Merk Dennis, Cox Fiona Frederike, Jakobs Philipp, Prömel Simone, Altschmied Joachim, Haendeler Judith
Environmentally-Induced Cardiovascular Degeneration, Clinical Chemistry and Laboratory Diagnostics, Medical Faculty, University Hospital and Heinrich-Heine-University, 40225 Düsseldorf, Germany.
Medical Faculty, Institute for Translational Pharmacology, University Hospital and Heinrich-Heine-University, 40225 Düsseldorf, Germany.
Antioxidants (Basel). 2024 Apr 9;13(4):443. doi: 10.3390/antiox13040443.
The endothelium, the innermost cell layer of blood vessels, is not only a physical barrier between the bloodstream and the surrounding tissues but has also essential functions in vascular homeostasis. Therefore, it is not surprising that endothelial dysfunction is associated with most cardiovascular diseases. The functionality of the endothelium is compromised by endotoxemia, the presence of bacterial endotoxins in the bloodstream with the main endotoxin lipopolysaccharide (LPS). Therefore, this review will focus on the effects of LPS on the endothelium. Depending on the LPS concentration, the outcomes are either sepsis or, at lower concentrations, so-called low-dose or metabolic endotoxemia. Sepsis, a life-threatening condition evoked by hyperactivation of the immune response, includes breakdown of the endothelial barrier resulting in failure of multiple organs. A deeper understanding of the underlying mechanisms in the endothelium might help pave the way to new therapeutic options in sepsis treatment to prevent endothelial leakage and fatal septic shock. Low-dose endotoxemia or metabolic endotoxemia results in chronic inflammation leading to endothelial cell senescence, which entails endothelial dysfunction and thus plays a critical role in cardiovascular diseases. The identification of compounds counteracting senescence induction in endothelial cells might therefore help in delaying the onset or progression of age-related pathologies. Interestingly, two natural plant-derived substances, caffeine and curcumin, have shown potential in preventing endothelial cell senescence.
血管内皮是血管最内层的细胞层，它不仅是血流与周围组织之间的物理屏障，而且在血管稳态中具有重要功能。因此，内皮功能障碍与大多数心血管疾病相关也就不足为奇了。内毒素血症会损害内皮功能，内毒素血症是指血流中存在细菌内毒素，主要内毒素为脂多糖（LPS）。因此，本综述将聚焦于LPS对内皮的影响。根据LPS浓度的不同，结果可能是脓毒症，或者在较低浓度下是所谓的低剂量或代谢性内毒素血症。脓毒症是一种由免疫反应过度激活引起的危及生命的病症，包括内皮屏障的破坏，导致多器官功能衰竭。深入了解内皮中的潜在机制可能有助于为脓毒症治疗的新疗法铺平道路，以防止内皮渗漏和致命的感染性休克。低剂量内毒素血症或代谢性内毒素血症会导致慢性炎症，进而导致内皮细胞衰老，这会引发内皮功能障碍，因此在心血管疾病中起关键作用。因此，鉴定能够对抗内皮细胞衰老诱导的化合物可能有助于延缓与年龄相关疾病的发生或进展。有趣的是，两种天然植物来源的物质，咖啡因和姜黄素，已显示出预防内皮细胞衰老的潜力。
