Vilella-Figuerola Alba, Padró Teresa, Roig Eulàlia, Mirabet Sònia, Badimon Lina
Cardiovascular-Program ICCC, IR-Hospital Santa Creu i Sant Pau, IIB-Sant Pau, Barcelona, Spain.
Department of Biochemical and Molecular Biology, Universitat Autònoma de Barcelona, Barcelona, Spain.
Front Cardiovasc Med. 2022 Nov 3;9:939625. doi: 10.3389/fcvm.2022.939625. eCollection 2022.
Leukocyte-shed extracellular vesicles (EVs) can play effector roles in the pathophysiological mechanisms of different diseases. These EVs released by membrane budding of leukocytes have been found in high amounts locally in inflamed tissues and in the circulation, indicating immunity cell activation. These EVs secreted by immune cell subsets have been minimally explored and deserve further investigation in many areas of disease. In this study we have investigated whether in heart failure there is innate and adaptive immune cell release of EVs. Patients with chronic heart failure (cHF) ( = 119) and in sex- and age-matched controls without this chronic condition ( = 60). Specifically, EVs were quantified and phenotypically characterized by flow cytometry and cell-specific monoclonal antibodies. We observed that even in well medically controlled cHF patients (with guideline-directed medical therapy) there are higher number of blood annexin-V (phosphatidylserine)-EVs carrying activated immunity cell-epitopes in the circulation than in controls ( < 0.04 for all cell types). Particularly, EVs shed by monocytes and neutrophils (innate immunity) and by T-lymphocytes and natural-killer cells (adaptive immunity) are significantly higher in cHF patients. Additionally, EVs-shed by activated leukocytes/neutrophils (CD11b, = 0.006; CD29/CD15, = 0.048), and T-lymphocytes (CD3/CD45, < 0.02) were positively correlated with cHF disease severity (NYHA classification). Interestingly, cHF patients with ischemic etiology had the highest levels of EVs shed by lymphocytes and neutrophils ( < 0.045, all). In summary, in cHF patients there is a significant immune cell activation shown by high-release of EVs that is accentuated by clinical severity of cHF. These activated innate and adaptive immunity cell messengers may contribute by intercellular communication to the progression of the disease and to the common affectation of distant organs in heart failure (paracrine regulation) that contribute to the clinical deterioration of cHF patients.
白细胞脱落的细胞外囊泡（EVs）可在不同疾病的病理生理机制中发挥效应作用。这些通过白细胞膜出芽释放的EVs已在炎症组织局部和循环中大量发现，表明免疫细胞被激活。免疫细胞亚群分泌的这些EVs在许多疾病领域的研究还很少，值得进一步探究。在本研究中，我们调查了心力衰竭患者是否存在固有免疫和适应性免疫细胞释放EVs的情况。纳入慢性心力衰竭（cHF）患者（n = 119）以及年龄和性别匹配的无此慢性疾病的对照组（n = 60）。具体而言，通过流式细胞术和细胞特异性单克隆抗体对EVs进行定量和表型特征分析。我们观察到，即使在药物控制良好的cHF患者（接受指南指导的药物治疗）中，循环中携带活化免疫细胞表位的血膜联蛋白-V（磷脂酰丝氨酸）-EVs数量也高于对照组（所有细胞类型P < 0.04）。特别是，cHF患者中单核细胞和中性粒细胞（固有免疫）以及T淋巴细胞和自然杀伤细胞（适应性免疫）脱落的EVs显著更高。此外，活化白细胞/中性粒细胞（CD11b，P = 0.006；CD29/CD15，P = 0.048）和T淋巴细胞（CD3/CD45，P < 0.02）脱落的EVs与cHF疾病严重程度（NYHA分级）呈正相关。有趣的是，缺血性病因的cHF患者淋巴细胞和中性粒细胞脱落的EVs水平最高（所有P < 0.045）。总之，在cHF患者中，EVs的高释放表明存在显著的免疫细胞激活，且cHF的临床严重程度会加剧这种激活。这些活化的固有免疫和适应性免疫细胞信使可能通过细胞间通讯促进疾病进展以及心力衰竭中远处器官共同受累（旁分泌调节），从而导致cHF患者临床病情恶化。
