Department of Physiology, Institute for Cardiovascular Research, VU University Medical Center, O|2 Building, De Boelelaan 1118, Amsterdam 1081 HV, The Netherlands
Department of Physiology, Institute for Cardiovascular Research, VU University Medical Center, O|2 Building, De Boelelaan 1118, Amsterdam 1081 HV, The Netherlands.
Cardiovasc Res. 2016 Sep;111(4):362-72. doi: 10.1093/cvr/cvw176. Epub 2016 Jul 11.
In cardiac hypertrophy (CH) and heart failure (HF), alterations occur in mitochondrial enzyme content and activities but the origin and implications of these changes for mitochondrial function need to be resolved.
Right ventricular CH or HF was induced by monocrotaline injection, which causes pulmonary artery hypertension, in rats. Results were compared with saline injection (CON). NAD(P)H and FAD autofluorescence were recorded in thin intact cardiac trabeculae during transitions in stimulation frequency, to assess mitochondrial complex I and complex II function, respectively. Oxygen consumption, mitochondrial morphology, protein content, and enzymatic activity were assessed. NAD(P)H autofluorescence upon an increase in stimulation frequency showed a rapid decline followed by a slow recovery. FAD autofluorescence followed a similar time course, but in opposite direction. The amplitude of the early rapid change in NAD(P)H autofluorescence was severely depressed in CH and HF compared with CON. The rapid changes in FAD autofluorescence in CH and HF were reduced to a lesser extent. Complex I-coupled respiration showed an ∼3.5-fold reduction in CH and HF; complex II-coupled respiration was depressed two-fold in HF. Western blot analyses revealed modest reductions in complex I protein content in CH and HF and in complex I activity in supercomplexes in HF. Mitochondrial volume density was similar, but mitochondrial remodelling was evident from changes in ultrastructure and fusion/fission indices in CH and HF.
These results suggest that the alterations in mitochondrial function observed in right ventricular CH and HF can be mainly attributed to complex I dysfunction.
在心肌肥厚（CH）和心力衰竭（HF）中，线粒体酶含量和活性发生改变，但这些变化对线粒体功能的起源和意义仍需阐明。
通过向大鼠注射单硝酸异山梨酯诱导右心室 CH 或 HF，该方法会导致肺动脉高压。将结果与盐水注射（CON）进行比较。在刺激频率转换过程中，在薄的完整心脏横切术中记录 NAD(P)H 和 FAD 自发荧光，以分别评估线粒体复合物 I 和复合物 II 的功能。评估耗氧量、线粒体形态、蛋白质含量和酶活性。刺激频率增加时 NAD(P)H 自发荧光的快速变化幅度在 CH 和 HF 中与 CON 相比明显降低。FAD 自发荧光遵循相似的时间过程，但方向相反。CH 和 HF 中 NAD(P)H 自发荧光的早期快速变化幅度明显降低。CH 和 HF 中的 FAD 自发荧光快速变化幅度降低幅度较小。CH 和 HF 中的复合物 I 偶联呼吸减少了约 3.5 倍；HF 中的复合物 II 偶联呼吸减少了两倍。Western blot 分析显示 CH 和 HF 中复合物 I 蛋白含量略有降低，HF 中超复合物中的复合物 I 活性降低。线粒体体积密度相似，但 CH 和 HF 中的超微结构和融合/分裂指数的变化表明线粒体发生重塑。
这些结果表明，右心室 CH 和 HF 中观察到的线粒体功能改变主要归因于复合物 I 功能障碍。
