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Objective <p>This study aimed to examine the cardioprotective effects of bivalirudin in an in vitro model of hypoxia/reoxygenation (H/R) injury using AC16 human cardiomyocytes, with a focus on elucidating the underlying molecular pathways and key regulatory mechanisms involved.</p> Methods <p>An H/R injury model was established in AC16 human cardiomyocytes. Cells were assigned to one of three groups: untreated control, H/R model, and H/R + bivalirudin intervention. Cellular proliferation and apoptosis were evaluated using the Cell Counting Kit-8 (CCK-8) assay and flow cytometry, respectively. Levels of lactate dehydrogenase (LDH), reactive oxygen species (ROS), superoxide dismutase (SOD), and malondialdehyde (MDA) were measured using biochemical assay kits. Concentrations of creatine kinase-MB (CK-MB), cardiac troponin T (cTnT), and brain natriuretic peptide (BNP) were quantified via enzyme-linked immunosorbent assay. Protein expression of ERK1/2, phosphorylated ERK1/2 (p-ERK1/2), AKT, phosphorylated AKT (p-AKT), BCL-2, BAX, and caspase-3 was assessed through Western blot analysis.</p> Results <p>Cell viability was significantly improved in the H/R + bivalirudin group relative to the H/R model group (<i>p</i> &lt; 0.05). Bivalirudin notably attenuated H/R-induced elevations in intracellular ROS, MDA, and LDH levels, while restoring SOD activity (<i>p</i> &lt; 0.05). Furthermore, levels of CK-MB, cTnT, and BNP were significantly reduced following bivalirudin treatment (<i>p</i> &lt; 0.05). Western blot results showed increased expression of p-ERK1/2, p-AKT, and the anti-apoptotic marker BCL-2, along with decreased levels of the pro-apoptotic proteins caspase-3 and BAX (<i>p</i> &lt; 0.05).</p> Conclusions <p>Bivalirudin conferred protection against H/R-induced apoptosis in AC16 human cardiomyocytes, in part by modulating oxidative stress responses and activating the ERK1/2-MAPK and PI3K–Akt signaling pathways. These findings enhance understanding of the molecular basis of bivalirudin-mediated cardioprotection in the context of myocardial ischemia–reperfusion injury.</p>

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Molecular mechanisms of bivalirudin-induced cardioprotection in myocardial ischemia–reperfusion injury

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月7日

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  • Xiu-Fen Li,
  • Gu-Zhuo Shen,
  • Wen-Ding Chen,
  • Remilai Tailaiti,
  • Shi-Shi Tang,
  • Yan Yang,
  • Peng-Fei Gong,
  • Paerhati Tuerxun

摘要

Objective

This study aimed to examine the cardioprotective effects of bivalirudin in an in vitro model of hypoxia/reoxygenation (H/R) injury using AC16 human cardiomyocytes, with a focus on elucidating the underlying molecular pathways and key regulatory mechanisms involved.

Methods

An H/R injury model was established in AC16 human cardiomyocytes. Cells were assigned to one of three groups: untreated control, H/R model, and H/R + bivalirudin intervention. Cellular proliferation and apoptosis were evaluated using the Cell Counting Kit-8 (CCK-8) assay and flow cytometry, respectively. Levels of lactate dehydrogenase (LDH), reactive oxygen species (ROS), superoxide dismutase (SOD), and malondialdehyde (MDA) were measured using biochemical assay kits. Concentrations of creatine kinase-MB (CK-MB), cardiac troponin T (cTnT), and brain natriuretic peptide (BNP) were quantified via enzyme-linked immunosorbent assay. Protein expression of ERK1/2, phosphorylated ERK1/2 (p-ERK1/2), AKT, phosphorylated AKT (p-AKT), BCL-2, BAX, and caspase-3 was assessed through Western blot analysis.

Results

Cell viability was significantly improved in the H/R + bivalirudin group relative to the H/R model group (p < 0.05). Bivalirudin notably attenuated H/R-induced elevations in intracellular ROS, MDA, and LDH levels, while restoring SOD activity (p < 0.05). Furthermore, levels of CK-MB, cTnT, and BNP were significantly reduced following bivalirudin treatment (p < 0.05). Western blot results showed increased expression of p-ERK1/2, p-AKT, and the anti-apoptotic marker BCL-2, along with decreased levels of the pro-apoptotic proteins caspase-3 and BAX (p < 0.05).

Conclusions

Bivalirudin conferred protection against H/R-induced apoptosis in AC16 human cardiomyocytes, in part by modulating oxidative stress responses and activating the ERK1/2-MAPK and PI3K–Akt signaling pathways. These findings enhance understanding of the molecular basis of bivalirudin-mediated cardioprotection in the context of myocardial ischemia–reperfusion injury.