Dynamic profiles of 25 serum biomarkers in acute myocardial infarction

Acute myocardial infarction (AMI) is a leading cause of cardiovascular mortality and perioperative complications in the elderly (>65 years). However, existing clinical biomarkers (e.g., troponin) still lack sufficient sensitivity for ultra-early diagnosis. A comprehensive understanding of the dynamic changes in serum biomarkers post-AMI is crucial for developing novel diagnostic strategies.

A rat AMI model was established by surgical ligation of the left anterior descending (LAD) coronary artery. Cardiac function was evaluated via echocardiography and triphenyltetrazolium chloride (TTC) staining at 24 h post-AMI. Blood samples were collected at baseline (pre-anesthesia) and at 1, 2, 6, 12, 24, and 48 h post-LAD ligation. Serum levels of 25 biomarkers were measured by ELISA, including: α-smooth muscle actin (α-SMA), aminopeptidase N (ANPEP), B-type natriuretic peptide (BNP), C-C chemokine receptor type 2 (CCR2), C-reactive protein (CRP), connective tissue growth factor (CTGF), C-X-C motif chemokine ligand 16 (CXCL16), cystatin C (Cys), dopamine D2 receptor (D2D), glucagon-like peptide-1 (GLP-1), homocysteine (Hcy), chemokine-like factor 1 (CKLF1), high-sensitivity troponin I (hs-TnI), interleukin-1β (IL-1β), interleukin-6 (IL-6), lipoprotein(a) (Lp-α), monocyte chemoattractant protein-1 (MCP-1), matrix metalloproteinase-9 (MMP-9), NOD-like receptor family pyrin domain-containing 3 (NLRP3), plasminogen activator inhibitor-1 (PAI-1), S100 calcium-binding protein A8 (S100A8), solute carrier family 31 member 1 (copper transporter, SLC31A1), tissue inhibitor of metalloproteinases-1 (TIMP-1), tumor necrosis factor-α (TNF-α), and vascular endothelial growth factor A (VEGF-A).

At 24 h post-AMI, LVEF was significantly decreased in the AMI group (63.84 ± 2.48% vs. 38.83 ± 2.62%, p < 0.001), with an infarct size of 28.70 ± 1.43%. A total of 25 blood biomarkers potentially associated with AMI were detected. Among them, 17 biomarkers showed rapid elevation within 1 h post-AMI (excluding IL-6, TNF-α, ANPEP, D2D, CXCL16, Lp-α and α-SMA). IL-6, TNF-α and ANPEP exhibited significant elevation at 2 h post-AMI, while CXCL16 showed obvious elevation at 6 h and α-SMA demonstrated significant elevation at 12 h. However, S100A8, GLP-1, MMP-9 and NLRP3 showed a decrease at 2 h, although their overall trend within 48 h was upward. Lp-α and D2D remained below baseline levels throughout the observation period, with both showing levels below baseline at 1 h post-AMI. They returned to baseline levels at 12 h and 2 h respectively, followed by rapid decreases again.

This study is the first to systematically characterize the dynamic profiles of 25 serum biomarkers following AMI in rats, revealing that: (1) IL-1β, S100A8, BNP, SLC31A1 and Cys may serve as an ultra-early (1 h) diagnostic panel (increase of over 70% at 1 h); (2) the delayed elevation of α-SMA and CXCL16 may be associated with the initiation of myocardial repair; (3) the suppression of Lp-α and D2D might reflect compensatory protective mechanisms.