Mukhopadhyay Partha, Yokus Burhan, Paes-Leme Bruno, Bátkai Sándor, Ungvári Zoltán, Haskó György, Pacher Pal
Laboratory of Cardiovascular Physiology and Tissue Injury, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA.
Vascular Cognitive Impairment, Neurodegeneration, and Healthy Brain Aging Program, Department of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Geroscience. 2025 Mar 20. doi: 10.1007/s11357-025-01613-w.
The pathology of cardiovascular aging is complex, involving mitochondrial dysfunction, oxidative and nitrative stress, oxidative DNA injury, impaired lipid metabolism, cell death, senescence, and chronic inflammation. These processes lead to remodeling and structural changes in the cardiovascular system, resulting in a progressive decline in cardiovascular reserve capacity and health, and an increased risk of diseases and mortality. Excessive alcohol consumption exacerbates these risks by promoting hypertension, stroke, arrhythmias, coronary artery disease, cardiomyopathy, and sudden cardiac death, yet the effects of chronic alcohol consumption on cardiovascular aging remain unclear. Herein, we explored the impact of a 6-month 5% Lieber-DeCarli alcohol diet in young (3 months old) and aging (24-26 months old) Fisher F344BNF1 rats. We assessed detailed hemodynamics, mitochondrial function, oxidative/nitrative stress, lipid metabolism, inflammation, cell death, senescence, and myocardial fibrosis using the pressure-volume system, isolated vascular rings, and various histological, biochemical, and molecular biology methods. Alcohol consumption in both young and aging rats impaired mitochondrial function, disrupted cholesterol and triglyceride metabolism, and increased oxidative/nitrative stress, inflammation, cell death, and senescence, leading to a decline in systolic contractile function. In aging rats, alcohol further exacerbated diastolic dysfunction and myocardial fibrosis. Alcohol also increased oxidative/nitrative stress, apoptosis, and senescence in the vasculature, contributing to endothelial dysfunction and increased total peripheral resistance. Additionally, alcohol exacerbated the aging-related ventriculo-arterial uncoupling and diminished cardiac efficiency, further reducing cardiovascular reserve capacity. In conclusion, chronic alcohol consumption promotes cardiovascular aging and further diminishes the already impaired cardiac and vascular reserve capacity associated with aging.
心血管衰老的病理过程复杂，涉及线粒体功能障碍、氧化应激和硝化应激、氧化性DNA损伤、脂质代谢受损、细胞死亡、衰老以及慢性炎症。这些过程导致心血管系统重塑和结构变化，致使心血管储备能力和健康状况逐渐下降，疾病风险和死亡率增加。过量饮酒会通过引发高血压、中风、心律失常、冠状动脉疾病、心肌病和心源性猝死来加剧这些风险，然而长期饮酒对心血管衰老的影响仍不明确。在此，我们探究了为期6个月的5% Lieber-DeCarli酒精饮食对年轻（3个月大）和老龄（24 - 26个月大）的Fisher F344BNF1大鼠的影响。我们使用压力 - 容积系统、离体血管环以及各种组织学、生物化学和分子生物学方法，评估了详细的血流动力学、线粒体功能、氧化/硝化应激、脂质代谢、炎症、细胞死亡、衰老和心肌纤维化情况。年轻和老龄大鼠饮酒均损害了线粒体功能，扰乱了胆固醇和甘油三酯代谢，增加了氧化/硝化应激、炎症、细胞死亡和衰老，导致收缩期收缩功能下降。在老龄大鼠中，酒精进一步加剧了舒张功能障碍和心肌纤维化。酒精还增加了血管中的氧化/硝化应激、细胞凋亡和衰老，导致内皮功能障碍和总外周阻力增加。此外，酒精加剧了与衰老相关的心室 - 动脉解耦联并降低了心脏效率，进一步降低了心血管储备能力。总之，长期饮酒会促进心血管衰老，并进一步降低与衰老相关的已受损的心脏和血管储备能力。
