Gawryś-Kopczyńska Marta, Szudzik Mateusz, Samborowska Emilia, Konop Marek, Chabowski Dawid, Onyszkiewicz Maksymilian, Ufnal Marcin
Department of Experimental Physiology and Pathophysiology, Laboratory of Centre for Preclinical Research, Medical University of Warsaw, Warsaw, Poland.
Mass Spectrometry Laboratory, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland.
Front Physiol. 2024 Apr 12;15:1340166. doi: 10.3389/fphys.2024.1340166. eCollection 2024.
Flavin monooxygenases (FMOs) are enzymes responsible for the oxidation of a broad spectrum of exogenous and endogenous amines. There is increasing evidence that trimethylamine (TMA), a compound produced by gut bacteria and also recognized as an industrial pollutant, contributes to cardiovascular diseases. FMOs convert TMA into trimethylamine oxide (TMAO), which is an emerging marker of cardiovascular risk. This study hypothesized that blood pressure phenotypes in rats might be associated with variations in the expression of FMOs. The expression of FMO1, FMO3, and FMO5 was evaluated in the kidneys, liver, lungs, small intestine, and large intestine of normotensive male Wistar-Kyoto rats (WKY) and two distinct hypertensive rat models: spontaneously hypertensive rats (SHRs) and WKY rats with angiotensin II-induced hypertension (WKY-ANG). Plasma concentrations of TMA and TMAO were measured at baseline and after intravenous administration of TMA using liquid chromatography-mass spectrometry (LC-MS). We found that the expression of FMOs in WKY, SHR, and WKY-ANG rats was in the descending order of FMO3 > FMO1 >> FMO5. The highest expression of FMOs was observed in the liver. Notably, SHRs exhibited a significantly elevated expression of FMO3 in the liver compared to WKY and WKY-ANG rats. Additionally, the plasma TMAO/TMA ratio was significantly higher in SHRs than in WKY rats. SHRs demonstrate enhanced expression of FMO3 and a higher plasma TMAO/TMA ratio. The variability in the expression of FMOs and the metabolism of amines might contribute to the hypertensive phenotype observed in SHRs.
黄素单加氧酶(FMOs)是负责氧化多种外源性和内源性胺类的酶。越来越多的证据表明,三甲胺(TMA)这种由肠道细菌产生且也被视为工业污染物的化合物,会导致心血管疾病。FMOs将TMA转化为氧化三甲胺(TMAO),而TMAO是一种新出现的心血管风险标志物。本研究假设大鼠的血压表型可能与FMOs表达的变化有关。在正常血压的雄性Wistar-Kyoto大鼠(WKY)以及两种不同的高血压大鼠模型:自发性高血压大鼠(SHRs)和血管紧张素II诱导高血压的WKY大鼠(WKY-ANG)的肾脏、肝脏、肺、小肠和大肠中评估了FMO1、FMO3和FMO5的表达。使用液相色谱-质谱联用(LC-MS)在基线时以及静脉注射TMA后测量血浆中TMA和TMAO的浓度。我们发现,WKY、SHR和WKY-ANG大鼠中FMOs的表达顺序为FMO3>FMO1>>FMO5。FMOs在肝脏中的表达最高。值得注意的是,与WKY和WKY-ANG大鼠相比,SHRs肝脏中FMO3的表达显著升高。此外,SHRs的血浆TMAO/TMA比值显著高于WKY大鼠。SHRs表现出FMO3表达增强以及血浆TMAO/TMA比值更高。FMOs表达的变异性和胺类代谢可能导致SHRs中观察到的高血压表型。