MELAS综合征患者的急性心肌梗死:可能的联系?

IF 1.4 4区 医学 Q3 CARDIAC & CARDIOVASCULAR SYSTEMS
Minerva cardiology and angiology Pub Date : 2023-08-01 Epub Date: 2022-06-29 DOI:10.23736/S2724-5683.22.06021-5
Joseph Cosma, Alessandro Russo, Sofia Schino, Martina Belli, Ruggiero Mango, Gaetano Chiricolo, Eugenio Martuscelli, Enrica G Mariano
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引用次数: 1

摘要

线粒体脑肌病、乳酸酸中毒和中风(MELAS)综合征是一种线粒体疾病,通常由MT-TL1基因m.3243A>G突变引起。它编码线粒体亮氨酸转移RNA (tRNA Leu [UUR]),涉及电子传递链中线粒体复合物组装和功能相关蛋白质的翻译。m.3243A>G突变决定复合物I (CI)缺乏,最终导致NADH积累,更高的糖酵解速率,以补偿减少的ATP产生和糖酵解的最终产物乳酸盐的增加。氧化磷酸化功能的破坏,不能产生足够的能量,导致多器官功能障碍,高能量需求的细胞,如肌细胞和神经元,是最受影响的。因此,MELAS综合征具有异质性的临床谱特征。在此,我们报告一例55岁男性MELA综合征,无心血管危险因素。他因非st段抬高型心肌梗死(NSTEMI)而入住我科。完成后降支和左前降支冠状动脉成形术。经胸超声心动图显示左室下壁和前壁运动不足并伴有中度左心室肥厚。据报道,约三分之一的患者心脏受累,左心室肥厚(LVH)是最常见的表型,终末期疾病可能伴有扩张型心肌病;brady-心律失常和速性心律失常以及Wolff- Parkinson-White (WPW)综合征也经常被报道。器官损害和临床表现取决于细胞中突变DNA的异质性水平,这在个体之间可能存在差异,这解释了为什么有些患者会出现更严重的疾病。MELAS综合征与动脉粥样硬化之间的明确关系从未建立,但最近提倡。MELAS患者的体外研究表明,由于复合物I缺乏和电子传递中断,线粒体ROS水平升高和氧化应激相关基因表达增加,使循环中的LDL迅速氧化为ox-LDL,导致内皮功能障碍和动脉粥样硬化斑块形成。鉴于最近的证据表明线粒体疾病与动脉粥样硬化之间可能存在联系,我们推测MELAS综合征可能在我们患者冠状动脉疾病的发病机制中发挥了作用。需要进一步调查以确认其致病关系。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Acute myocardial infarction in a patient with MELAS syndrome: a possible link?

The mitochondrial encephalomyopathy, lactic acidosis, and stroke (MELAS) syndrome is a mitochondrial disorder, commonly caused by m.3243A>G mutation in the MT-TL1 gene. It encodes for the mitochondrial leucine transfer RNA (tRNA Leu [UUR]), implicated in the translation of proteins involved in the assembly and function of mitochondrial complexes in the electron transport chain. The m.3243A>G mutation determines complex I (CI) deficiency, ultimately leading to NADH accumulation, higher rates of glycolysis in order to compensate for the reduced ATP production and increase in lactates, the end-product of glycolysis. Disruption of the oxidative phosphorylation function with an inability to produce sufficient energy results in multi-organ dysfunction, with high energy demanding cells, such as myocytes and neurons, being the most affected ones. Therefore, MELAS syndrome is characterized by a heterogeneous clinical spectrum. Here we report on a case of a 55-year-old man affected by MELA syndrome with no cardiovascular risk factors. He was admitted to our department because of a non ST-segment elevation myocardial infarction (NSTEMI). A coronary angioplasty of the posterior descending artery and of the left anterior descending artery was realized. Transthoracic echocardiography showed inferior and anterior left ventricular wall hypokinesis together with a moderate left ventricle hypertrophy. Cardiac involvement is reported in about a third of the patients and left ventricular hypertrophy (LVH) is the most common phenotype, with possible dilated cardiomyopathy in end-stage disease; brady- arrhythmias and tachy-arrhythmias are also frequently reported as well as Wolff- Parkinson-White (WPW) syndrome. Organ impairment and clinical manifestations depend on the heteroplasmy level of mutant DNA in cells that can differ among individuals, explaining why some patients present a more severe disease. A clear relationship between MELAS syndrome and atherosclerosis has never been established, however recently advocated. In vitro studies in MELAS patients have shown that higher mitochondrial ROS levels and increased expression of oxidative stress-related genes, as a consequence of complex I deficiency and disrupted electron transport, allow circulating LDL to be promptly oxidized into ox-LDL, contributing to endothelial dysfunction and atherosclerosis plaque formation. In light of the recent evidence suggesting a possible link between mitochondrial disorders and atherosclerosis, we speculate that MELAS syndrome may have played a role in the pathogenesis of coronary artery disease in our patient. Further investigations are needed to confirm a pathogenetic link.

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Minerva cardiology and angiology
Minerva cardiology and angiology CARDIAC & CARDIOVASCULAR SYSTEMS-
CiteScore
2.60
自引率
18.80%
发文量
118
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