Translational opportunities of single-cell biology in atherosclerosis.

Single-cell biology is bringing new clinical meaning to patient heterogeneity in many disciplines. Atlases of the cellular building blocks of the human atherosclerotic plaque have so far shown that: (i) cellular identity is overall preserved, albeit overlapping transcriptional programmes are activated; (ii) changes in cellular cluster abundance appear between healthy and diseased vascular states; (iii) renewed evidence emerged for a role of T cells in human cardiovascular disease (CVD); and (iv) macrophage heterogeneity supports targeting inflammation and lipids while sparing protective subsets. Vascular single-cell biology has clear translational implications for CVD in terms of identification of the molecular pathways of disease resistance vs. disease propensity and genetic risk, guidance in designing new therapies, vaccines and repurposing drugs for CVD, the study of the therapy-induced adaptation of plaque and circulating cells in clinical trials, improved modelling of human CVD through the availability of metagenomic data sets, and advances in patient selection and stratification. GMZB, Granzyme B; Lef1, lymphoid enhancer binding factor 1; Prf1 Perforin 1; Trem2, triggering receptor expressed on myeloid cells 2. The advent of single-cell biology opens a new chapter for understanding human biological processes and for diagnosing, monitoring, and treating disease. This revolution now reaches the field of cardiovascular disease (CVD). New technologies to interrogate CVD samples at single-cell resolution are allowing the identification of novel cell communities that are important in shaping disease development and direct towards new therapeutic strategies. These approaches have begun to revolutionize atherosclerosis pathology and redraw our understanding of disease development. This review discusses the state-of-the-art of single-cell analysis of atherosclerotic plaques, with a particular focus on human lesions, and presents the current resolution of cellular subpopulations and their heterogeneity and plasticity in relation to clinically relevant features. Opportunities and pitfalls of current technologies as well as the clinical impact of single-cell technologies in CVD patient care are highlighted, advocating for multidisciplinary and international collaborative efforts to join the cellular dots of CVD.

单细胞生物学在许多学科中为患者的异质性赋予了新的临床意义。到目前为止，人类动脉粥样硬化斑块的细胞组成图谱表明：（i）细胞特性总体上得以保留，尽管重叠的转录程序被激活；（ii）在健康和患病的血管状态之间，细胞群丰度发生变化；（iii）有新的证据表明T细胞在人类心血管疾病（CVD）中起作用；（iv）巨噬细胞的异质性支持针对炎症和脂质进行靶向治疗，同时保留具有保护作用的亚群。血管单细胞生物学在识别疾病抵抗与疾病倾向的分子途径以及遗传风险、指导设计新的心血管疾病治疗方法、疫苗和药物再利用、研究临床试验中斑块和循环细胞对治疗的适应性、通过宏基因组数据集的可用性改进人类心血管疾病建模以及患者选择和分层方面的进展等方面，对心血管疾病具有明确的转化意义。GMZB，颗粒酶B；Lef1，淋巴增强子结合因子1；Prf1，穿孔素1；Trem2，髓样细胞表达的触发受体2。 单细胞生物学的出现为理解人类生物过程以及诊断、监测和治疗疾病开启了新的篇章。这场革命如今延伸到了心血管疾病（CVD）领域。以单细胞分辨率研究心血管疾病样本的新技术使得识别在疾病发展过程中起重要作用的新型细胞群落成为可能，并指向新的治疗策略。这些方法已经开始革新动脉粥样硬化病理学，并重塑我们对疾病发展的理解。这篇综述讨论了动脉粥样硬化斑块单细胞分析的最新进展，特别关注人类病变，并介绍了细胞亚群的当前分辨率及其与临床相关特征相关的异质性和可塑性。强调了当前技术的机遇和缺陷以及单细胞技术在心血管疾病患者护理中的临床影响，倡导多学科和国际合作努力来连接心血管疾病的细胞点。