Antibody-Mediated Imbalance of Myocardial Energy Metabolism

Author:

Schultheiß Heinz-Peter1,Schulze Karsten1,Schauer Rolf1,Witzenbichler Bernhard1,Strauer Bodo Eckehard1

Affiliation:

1. From Medizinische Klinik B, Heinrich-Heine Universität, Düsseldorf, Germany.

Abstract

Abstract The ADP-ATP carrier of the inner mitochondrial membrane is an autoantigen in myocarditis and dilated cardiomyopathy. Sera of patients with these diseases contain carrier-specific autoantibodies that inhibit the transmembrane nucleotide transport on isolated mitochondria. Guinea pigs immunized with the isolated ADP-ATP carrier protein also generate specific carrier-inactivating antibodies. In this study, we measured the cardiac function of guinea pigs immunized with the ADP-ATP carrier by determining the external heart work (EHW) of their isolated perfused spontaneously beating hearts stimulated by 4.0 mmol/L calcium and aortic ligature. Further, the electrogenic transport activity of the ADP-ATP carrier was estimated by calculating the cytosolic-mitochondrial difference of the phosphorylation potential of ATP [ΔG(cyt-mit)] in the freeze-clamped isolated hearts by nonaqueous fractionation. The EHW of immunized guinea pigs was seen to be reduced by 54% ( P <.005) compared with nonimmunized control guinea pigs, and ΔG(cyt-mit) declined from 4.9 kJ/mol ATP in nonimmunized control hearts to 2.3 kJ/mol ATP in the hearts of the immunized guinea pigs ( P <.005). The decisive result of this study, however, is the close relation observed between the magnitude of reduction of ΔG(cyt-mit) and the size of the decrease in EHW ( r =.87). Therefore, it seems plausible that antibody-mediated carrier dysfunction (creating the observed imbalance in myocardial energy metabolism) is responsible for the impairment of cardiac function. Our data support the hypothesis that immunopathic mechanisms in myocarditis and dilated cardiomyopathy can trigger subsequent heart failure. The underlying pathophysiological reason seems to be a metabolic disorder initiated by the antibody-mediated inactivation of the ADP-ATP carrier.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Cardiology and Cardiovascular Medicine,Physiology

Reference35 articles.

1. MYOCARDITIS AND DILATED CARDIOMYOPATHY

2. Myocarditis and cardiomyopathy

3. McManus BM Gauntt CJ Cassling RS. Immunopathologic basis of myocardial injury. In: Waller BF ed. Contemporary Issues in Cardiovascular Pathology—Cardiovasular Clinics . Philadelphia Pa: FA Davis Co; 1988:18/2:163-184.

Cited by 44 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3