Department of Clinical Medicine, Health, Aarhus University, Aarhus, Denmark; Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark.
Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark.
J Heart Lung Transplant. 2022 Jun;41(6):732-741. doi: 10.1016/j.healun.2022.01.1376. Epub 2022 Feb 3.
Cardiac allograft vasculopathy (CAV) remains the Achilles' heel of long-term survival of HTx patients. Mitochondrial dysfunction has been reported in both arteriosclerotic coronary disease and heart failure. However, myocardial mitochondrial function has not been examined in HTx patients with CAV.
43 HTx patients (21 patients with CAV and 22 patients without CAV) ≥12 months after HTx were enrolled. Endomyocardial biopsies were analyzed using high-resolution respirometry for glucose-coupled mitochondrial respiration. Number and area of mitochondria profiles as well as cristae morphology were assessed by transmission electron microscopy. Echocardiography and coronary angiography were used to measure global longitudinal strain (GLS) and grade CAV.
Complex I+II-linked respiration was reduced in patients with CAV compared with patients without CAV (82.7 ± 31.9 pmol O2/(s•mg) vs 116 ± 35.9 pmol O2/(s•mg), p = 0.003). Mitochondrial respiratory function measured as oxidative phosphorylation coupling efficiency was positively associated with left ventricular GLS (r = 0.49, p = 0.002) and negatively associated with elevated biomarkers (Troponin T: r=-0.33, p = 0.04 and NT-proBNP: r = -0.41, p = 0.009). Mitochondrial profile number and area did not differ. However, patients with CAV had a larger proportion of mitochondria with abnormal cristae morphology (p < 0.001).
Myocardial mitochondrial respiration is impaired in patients with CAV and is associated with an abnormal cristae morphology. The mitochondrial dysfunction appears to be associated with reduced myocardial contractile function and elevated biomarkers. These results highlight that mitochondrial targeted treatment in patients with CAV should be assessed in future clinical studies.
心脏同种异体移植血管病（CAV）仍然是 HTx 患者长期存活的阿喀琉斯之踵。线粒体功能障碍已在动脉粥样硬化性冠状动脉疾病和心力衰竭中得到报道。然而，HTx 患者的 CAV 并未检查心肌线粒体功能。
纳入 43 名 HTx 患者（21 名 CAV 患者和 22 名无 CAV 患者），HTx 后≥12 个月。使用高分辨率呼吸测定法分析心肌活检，以评估葡萄糖偶联的线粒体呼吸。通过透射电子显微镜评估线粒体轮廓的数量和面积以及嵴形态。使用超声心动图和冠状动脉造影测量整体纵向应变（GLS）和 CAV 分级。
与无 CAV 患者相比，CAV 患者的复合物 I+II 连接呼吸减少（82.7 ± 31.9 pmol O2/（s•mg）与 116 ± 35.9 pmol O2/（s•mg），p = 0.003）。作为氧化磷酸化偶联效率测量的线粒体呼吸功能与左心室 GLS 呈正相关（r = 0.49，p = 0.002），与升高的生物标志物呈负相关（肌钙蛋白 T：r =-0.33，p = 0.04 和 NT-proBNP：r =-0.41，p = 0.009）。线粒体轮廓的数量和面积没有差异。然而，CAV 患者的异常嵴形态的线粒体比例更大（p < 0.001）。
CAV 患者的心肌线粒体呼吸受损，与异常嵴形态有关。线粒体功能障碍似乎与心肌收缩功能降低和生物标志物升高有关。这些结果强调，在未来的临床研究中应评估 CAV 患者的靶向线粒体治疗。
