利用脫附式電噴灑游離質譜法進行氧化三甲胺快速定量之新式心血管疾病風險評估平台

Abstract

心血管疾病有著極高的盛行率以及逐年提升的死亡率，讓這類疾病成為了世界主要的健康問題之一。三甲基胺氧化物在近二十年內已經被確認是重要的心血管疾病風險因子之一。此分子一開始被發現參與進與腸道菌有關的膳食磷脂膽鹼代謝，並且被發現到會誘使動脈粥狀硬化發生，且與不良心血管疾病事件有關。然而常規化的三甲基胺氧化物之檢測在現今是具有難度的，其原因在於缺乏一個簡單、可靠、且高通量的定量平台。因此，我們開發了一個基於脫附式電噴灑游離質譜法的新穎定量平台，以用於快速的三甲基胺氧化物之分析，並對常規化的心血管疾病風險之預測做出貢獻。經過對樣品前處理方式、脫附式電噴灑游離儀以及質譜儀之運作參數進行最佳化後，此平台在具生物意義的濃度區間內表現出高度的精準度、準確度、以及再現性。在平台建立完成以後，此平台也被用以進行197個人類血漿樣品的分析以進行平台之確效。結果顯示，在定量實驗與風險等級分類上，此平台與傳統的液相層析串聯質譜法平台所得到的結果具有高度的一致性，同時將分析時間大幅縮短了十倍。透過使用此一快速、穩定、高通量的基於脫附式電噴灑游離法開發之三甲胺氧化物分析平台，常規化的心血管疾病風險評估將會成為可行的方案，並藉此對於個人化的醫療策略或是健康照護有所助益。

Cardiovascular disease (CVD) has emerged as a major global health concern due to its high prevalence and elevated mortality rates. A recognized risk factor for CVD is Trimethylamine N-oxide (TMAO), a metabolite derived from the gut-microbiome-linked metabolism of dietary choline, which has been implicated in promoting atherosclerosis and associated with adverse cardiovascular outcomes. Routine TMAO screening for CVD risk prediction, however, remains a challenge due to the lack of a well-validated strategy utilized in a simple and high-throughput manner. Here, we introduced a novel approach employing desorption electrospray ionization mass spectrometry (DESI-MS) for rapid plasma TMAO quantification to aid in widespread CVD risk assessment. The DESI-MS platform exhibited high accuracy, precision, and reproducibility after optimization of sample pretreatment and instrumental parameters. Next, the platform was validated by analyzing 197 plasma samples. The analysis results showed high consistency with those obtained from liquid chromatography-tandem mass spectrometry (LC-MS/MS) techniques while speeding up ten times. By adopting this rapid, robust, and high-throughput DESI-MS platform for TMAO analysis, routine CVD risk assessment could be achieved, thereby benefiting personalized treatment and healthcare strategies.