Kindo Michel, Gerelli Sébastien, Bouitbir Jamal, Charles Anne-Laure, Zoll Joffrey, Hoang Minh Tam, Monassier Laurent, Favret Fabrice, Piquard François, Geny Bernard
Service de Chirurgie Cardiovasculaire, Pôle d'activité médico-chirurgicale Cardiovasculaire, Hôpitaux Universitaires, CHRU Strasbourg Strasbourg, France.
Front Physiol. 2012 Aug 28;3:332. doi: 10.3389/fphys.2012.00332. eCollection 2012.
Increased mechanical stress and contractility characterizes normal left ventricular (LV) subendocardium (Endo) but whether Endo mitochondrial respiratory chain complex activities is reduced as compared to subepicardium (Epi) and whether pressure overload-induced LV hypertrophy (LVH) might modulate transmural gradients through increased reactive oxygen species (ROS) production is unknown.
LVH was induced by 6 weeks abdominal aortic banding and cardiac structure and function were determined with echocardiography and catheterization in sham-operated and LVH rats (n = 10 for each group). Mitochondrial respiration rates, coupling, content and ROS production were measured in LV Endo and Epi, using saponin-permeabilized fibers, Amplex Red fluorescence and citrate synthase activity.
In sham, a transmural respiratory gradient was observed with decreases in endo maximal oxidative capacity (-36.7%, P < 0.01) and complex IV activity (-57.4%, P < 0.05). Mitochondrial hydrogen peroxide (H(2)O(2)) production was similar in both LV layers. Aortic banding induced mild LVH (+31.7% LV mass), associated with normal LV fractional shortening and end diastolic pressure. LVH reduced maximal oxidative capacity (-23.6 and -33.3%), increased mitochondrial H(2)O(2) production (+86.9 and +73.1%), free radical leak (+27.2% and +36.3%) and citrate synthase activity (+27.2% and +36.3%) in Endo and Epi, respectively. Transmural mitochondrial respiratory chain complex IV activity was reduced in LVH (-57.4 vs. -12.2%; P = 0.02).
Endo mitochondrial respiratory chain complexes activities are reduced compared to LV Epi. Mild LVH impairs mitochondrial oxidative capacity, increases oxidative stress and reduces transmural complex IV activity. Further studies will be helpful to determine whether reduced LV transmural gradient in mitochondrial respiration might be a new marker of a transition from uncomplicated toward complicated LVH.
机械应力增加和收缩性增强是正常左心室（LV）心内膜下层（Endo）的特征，但与心外膜下层（Epi）相比，Endo线粒体呼吸链复合体活性是否降低，以及压力超负荷诱导的左心室肥厚（LVH）是否可能通过增加活性氧（ROS）生成来调节跨壁梯度，目前尚不清楚。
通过6周腹主动脉缩窄诱导LVH，在假手术组和LVH大鼠（每组n = 10）中用超声心动图和导管插入术测定心脏结构和功能。使用皂素通透纤维、Amplex Red荧光和柠檬酸合酶活性测定LV Endo和Epi中的线粒体呼吸速率、偶联、含量和ROS生成。
在假手术组中，观察到跨壁呼吸梯度，Endo最大氧化能力降低（-36.7%，P < 0.01），复合体IV活性降低（-57.4%，P < 0.05）。两个LV层中的线粒体过氧化氢（H₂O₂）生成相似。主动脉缩窄诱导轻度LVH（LV质量增加31.7%），伴有正常的LV缩短分数和舒张末期压力。LVH分别降低了Endo和Epi中的最大氧化能力（-23.6%和-33.3%），增加了线粒体H₂O₂生成（+86.9%和+73.1%）、自由基泄漏（+27.2%和+36.3%）和柠檬酸合酶活性（+27.2%和+36.3%）。LVH中跨壁线粒体呼吸链复合体IV活性降低（-57.4%对-12.2%；P = 0.02）。
与LV Epi相比，Endo线粒体呼吸链复合体活性降低。轻度LVH损害线粒体氧化能力，增加氧化应激并降低跨壁复合体IV活性。进一步的研究将有助于确定LV线粒体呼吸中跨壁梯度降低是否可能是从单纯性LVH向复杂性LVH转变的新标志物。
