Cardiac Complications of Propionic and Other Inherited Organic Acidemias.
Cardiac Complications of Propionic and Other Inherited Organic Acidemias.
复制标题
DOI：
10.3389/fcvm.2020.617451
复制
发表时间：
2020
影响因子：
3.6
通讯作者：
Swietach P
中科院分区：
文献类型：
--
作者：
Park KC;Krywawych S;Richard E;Desviat LR;Swietach P
临床观察和实验研究已经确定，全身性酸碱失衡可以深刻地影响心脏。关于pH值改变对心脏功能的影响有大量的信息，但相比之下，对酸中毒中与H+离子一起积累的有机阴离子的作用知之甚少。在血液和其他体液中，这些有机化学物质在严重的代谢性酸中毒中可以共同达到几毫摩尔的浓度，如在遗传性有机酸中毒的情况下，并对心脏产生强大的生物作用，这是无法直观预测的。事实上，心脏病理，如心肌病和心律失常，经常报告有机酸血症患者，但潜在的病理生理机制还没有很好地建立。近年来，有机阴离子生理学领域的研究工作急剧增加，特别是丙酸盐，丙酸盐在丙酸血症中积累，丙酸血症是最常见的有机酸血症之一，其特征在于心脏病的高发病率。本综述提供了一个全面的历史概述，所有已知的有机酸中毒的特点是心脏并发症和最先进的概述在丙酸血症中观察到的心脏后遗症。本文确定了与丙酸阴离子（及其代谢物）异常接合的分子机制的最有希望的候选者，并讨论了这些可能如何导致丙酸血症中的心脏紊乱。关键的临床和实验研究结果被认为是在不久的将来潜在的治疗方法的背景下。
Clinical observations and experimental studies have determined that systemic acid-base disturbances can profoundly affect the heart. A wealth of information is available on the effects of altered pH on cardiac function but, by comparison, much less is known about the actions of the organic anions that accumulate alongside H+ ions in acidosis. In the blood and other body fluids, these organic chemical species can collectively reach concentrations of several millimolar in severe metabolic acidoses, as in the case of inherited organic acidemias, and exert powerful biological actions on the heart that are not intuitive to predict. Indeed, cardiac pathologies, such as cardiomyopathy and arrhythmia, are frequently reported in organic acidemia patients, but the underlying pathophysiological mechanisms are not well established. Research efforts in the area of organic anion physiology have increased dramatically in recent years, particularly for propionate, which accumulates in propionic acidemia, one of the commonest organic acidemias characterized by a high incidence of cardiac disease. This Review provides a comprehensive historical overview of all known organic acidemias that feature cardiac complications and a state-of-the-art overview of the cardiac sequelae observed in propionic acidemia. The article identifies the most promising candidates for molecular mechanisms that become aberrantly engaged by propionate anions (and its metabolites), and discusses how these may result in cardiac derangements in propionic acidemia. Key clinical and experimental findings are considered in the context of potential therapies in the near future.
登录
查看更多内容
影响因子：
3.7
作者：
Clarke SL;Bowron A;Gonzalez IL;Groves SJ;Newbury-Ecob R;Clayton N;Martin RP;Tsai-Goodman B;Garratt V;Ashworth M;Bowen VM;McCurdy KR;Damin MK;Spencer CT;Toth MJ;Kelley RI;Steward CG
通讯作者：
Steward CG
影响因子：
5.1
作者：
Baumgartner, Daniela;Scholl-Buergi, Sabine;Karall, Daniela
通讯作者：
Karall, Daniela
影响因子：
4.2
作者：
Carrozzo, Rosalba;Verrigni, Daniela;Ostergaard, Elsebet
通讯作者：
Ostergaard, Elsebet
影响因子：
4.4
作者：
BARTH, PG;SCHOLTE, HR;SOBOTKAPLOJHAR, MA
通讯作者：
SOBOTKAPLOJHAR, MA
影响因子：
5.5
作者：
Bodi, Ilona;Gruenert, Sarah C.;Odening, Katja E.
通讯作者：
Odening, Katja E.