Li Wei, Luo Jichang, Peng Fangda, Liu Ruiting, Bai Xuesong, Wang Tao, Zhang Xiao, Zhu Junge, Li Xu-Ying, Wang Zhanjun, Liu Wubin, Wang Jiyue, Zhang Liyong, Chen Xianyang, Xue Teng, Ding Chunguang, Wang Chaodong, Jiao Liqun
Department of Stroke Center, Central Hospital Affiliated to Shandong First Medical University, China; Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China.
Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China.
Atherosclerosis. 2023 Jan;364:20-28. doi: 10.1016/j.atherosclerosis.2022.11.019. Epub 2022 Nov 24.
Carotid atherosclerosis is an important cause of ischemic stroke. Lipids play a key role in the progression of atherosclerosis. To date, the spatial lipid profile of carotid atherosclerotic plaques related to histology has not been systematically investigated.
Carotid atherosclerosis samples from 12 patients were obtained and classified into four classical pathological stages (preatheroma, atheroma, fibroatheroma and complicated lesion) by histological staining. Desorption electrospray ionization-mass spectrometry imaging (DESI-MSI) was used to investigate the lipid profile of carotid atherosclerosis, and correlated it with histological information. Bioinformatics technology was used to process MSI data among different pathological stages of atherosclerosis lesions.
A total of 55 lipids (26 throughout cross-section regions [TCSRs], 13 in lipid-rich regions [LRRs], and 16 in collagen-rich regions [CRRs]) were initially identified in carotid plaque from one patient. Subsequently, 32 of 55 lipids (12 in TCSRs, eight in LRRs, and 12 in CRRs) were further screened in 11 patients. Pathway enrichment analysis showed that multiple metabolic pathways, such as fat digestion and absorption, cholesterol metabolism, lipid and atherosclerosis, were enriched in TCSRs; sphingolipid signaling pathway, necroptosis pathway were enriched in LRRs; and glycerophospholipid metabolism, ether lipid metabolism pathway were mainly enriched in CRRs.
This study comprehensively showed the spatial lipid metabolism footprint in human carotid atherosclerotic plaques. The lipid profiles and related metabolism pathways in three regions of plaque with disease progression were different markedly, suggesting that the different metabolic mechanisms in these regions of carotid plaque may be critical in atherosclerosis progression.
颈动脉粥样硬化是缺血性中风的重要病因。脂质在动脉粥样硬化进展中起关键作用。迄今为止，与组织学相关的颈动脉粥样硬化斑块的空间脂质分布尚未得到系统研究。
获取12例患者的颈动脉粥样硬化样本，通过组织学染色将其分为四个经典病理阶段（脂质条纹前期、粥样斑块期、纤维粥样斑块期和复杂病变期）。采用解吸电喷雾电离质谱成像（DESI-MSI）研究颈动脉粥样硬化的脂质分布，并将其与组织学信息相关联。运用生物信息学技术处理动脉粥样硬化病变不同病理阶段的MSI数据。
在一名患者的颈动脉斑块中初步鉴定出总共55种脂质（26种在整个横截面区域 [TCSR]，13种在富含脂质区域 [LRR]，16种在富含胶原蛋白区域 [CRR]）。随后，在11例患者中对55种脂质中的32种（12种在TCSR，8种在LRR，12种在CRR）进行了进一步筛选。通路富集分析表明，多个代谢通路，如脂肪消化与吸收、胆固醇代谢、脂质与动脉粥样硬化，在TCSR中富集；鞘脂信号通路、坏死性凋亡通路在LRR中富集；甘油磷脂代谢、醚脂代谢通路主要在CRR中富集。
本研究全面展示了人类颈动脉粥样硬化斑块中的空间脂质代谢印记。随着疾病进展，斑块三个区域的脂质分布及相关代谢通路存在显著差异，提示颈动脉斑块这些区域不同的代谢机制可能在动脉粥样硬化进展中起关键作用。
