原发性二尖瓣反流（PMR）与氧化和炎症性心肌损伤相关。我们报告了心包液（PCF）中外泌体血红蛋白（Hb）较血浆更多，表明Hb可能是心脏产生的。检验假设Hb在PMR心脏中产生，并与增加的炎症有关。通过对供体心脏（n = 10）和PMR患者手术活检（n = 11）的右心房（RA）、左心房（LA）和左心室（LV）组织进行Hb亚基α（HBA）和β（HBB）的基因表达评估。PMR患者（n = 22）采集了PCF和血液进行巨噬细胞标志物、促炎细胞因子和基质金属蛋白酶（MMPs）的检测。对PMR组织进行HBA mRNA的原位杂交和Hbα和Hbβ蛋白的免疫组织化学染色。RA、LA和LV的HBA和HBB基因在PMR与正常心脏相比均显著增加（>4倍）。在PMR组织中，通过原位杂交可见HBA mRNA在LV心肌细胞和间质细胞中表达，然而，通过免疫组织化学染色只有间质细胞表达Hbα和Hbβ蛋白。PCF中的氧Hb显著增加，同时出现低比例的血红蛋白：氧Hb和血红素：血红蛋白素的情况，支持存在高度氧化环境。与血浆相比，PCF中的巨噬细胞趋化蛋白1、肿瘤坏死因子-α、白细胞介素-6和MMPs均显著升高。PMR心脏中的Hb产生增加，结合心脏炎症状态，表明心肌在心脏手术期间可能对进一步的Hb释放和/或产生敏感，从而对LV功能恢复产生不利影响。© 2023版权所有。Elsevier Inc.出版。

Primary mitral regurgitation (PMR) is associated with oxidative and inflammatory myocardial damage. We reported greater exosome hemoglobin (Hb) in pericardial fluid (PCF) versus plasma, suggesting a cardiac source of Hb.Test the hypothesis that Hb is produced in the PMR heart and is associated with increased inflammation.Hb gene expression for subunits alpha (HBA) and beta (HBB) was assessed in right atria (RA), left atria (LA) and left ventricular (LV) tissue from donor hearts (n = 10) and PMR patients biopsies at surgery (n = 11). PMR patients (n = 22) had PCF and blood collected for macrophage markers, pro-inflammatory cytokines, and matrix metalloproteinases (MMPs). In-situ hybridization for HBA mRNA and immunohistochemistry for Hb-alpha (Hbα) and Hb-beta (Hbβ) protein was performed on PMR tissue.HBA and HBB genes are significantly increased (>4-fold) in RA, LA, and LV in PMR vs. normal hearts. In PMR tissue, HBA mRNA is expressed in both LV cardiomyocytes and interstitial cells by in-situ hybridization; however, Hbα and Hbβ protein is only expressed in interstitial cells by immunohistochemistry. PCF oxyHb is significantly increased over plasma along with low ratios (<1.0) of haptoglobin:oxyHb and hemopexin:heme supporting a highly oxidative environment. Macrophage chemotactic protein-1, tumor necrosis factor-α, interleukin-6, and MMPs are significantly higher in PCF vs. plasma.There is increased Hb production in the PMR heart coupled with the inflammatory state of the heart, suggests a myocardial vulnerability of further Hb delivery and/or production during cardiac surgery that could adversely affect LV functional recovery.Copyright © 2023. Published by Elsevier Inc.