Matan Dmitri, Mobarrez Fariborz, Löfström Ulrika, Corbascio Matthias, Ekström Mattias, Hage Camilla, Lyngå Patrik, Persson Bengt, Eriksson Maria, Linde Cecilia, Persson Hans, Wallén Håkan
Division of Cardiovascular Medicine, Department of Clinical Sciences, Karolinska Institutet, Danderyd University Hospital, Stockholm, Sweden.
Heart and Vascular Theme, Karolinska University Hospital, Stockholm, Sweden.
Front Cardiovasc Med. 2022 Oct 18;9:952974. doi: 10.3389/fcvm.2022.952974. eCollection 2022.
Extracellular vesicles (EVs) were investigated as potential biomarkers associated with heart failure (HF) pathophysiology in patients undergoing elective coronary artery bypass surgery characterized by HF phenotype.
Patients with preoperative proxy-diagnoses of HF types i.e., preserved (HFpEF; = 19) or reduced ejection fraction (HFrEF; = 20) were studied and compared to patients with normal left ventricular function ( = 42). EVs in plasma samples collected from the coronary sinus, an arterial line, and from the right atrium were analyzed by flow cytometry. We studied EVs of presumed cardiomyocyte origin [EVs exposing Connexin-43 + Caveolin-3 (Con43 + Cav3) and Connexin-43 + Troponin T (Con43 + TnT)], of endothelial origin [EVs exposing VE-Cadherin (VE-Cad)] and EVs exposing inflammatory markers [myeloperoxidase (MPO) or pentraxin3 (PTX3)].
Median concentrations of EVs exposing Con43 + TnT and Con43 + Cav3 were approximately five to six times higher in coronary sinus compared to radial artery indicative of cardiac release. Patients with HFrEF had high -coronary gradients of both Con43 + TnT and Con43 + Cav3 EVs, whereas HFpEF had elevated gradients of Con43 + Cav3 EVs but lower gradients of Con43 + TnT. Coronary sinus concentrations of both Con43 + TnT and Con43 + Cav3 correlated significantly with echocardiographic and laboratory measures of HF. MPO-EV concentrations were around two times higher in the right atrium compared to the coronary sinus, and slightly higher in HFpEF than in HFrEF. EV concentrations of endothelial origin (VE-Cad) were similar in all three patient groups.
Con43 + TnT and Con43 + Cav3 EVs are released over the heart indicating cardiomyocyte origin. In HFrEF the EV release profile is indicative of myocardial injury and myocardial stress with elevated -coronary gradients of both Con43 + TnT and Con43 + Cav3 EVs, whereas in HFpEF the profile indicates myocardial stress with less myocardial injury.
在以心力衰竭（HF）为表型的择期冠状动脉搭桥手术患者中，研究细胞外囊泡（EVs）作为与HF病理生理学相关的潜在生物标志物。
对术前初步诊断为HF类型（即射血分数保留的HF，HFpEF；n = 19）或射血分数降低的HF（HFrEF；n = 20）的患者进行研究，并与左心室功能正常的患者（n = 42）进行比较。通过流式细胞术分析从冠状窦、动脉管路和右心房采集的血浆样本中的EVs。我们研究了推测源自心肌细胞的EVs [暴露连接蛋白43 + 小窝蛋白3（Con43 + Cav3）和连接蛋白43 + 肌钙蛋白T（Con43 + TnT）的EVs]、源自内皮细胞的EVs [暴露血管内皮钙黏蛋白（VE-Cad）的EVs]以及暴露炎症标志物的EVs [髓过氧化物酶（MPO）或五聚素3（PTX3）]。
与桡动脉相比，冠状窦中暴露Con43 + TnT和Con43 + Cav3的EVs的中位浓度高出约五到六倍，表明是心脏释放。HFrEF患者的Con43 + TnT和Con43 + Cav3 EVs的冠状窦 - 动脉梯度均较高，而HFpEF患者Con43 + Cav3 EVs的梯度升高，但Con43 + TnT的梯度较低。冠状窦中Con43 + TnT和Con43 + Cav3的浓度均与HF的超声心动图和实验室指标显著相关。右心房中MPO - EV的浓度比冠状窦高约两倍，且在HFpEF中略高于HFrEF。所有三个患者组中源自内皮细胞的EVs（VE-Cad）浓度相似。
Con43 + TnT和Con43 + Cav3 EVs从心脏释放，表明源自心肌细胞。在HFrEF中，EV释放情况表明心肌损伤和心肌应激，Con43 + TnT和Con43 + Cav3 EVs的冠状窦 - 动脉梯度均升高，而在HFpEF中，这种情况表明心肌应激但心肌损伤较轻。
