Tjandrawinata Raymond Rubianto, Vencio Isabela Caiado Caixeta, Nugroho Axel Brahmantyo Maynardo, Hartanto Jonathan, Widjanarko Nicolas Daniel, Nurkolis Fahrul
Center for Pharmaceutical and Nutraceutical Research and Policy, Faculty of Biotechnology, Atma Jaya Catholic University of Indonesia, Jakarta, 12930, Indonesia.
Pontificial Catholic University of Sao Paulo, São Paulo, 05014-901, SP, Brasil.
Diabetol Metab Syndr. 2025 Jul 25;17(1):293. doi: 10.1186/s13098-025-01868-5.
This review explores unique molecular and biochemical adaptations in sharks and whales that confer resistance to atherosclerosis despite high lipid concentrations, unlike atherosclerosis-prone terrestrial mammals (e.g., humans, primates) and shorter-lived marine species (e.g., seals, dolphins). Central to our hypothesis is that sharks and whales evolved unique lipid quality management, specialized peptide systems, and genomic expansions beyond ubiquitous marine omega-3 polyunsaturated fatty acids (PUFAs) to prevent plaque formation. Comparative lipidomics highlights marine-specific profiles rich in anti-inflammatory omega-3 PUFAs, contributing to vascular protection and plaque prevention. Sharks demonstrate potent anti-angiogenic peptides and aminosterols (e.g., squalamine, trodusquemine) that modulate key pathways like PTP1B inhibition, thus reducing inflammation and endothelial dysfunction. Whales exhibit specialized lipid metabolites in blubber, including esterified omega-3 PUFAs, enhancing antioxidant enzyme activity and endothelial nitric oxide production, crucial for maintaining vascular health. Genomic insights further reveal expanded antioxidant gene families in whales, highlighting potential translational strategies to human cardiovascular therapies. Future therapeutic strategies must resolve challenges in ethical sourcing, bioavailability, and scalability. CLINICAL TRIAL NUMBER: Not applicable.
本综述探讨了鲨鱼和鲸鱼独特的分子和生化适应性，这些适应性使它们尽管脂质浓度很高，但仍能抵抗动脉粥样硬化，这与易患动脉粥样硬化的陆生哺乳动物（如人类、灵长类动物）和寿命较短的海洋物种（如海豹、海豚）不同。我们假设的核心是，鲨鱼和鲸鱼进化出了独特的脂质质量管理、专门的肽系统以及除普遍存在的海洋ω-3多不饱和脂肪酸（PUFA）之外的基因组扩张，以防止斑块形成。比较脂质组学突出了富含抗炎ω-3多不饱和脂肪酸的海洋特异性谱，有助于血管保护和斑块预防。鲨鱼展示了强大的抗血管生成肽和氨基甾醇（如鲨胺、曲古抑菌素），它们调节关键途径，如抑制蛋白酪氨酸磷酸酶1B（PTP1B），从而减轻炎症和内皮功能障碍。鲸鱼在鲸脂中表现出特殊的脂质代谢产物，包括酯化的ω-3多不饱和脂肪酸，增强抗氧化酶活性和内皮一氧化氮生成，这对维持血管健康至关重要。基因组学见解进一步揭示了鲸鱼中扩展的抗氧化基因家族，突出了对人类心血管治疗的潜在转化策略。未来的治疗策略必须解决伦理采购、生物利用度和可扩展性方面的挑战。临床试验编号：不适用。
