Mołek Patrycja, Żmudzki Paweł, Machnik Andrzej, Nowak Grażyna, Stępień Konrad, Wnuk Mateusz, Włodarczyk Aleksandra, Nowak Karol, Rychlak Radosław, Nessler Jadwiga, Zalewski Jarosław
Department of Coronary Disease and Heart Failure, Jagiellonian University Medical College, Kraków, Poland
Clinical Department of Coronary Disease and Heart Failure, John Paul II Hospital, Kraków, Poland
Pol Arch Intern Med. 2023 Feb 27;133(2). doi: 10.20452/pamw.16356. Epub 2022 Oct 13.
Arginase inhibition increases plasma citrulline and citrulline / ornithine (C/O) ratio, and reduces plasma ornithine and ornithine / arginine (O/A) ratio in an animal model of myocardial infarction (MI).
We hypothesized that the presence of thin‑cap fibroatheroma (TCFA) in the culprit lesion and increased non‑culprit intima‑media thickness of an infarct‑related artery (IRA) are associated with an altered balance of arginine metabolites.
Arginine and its metabolites were measured using liquid chromatography and tandem mass spectrometry in 100 consecutive MI patients upon admission and at 6‑month follow‑up. TCFA and adjacent to culprit lesion proximal and distal 10‑mm segments were assessed with optical coherence tomography in the acute phase. Twenty five patients without coronary lesions on angiography served as controls.
The C/O ratio increased 5.33 times (P <0.001), while the O/A ratio decreased 2.53 times (P <0.001) at the 6‑month follow‑up, as compared with the acute phase of MI. The patients with (n = 75) vs without (n = 25) TCFA had lower C/O ratio by 29% (P = 0.003), while the mean intima‑media diameter of adjacent non‑culprit region correlated with the follow‑up O/A ratio (R = 0.337; P = 0.003). In a multivariable analysis, a higher acute phase C/O ratio was associated with a lower risk of TCFA presence (odds ratio, 0.978; 95% CI, 0.962-0.994; P = 0.006), whereas a higher follow‑up O/A ratio correlated with larger intima‑media diameter of the adjacent segments (β coefficient, 0.227; 95% CI for β coefficient, 0.045-0.409; P = 0.018).
Enhanced arginase activity over nitric oxide synthase following ischemia was associated with the presence of TCFA in the culprit lesion, while a similar metabolic shift in the chronic phase correlated with a greater thickness of the intima‑media in the adjacent non‑culprit IRA segments.
在心肌梗死（MI）动物模型中，抑制精氨酸酶可增加血浆瓜氨酸及瓜氨酸/鸟氨酸（C/O）比值，并降低血浆鸟氨酸及鸟氨酸/精氨酸（O/A）比值。
我们假设罪犯病变中薄帽纤维粥样斑块（TCFA）的存在以及梗死相关动脉（IRA）非罪犯部位内膜中层厚度增加与精氨酸代谢产物平衡改变有关。
采用液相色谱和串联质谱法对100例连续入选的MI患者入院时及随访6个月时的精氨酸及其代谢产物进行检测。急性期采用光学相干断层扫描评估TCFA及罪犯病变近端和远端10毫米节段。25例血管造影无冠状动脉病变的患者作为对照。
与MI急性期相比，随访6个月时C/O比值增加5.33倍（P<0.001），而O/A比值降低2.53倍（P<0.001）。有TCFA（n = 75）与无TCFA（n = 25）的患者相比，C/O比值低29%（P = 0.003），而相邻非罪犯区域的平均内膜中层直径与随访O/A比值相关（R = 0.337；P = 0.003）。在多变量分析中，急性期较高的C/O比值与TCFA存在风险较低相关（比值比，0.978；95%CI，0.962 - 0.994；P = 0.006），而随访时较高的O/A比值与相邻节段较大的内膜中层直径相关（β系数，0.227；β系数的95%CI，0.045 - 0.409；P = 0.018）。
缺血后精氨酸酶活性高于一氧化氮合酶与罪犯病变中TCFA的存在有关，而慢性期类似的代谢变化与相邻非罪犯IRA节段内膜中层厚度增加有关。
