptosis in cardiomyocytes. FNTB overexpression also promotes autophagosome formation and the accumulation of autophagy substrate protein, LC3II. Transmission electron microscopy (TEM) and mCherry‐GFP tandem fluorescent‐tagged LC3 (tfLC3) showed that FNTB overexpression can activate autophagy flux by enhancing autophagosome conversion to autophagolysosome. Overactivated autophagy flux can be blocked by bafilomycin A1. In addition, salirasib (a Ras farnesylcysteine mimetic) can alleviate the hypertrophic phenotype of cardiomyocytes and inhibit the up‐regulation of apoptosis and autophagy flux induced by FNTB overexpression. These results suggest that FTase may have a potential role in future treatment strategies to limit the adverse consequences of cardiac hypertrophy, cardiac dysfunction and heart failure.

中文翻译：

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FNTB的过度表达和Ras的激活诱导心肌细胞肥大并促进细胞凋亡和自噬细胞死亡。

法呢基转移酶（FTase）是一种重要的酶，可催化甲羟戊酸途径下游的蛋白质异戊二烯的修饰。先前的研究表明，肾上腹主动脉缩窄（AAC）组的心脏组织显示FTaseβ（FNTB）的过表达，并且下游蛋白Ras的激活得到增强。FTase抑制剂（FTI）可以减轻自发性高血压大鼠的心肌纤维化并部分改善心脏重构。但是，FTase在心肌肥大和重塑中的确切作用和机制尚不完全清楚。在这里，我们使用重组腺病毒转染新生大鼠心室心肌细胞，以研究FNTB过表达对心肌重塑的影响并探讨潜在的机制。结果表明，FNTB的过表达诱导新生大鼠心室肌细胞肥大，并降低了心肌细胞的存活率。FNTB的过度表达导致线粒体膜电位的降低和心肌细胞凋亡的增加。FNTB的过表达还促进自噬体的形成和自噬底物蛋白LC3II的积累。透射电子显微镜（TEM）和mCherry-GFP串联荧光标记的LC3（tfLC3）表明FNTB过表达可以通过增强自噬体转化为自噬体而激活自噬通量。过度活化的自噬通量可以被bafilomycin A1阻断。此外，salirasib（Ras法呢基半胱氨酸模拟物）可以缓解心肌细胞的肥大表型，并抑制FNTB过表达诱导的细胞凋亡和自噬通量的上调。这些结果表明，FTase在未来治疗策略中可能具有潜在作用，以限制心脏肥大，心脏功能障碍和心力衰竭的不良后果。