Pietrangelo Donatella, Lopa Caroline, Litterio Margherita, Cotugno Maria, Rubattu Speranza, Lombardi Angela
Department of Clinical and Molecular Medicine, School of Medicine and Psychology, Sapienza University of Rome, 00189 Rome, Italy.
IRCCS Neuromed, 86077 Pozzilli, IS, Italy.
Int J Mol Sci. 2025 Jul 15;26(14):6791. doi: 10.3390/ijms26146791.
The study of metabolic abnormalities regarding mitochondrial respiration and energy production has significantly advanced our understanding of cell biology and molecular mechanisms underlying cardiovascular diseases (CVDs). Mitochondria provide 90% of the energy required for maintaining normal cardiac function and are central to heart bioenergetics. During the initial phase of heart failure, mitochondrial number and function progressively decline, causing a decrease in oxidative metabolism and increased glucose uptake and glycolysis, leading to ATP depletion and bioenergetic starvation, finally contributing to overt heart failure. Compromised mitochondrial bioenergetics is associated with vascular damage in hypertension, vascular remodeling in pulmonary hypertension and acute cardiovascular events. Thus, mitochondrial dysfunction, leading to impaired ATP production, excessive ROS generation, the opening of mitochondrial permeability transition pores and the activation of apoptotic and necrotic pathways, is revealed as a typical feature of common CVDs. Molecules able to positively modulate cellular metabolism by improving mitochondrial bioenergetics and energy metabolism and inhibiting oxidative stress production are expected to exert beneficial protective effects in the heart and vasculature. This review discusses recent advances in cardiovascular research through the study of cellular bioenergetics in both chronic and acute CVDs. Emerging therapeutic strategies, specifically targeting metabolic modulators, mitochondrial function and quality control, are discussed.
关于线粒体呼吸和能量产生的代谢异常研究，极大地推进了我们对心血管疾病（CVD）潜在细胞生物学和分子机制的理解。线粒体提供维持正常心脏功能所需能量的90%，是心脏生物能量学的核心。在心力衰竭的初始阶段，线粒体数量和功能逐渐下降，导致氧化代谢减少，葡萄糖摄取和糖酵解增加，进而导致ATP耗竭和生物能量饥饿，最终促成明显的心力衰竭。线粒体生物能量学受损与高血压中的血管损伤、肺动脉高压中的血管重塑以及急性心血管事件相关。因此，线粒体功能障碍导致ATP生成受损、过量ROS产生、线粒体通透性转换孔开放以及凋亡和坏死途径激活，被揭示为常见CVD的典型特征。有望通过改善线粒体生物能量学和能量代谢以及抑制氧化应激产生来正向调节细胞代谢的分子，在心脏和血管系统中发挥有益的保护作用。本综述通过研究慢性和急性CVD中的细胞生物能量学，讨论心血管研究的最新进展。还讨论了新兴的治疗策略，特别是针对代谢调节剂、线粒体功能和质量控制的策略。
