Department of Cardiology, Centro Hospitalar Vila Nova de Gaia/Espinho, Vila Nova de Gaia, Portugal.
Department of Surgery and Physiology, Cardiovascular R&D Centre - UnIC@RISE, Faculty of Medicine of the University of Porto, Porto, Portugal.
ESC Heart Fail. 2024 Feb;11(1):209-218. doi: 10.1002/ehf2.14465. Epub 2023 Nov 8.
We aim to characterize the clinical and proteomic profiles of patients at risk of developing heart failure (HF), with and without coronary artery disease (CAD) or prior myocardial infarction (MI).
HOMAGE evaluated the effect of spironolactone on plasma and serum markers of fibrosis over 9 months of follow-up in participants with (or at risk of having) CAD, and raised natriuretic peptides. In this post hoc analysis, patients were classified as (i) neither CAD nor MI; (ii) CAD; or (iii) MI. Proteomic between-group differences were evaluated through logistic regression and narrowed using backward stepwise selection and bootstrapping. Among the 527 participants, 28% had neither CAD or MI, 31% had CAD, and 41% had prior MI. Compared with people with neither CAD nor MI, those with CAD had higher baseline plasma concentrations of matrix metalloproteinase-7 (MMP-7), galectin-4 (GAL4), plasminogen activator inhibitor 1 (PAI-1), and lower plasma peptidoglycan recognition protein 1 (PGLYRP1), whilst those with a history of MI had higher plasma MMP-7, neurotrophin-3 (NT3), pulmonary surfactant-associated protein D (PSPD), and lower plasma tumour necrosis factor-related activation-induced cytokine (TRANCE). Proteomic signatures were similar for patients with CAD or prior MI. Treatment with spironolactone was associated with an increase of MMP7, NT3, and PGLYRP1 at 9 months.
In patients at risk of developing HF, those with CAD or MI had a different proteomic profile regarding inflammatory, immunological, and collagen catabolic processes.
本研究旨在描述发生心力衰竭（HF）风险的患者的临床和蛋白质组学特征，包括合并或不合并冠状动脉疾病（CAD）或既往心肌梗死（MI）的患者。
HOMAGE 研究评估了螺内酯对 CAD 患者（或有 CAD 风险的患者）和升高的利钠肽患者在 9 个月随访期间的血浆和血清纤维化标志物的影响。在本事后分析中，患者被分为（i）既无 CAD 也无 MI；（ii）CAD；或（iii）MI。通过逻辑回归评估组间蛋白质组学差异，并使用向后逐步选择和自举法进行缩小。在 527 名参与者中，28%既无 CAD 也无 MI，31%有 CAD，41%有既往 MI。与既无 CAD 也无 MI 的患者相比，CAD 患者的基线血浆基质金属蛋白酶-7（MMP-7）、半乳糖凝集素-4（GAL4）、纤溶酶原激活物抑制剂 1（PAI-1）浓度更高，而肽聚糖识别蛋白 1（PGLYRP1）浓度更低，而既往 MI 患者的血浆 MMP-7、神经生长因子-3（NT3）、肺表面活性剂相关蛋白 D（PSPD）浓度更高，肿瘤坏死因子相关激活诱导细胞因子（TRANCE）浓度更低。CAD 或既往 MI 患者的蛋白质组学特征相似。螺内酯治疗 9 个月后与 MMP7、NT3 和 PGLYRP1 的增加相关。
在发生 HF 风险的患者中，CAD 或 MI 患者的炎症、免疫和胶原代谢过程的蛋白质组学特征不同。
