Lorca Rebeca, Aparicio Andrea, Gómez Juan, Álvarez-Velasco Rut, Pascual Isaac, Avanzas Pablo, González-Urbistondo Francisco, Alen Alberto, Vázquez-Coto Daniel, González-Fernández Mar, García-Lago Claudia, Cuesta-Llavona Elías, Morís César, Coto Eliecer
Área del Corazón, Hospital Universitario Central Asturias, 33011 Oviedo, Spain.
Instituto de Investigación Sanitaria del Principado de Asturias, ISPA, 33011 Oviedo, Spain.
J Clin Med. 2023 Mar 8;12(6):2133. doi: 10.3390/jcm12062133.
Mitochondrial DNA (mtDNA) differs from the nuclear genome in many aspects: a maternal inheritance pattern; being more prone to acquire somatic de novo mutations, accumulative with age; and the possible coexistence of different mtDNA alleles (heteroplasmy). Mitochondria are key cellular organelles responsible for energy production and involved in complex mechanisms, including atherosclerosis. In this scenario, we aimed to evaluate mtDNA variants that could be associated with premature cardiovascular disease. We evaluated 188 consecutive patients presenting with premature myocardial infarction with ST elevation (STEMI) confirmed by coronary angiogram. mtDNA polymorphisms and clinical data were evaluated and compared with 271 individuals from the same population (control group). Tobacco consumption (80.85% vs. 21.21%, < 0.01) and dyslipidemia (38.83% vs. 28.41%, = 0.02) were significantly more frequent among STEMI patients. Moreover, C16223T mtDNA mutation and poly-C heteroplasmy were significantly more frequent among premature STEMI male patients than in controls. The OR associated C16223T mtDNA with the increased presence of cardiovascular risk factors. Our data suggest that mtDNA 16223T and heteroplasmy may be associated with unstable premature atherosclerosis disease in men. Moreover, the presence of cardiovascular risk factors (CVRFs) was associated with C16223T mtDNA, with a cumulative effect. Protective mitochondrial pathways are potential therapeutic targets. Preventing exposure to the damaging mechanisms associated with CVRFs is of utmost importance.
线粒体DNA（mtDNA）在许多方面不同于核基因组：母系遗传模式；更容易发生体细胞新生突变，且随着年龄增长而累积；以及可能存在不同的mtDNA等位基因（异质性）。线粒体是负责能量产生的关键细胞器，并参与包括动脉粥样硬化在内的复杂机制。在这种情况下，我们旨在评估可能与早发性心血管疾病相关的mtDNA变异。我们评估了188例经冠状动脉造影证实为ST段抬高型早发性心肌梗死（STEMI）的连续患者。对mtDNA多态性和临床数据进行了评估，并与来自同一人群的271名个体（对照组）进行了比较。STEMI患者中烟草消费（80.85%对21.21%，<0.01）和血脂异常（38.83%对28.41%，=0.02）的发生率明显更高。此外，早发性STEMI男性患者中C16223T mtDNA突变和多聚C异质性明显比对照组更常见。与C16223T mtDNA相关的比值比与心血管危险因素的增加存在有关。我们的数据表明，mtDNA 16223T和异质性可能与男性不稳定的早发性动脉粥样硬化疾病有关。此外，心血管危险因素（CVRFs）的存在与C16223T mtDNA相关，具有累积效应。保护性线粒体途径是潜在的治疗靶点。预防暴露于与CVRFs相关的损伤机制至关重要。
