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<p>Atherosclerosis is the primary cause of most cases of coronary artery disease, peripheral arterial disease, and many strokes. It is characterized by pathological vascular smooth muscle cell hyperplasia. Current treatment regimens are associated with several adverse effects including hepatotoxicity, hemorrhagic complications, and non-selective cellular inhibition. Plaque stabilization and angiogenesis are critical for mitigating adverse cardiovascular outcomes. Stabilized plaques exhibit reduced vulnerability to rupture, thereby lowering the risk of thrombus formation, myocardial infarction, and ischemic stroke. Transforming Growth Factor Beta 1 (TGF-β1cells) is instrumental in promoting angiogenesis, facilitating the regrowth of endothelial cells, and contributing to the stabilization of atherosclerotic plaques. Anti-miRNA 21 can lead to plaque stabilization by decreasing inflammation and limiting the growth of smooth muscle cells while encouraging cell death, which helps prevent plaque rupture. This research investigates a novel combination therapy utilizing anti-miR-21 and baculovirus expressing TGF-β1 gene for vascular tissue regeneration. A hemocompatible nanocomposite hydrogel with remarkable cellular adhesion profile was prepared by encapsulating anti-miR-21 and baculovirus expressing TGF-β1 gene in PLGA nanoparticles, followed by embedding them in a gelatin-genipin crosslinked nanocomposite hydrogel. Chorioallantoic membrane assay in chicken embryo and PTEN quantification study was used for angiogenesis. MTT assay followed by Annexin V-FITC/PI stained flowcytometry was used for HASMCs apoptosis study. The combination therapy demonstrates synergistic effects through dual mechanisms: promoting neo-vascularization via selective endothelial cell proliferation while inducing arterial smooth muscle cell apoptosis (22.27 ± 1.2%) to control extracellular matrix secretion and stabilize plaque. The therapeutic efficacy is evidenced by significant reduction in PTEN expression (251.1 ±16&#xa0;pg/ml compared to 375.2 ± 5.29&#xa0;pg/ml in control) and enhanced angiogenic responses in the CAM assay, showing a 126.46 ± 16.62% increase in vessel length.</p>

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A high-performance hydrogel platform enabling dual anti-miR-21 and TGF-β1 delivery to improve arterial plaque stability and enhance therapeutic angiogenesis outcomes

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月23日

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  • Paromita Islam,
  • Ahmed Abosalha,
  • Sabrina Schaly,
  • Jacqueline L. Boyajian,
  • Amal Kassab,
  • Stephanie Makhlouf,
  • Madison Santos,
  • Editha Renesteen,
  • Cedrique Shum-Tim,
  • Arghya Pal,
  • Dominique Shum-Tim,
  • Satya Prakash

摘要

Atherosclerosis is the primary cause of most cases of coronary artery disease, peripheral arterial disease, and many strokes. It is characterized by pathological vascular smooth muscle cell hyperplasia. Current treatment regimens are associated with several adverse effects including hepatotoxicity, hemorrhagic complications, and non-selective cellular inhibition. Plaque stabilization and angiogenesis are critical for mitigating adverse cardiovascular outcomes. Stabilized plaques exhibit reduced vulnerability to rupture, thereby lowering the risk of thrombus formation, myocardial infarction, and ischemic stroke. Transforming Growth Factor Beta 1 (TGF-β1cells) is instrumental in promoting angiogenesis, facilitating the regrowth of endothelial cells, and contributing to the stabilization of atherosclerotic plaques. Anti-miRNA 21 can lead to plaque stabilization by decreasing inflammation and limiting the growth of smooth muscle cells while encouraging cell death, which helps prevent plaque rupture. This research investigates a novel combination therapy utilizing anti-miR-21 and baculovirus expressing TGF-β1 gene for vascular tissue regeneration. A hemocompatible nanocomposite hydrogel with remarkable cellular adhesion profile was prepared by encapsulating anti-miR-21 and baculovirus expressing TGF-β1 gene in PLGA nanoparticles, followed by embedding them in a gelatin-genipin crosslinked nanocomposite hydrogel. Chorioallantoic membrane assay in chicken embryo and PTEN quantification study was used for angiogenesis. MTT assay followed by Annexin V-FITC/PI stained flowcytometry was used for HASMCs apoptosis study. The combination therapy demonstrates synergistic effects through dual mechanisms: promoting neo-vascularization via selective endothelial cell proliferation while inducing arterial smooth muscle cell apoptosis (22.27 ± 1.2%) to control extracellular matrix secretion and stabilize plaque. The therapeutic efficacy is evidenced by significant reduction in PTEN expression (251.1 ±16 pg/ml compared to 375.2 ± 5.29 pg/ml in control) and enhanced angiogenic responses in the CAM assay, showing a 126.46 ± 16.62% increase in vessel length.