Acute myocardial infarction (MI) is a cardiovascular disease that remains a major cause of morbidity and mortality worldwide despite advances in its prevention and treatment. During acute myocardial ischemia, the lack of oxygen switches the cell metabolism to anaerobic respiration, with lactate accumulation, ATP depletion, Na+ and Ca2+ overload, and inhibition of myocardial contractile function, which drastically modifies the lipid, protein, and small metabolite profile in the myocardium. Imaging mass spectrometry (IMS) is a powerful technique to comprehensively elucidate the spatial distribution patterns of lipids, peptides, and proteins in biological tissue sections. In this work, we demonstrate an application of multimodal chemical imaging using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS), which provided comprehensive molecular information in situ within the same mouse heart tissue sections with myocardial infarction. MALDI-IMS (at 30 μm per pixel) revealed infarct-associated spatial alterations of several lipid species of sphingolipids, glycerophospholipids, lysophospholipids, and cardiolipins along with the acyl carnitines. Further, we performed multimodal MALDI-IMS (IMS3) where dual polarity lipid imaging was combined with subsequent protein MALDI-IMS analysis (at 30 μm per pixel) within the same tissue sections, which revealed accumulations of core histone proteins H4, H2A, and H2B along with post-translational modification products, acetylated H4 and H2A, on the borders of the infarcted region. This methodology allowed us to interpret the lipid and protein molecular pathology of the very same infarcted region in a mouse model of myocardial infarction. Therefore, the presented data highlight the potential of multimodal MALDI imaging mass spectrometry of the same tissue sections as a powerful approach for simultaneous investigation of spatial infarct-associated lipid and protein changes of myocardial infarction.

中文翻译：

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多模态 MALDI 成像质谱揭示了急性心肌梗塞小鼠心脏的空间相关脂质和蛋白质变化。

急性心肌梗死 (MI) 是一种心血管疾病，尽管其预防和治疗取得了进展，但它仍然是全世界发病率和死亡率的主要原因。在急性心肌缺血期间，缺氧将细胞代谢转变为无氧呼吸，导致乳酸积累、ATP 消耗、Na+ 和 Ca2+ 超载以及心肌收缩功能受到抑制，这极大地改变了心肌中的脂质、蛋白质和小代谢物谱。心肌。成像质谱 (IMS) 是一种强大的技术，可以全面阐明生物组织切片中脂质、肽和蛋白质的空间分布模式。在这项工作中，我们展示了使用基质辅助激光解吸/电离质谱 (MALDI-MS) 的多模态化学成像的应用，它提供了与心肌梗塞相同的小鼠心脏组织切片中的原位综合分子信息。MALDI-IMS（每像素 30 μm）揭示了鞘脂、甘油磷脂、溶血磷脂和心磷脂以及酰基肉碱的几种脂质种类的梗塞相关空间改变。此外，我们进行了多模态 MALDI-IMS (IMS3)，其中双极性脂质成像与随后的蛋白质 MALDI-IMS 分析（每像素 30 μm）在相同的组织切片中相结合，揭示了核心组蛋白 H4、H2A 和H2B 连同翻译后修饰产物乙酰化 H4 和 H2A，位于梗塞区域的边界。这种方法使我们能够解释心肌梗塞小鼠模型中相同梗塞区域的脂质和蛋白质分子病理学。因此，所提供的数据突出了相同组织切片的多模态 MALDI 成像质谱作为同时研究心肌梗塞的空间梗塞相关脂质和蛋白质变化的强大方法的潜力。