Kong Nickolette, Penaloza Natalia, Agreda Gustavo, Nguyen Angela B, Gutheinz Joseph, Tran Alison, Nguyen Nhi, Ho Tuong Vi, Marin Ana, Mellis Birgit, Chandra Richa
University of St. Thomas, Department of Chemistry and Biochemistry, 3800 Montrose Blvd, Houston, TX, 77006, USA.
University of St. Thomas, Department of Physics and Engineering, 3800 Montrose Blvd, Houston, TX, 77006, USA.
Biochem Biophys Rep. 2025 Feb 10;41:101945. doi: 10.1016/j.bbrep.2025.101945. eCollection 2025 Mar.
Cardiovascular disease (CVD) is the number one cause of mortality worldwide, with oxidative stress contributing significantly to its pathogenesis. Lipoproteins, key biomolecules in lipid transport, are particularly susceptible to oxidative modifications, which can contribute to atherogenesis. The need for advanced analytical tools to better understand the pathogenesis of cardiovascular disease (CVD) is critical due to its significant impact on public health. Clinicians often rely on indirect calculations of low-density lipoprotein (LDL) as a primary diagnostic indicator, which can oversimplify and overlook the complex changes in lipoprotein structure and function and therefore the complex etiology of CVD. Here it is demonstrated that dynamic light scattering (DLS) is sensitive and effective at measuring variation in lipoprotein size distributions following oxidative damage caused by peroxidation and nitration-two common physiological processes that play dual roles in both normal and pathogenic states. We establish the utility of DLS in detecting subtle variations in lipoprotein size, including potential aggregation and fission events resulting from chemical modifications. Our work highlights the value of DLS in advancing our understanding of the pathogenic mechanisms underlying CVD development, while also providing a foundational framework to study other biological processes and their effects on lipoproteins, ultimately guiding the development of therapies to address these harmful processes.
心血管疾病（CVD）是全球头号死因，氧化应激在其发病机制中起着重要作用。脂蛋白作为脂质转运中的关键生物分子，特别容易受到氧化修饰，这可能导致动脉粥样硬化的发生。由于心血管疾病（CVD）对公众健康有重大影响，因此需要先进的分析工具来更好地理解其发病机制。临床医生通常依赖于间接计算低密度脂蛋白（LDL）作为主要诊断指标，这可能会过度简化并忽略脂蛋白结构和功能的复杂变化，进而忽略心血管疾病的复杂病因。本文证明，动态光散射（DLS）在测量由过氧化和硝化引起的氧化损伤后脂蛋白大小分布的变化方面既敏感又有效，过氧化和硝化是两种常见的生理过程，在正常和致病状态下都起着双重作用。我们确立了DLS在检测脂蛋白大小细微变化方面的实用性，包括化学修饰导致的潜在聚集和裂变事件。我们的工作突出了DLS在增进我们对心血管疾病发展潜在致病机制理解方面的价值，同时也为研究其他生物过程及其对脂蛋白的影响提供了基础框架，最终指导应对这些有害过程的治疗方法的开发。
