Stephens Victoria R, Ameli Sharareh, Major Amy S, Wanjalla Celestine N
Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Division of Infectious Diseases, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Int J Mol Sci. 2025 Apr 5;26(7):3417. doi: 10.3390/ijms26073417.
Cardiovascular disease (CVD) remains the leading cause of death worldwide. Several factors are implicated in the pathogenesis of CVD, and efforts have been made to reduce traditional risks, yet CVD remains a complex burden. Notably, people living with HIV (PLWH) are twice as likely to develop CVD compared to persons without HIV (PWoH). Intensive statin therapy, the first-line treatment to prevent cardiovascular events, is effective at reducing morbidity and mortality. However, statin therapy has not reduced the overall prevalence of CVD. Despite antiretroviral therapy (ART), and new guidelines for statin use, PLWH have persistent elevation of inflammatory markers, which is suggested to be a bigger driver of future cardiovascular events than low-density lipoprotein. Herein, we have summarized the development of atherosclerosis and highlighted mouse models of atherosclerosis in the presence and absence of HIV. Since most mouse strains have several mechanisms that are atheroprotective, researchers have developed mouse models to study CVD using dietary and genetic manipulations. In evaluating the current methodologies for studying HIV-associated atherosclerosis, we have detailed the benefits of integrating multi-omics analyses, genetic manipulations, and immune cell profiling within mouse models. These advanced approaches significantly enhance our capacity to address critical gaps in understanding the immune mechanisms driving CVD, including in the context of HIV.
心血管疾病（CVD）仍然是全球主要的死亡原因。CVD的发病机制涉及多个因素，人们已努力降低传统风险，但CVD仍然是一个复杂的负担。值得注意的是，与未感染艾滋病毒的人（PWoH）相比，感染艾滋病毒的人（PLWH）患CVD的可能性要高两倍。强化他汀类药物治疗作为预防心血管事件的一线治疗方法，在降低发病率和死亡率方面是有效的。然而，他汀类药物治疗并未降低CVD的总体患病率。尽管有抗逆转录病毒疗法（ART）以及他汀类药物使用的新指南，但PLWH的炎症标志物持续升高，这被认为是未来心血管事件比低密度脂蛋白更大的驱动因素。在此，我们总结了动脉粥样硬化的发展，并强调了存在和不存在艾滋病毒情况下的动脉粥样硬化小鼠模型。由于大多数小鼠品系具有多种抗动脉粥样硬化机制，研究人员已通过饮食和基因操作开发了用于研究CVD的小鼠模型。在评估当前研究与艾滋病毒相关的动脉粥样硬化的方法时，我们详细阐述了在小鼠模型中整合多组学分析、基因操作和免疫细胞分析的益处。这些先进方法显著增强了我们解决理解驱动CVD的免疫机制（包括在艾滋病毒背景下）关键差距的能力。
