Halade Ganesh V, Kain Vasundhara, Dillion Chrisly, Beasley Mark, Dudenbostel Tanja, Oparil Suzanne, Limdi Nita A
Division of Cardiovascular Sciences, Department of Medicine, University of South Florida, Tampa, FL, 33602, USA.
Department of Neurology, University of Alabama at Birmingham, Birmingham, AL, 35294, USA.
ESC Heart Fail. 2020 Aug;7(4):1700-1710. doi: 10.1002/ehf2.12730. Epub 2020 May 4.
Leucocyte-directed specialized pro-resolving mediators (SPMs) are essential for cardiac repair, and their biosynthesis coincides with the expression of pro-inflammatory mediators; however, the precise quantitation during an acute myocardial infarction (MI) event is poorly understood in race-specific and sex-specific manner. Coronary heart disease is the leading cause of death and disability in the USA. Although the prevalence of coronary heart disease is similar between Black and White patients, cardiovascular events (including MI), rehospitalization, and mortality are disproportionately higher in Black patients. Therefore, understanding differences in inflammation and resolution can enable the development of predictive, personalized, and precise treatment and attenuate sex/racial disparities. Thus, herein, we assess differences in bioactive lipids and SPMs, between Black and White patients experiencing an acute MI.
From the PRiME-GGAT cohort, we collected plasma after MI within 24-48 h from 22 Black (15 male and 7 female) and 31 White (23 male and 8 female) subjects for a comparative race-based and sex-based analyses. MI was confirmed using a biochemical measurement of plasma troponin and ST elevation. Plasma levels of three essential polyunsaturated fatty acids [arachidonic acid (AA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA)] and a set of 40 bioactive lipid mediators with major emphasis on SPMs were quantified by liquid chromatography-mass spectrometry. AA and DHA were higher in White male and female patients, and EPA was noted higher only in White male patients compared with White female and Black male and female patients. Lipoxygenase-mediated AA-derived 12-hydroxyeicosatetraenoic acid (29-63%) and 15-hydroxyeicosatetraenoic acid (3-9%) and DHA-derived 17-hydroxydocosahexaenoic acid (3-22%) and 14-hydroxydocosahexaenoic acid (7-10%) were major bioactive lipid mediators in plasma. The SPM signature resolvin E1 was significantly lower in Black patients compared with White male and female patients, whereas protectin D1 was lower in White male patients compared with White female and Black male and female patients.
Our comparative analyses of fatty acids and respective cyclooxygenase-derived and lipoxygenase-derived SPM signatures capture the heterogeneity of disease pathology and elucidate potential mechanisms underlying sex-based and race-based differences following MI.
白细胞导向的特异性促解决介质（SPM）对心脏修复至关重要，其生物合成与促炎介质的表达同时发生；然而，在急性心肌梗死（MI）事件期间按种族和性别特异性方式进行的精确定量了解甚少。冠心病是美国死亡和残疾的主要原因。尽管黑人和白人患者中冠心病的患病率相似，但黑人患者的心血管事件（包括MI）、再次住院和死亡率却高得多。因此，了解炎症和解决过程中的差异有助于开发预测性、个性化和精确的治疗方法，并减少性别/种族差异。因此，在本文中，我们评估了急性MI的黑人和白人患者之间生物活性脂质和SPM的差异。
从PRiME-GGAT队列中，我们在MI后24-48小时内收集了22名黑人（15名男性和7名女性）和31名白人（23名男性和8名女性）受试者的血浆，用于基于种族和性别的比较分析。使用血浆肌钙蛋白的生化测量和ST段抬高来确认MI。通过液相色谱-质谱法定量三种必需多不饱和脂肪酸[花生四烯酸（AA）、二十二碳六烯酸（DHA）和二十碳五烯酸（EPA）]的血浆水平以及一组40种主要侧重于SPM的生物活性脂质介质。与白人女性、黑人男性和女性患者相比，白人男性和女性患者的AA和DHA水平较高，仅白人男性患者的EPA水平高于白人女性、黑人男性和女性患者。脂氧合酶介导的AA衍生的12-羟基二十碳四烯酸（29-63%）和15-羟基二十碳四烯酸（3-9%）以及DHA衍生的17-羟基二十二碳六烯酸（3-22%）和14-羟基二十二碳六烯酸（7-10%）是血浆中的主要生物活性脂质介质。与白人男性和女性患者相比，黑人患者中SPM标志性介质消退素E1显著降低，而与白人女性、黑人男性和女性患者相比，白人男性患者中保护素D1降低。
我们对脂肪酸以及各自环氧化酶衍生和脂氧合酶衍生的SPM特征的比较分析捕捉了疾病病理的异质性，并阐明了MI后基于性别和种族差异的潜在机制。
