Subthreshold High-Frequency Electrical Field Stimulation Induces VEGF Expression in Cardiomyocytes

Area of Science:

• Cardiovascular Research
• Regenerative Medicine
• Molecular Biology

Background:

• Subthreshold electrical stimulation (SES) enhances angiogenesis in skeletal muscles via vascular endothelial growth factor (VEGF).
• Cardiomyocytes can synthesize and secrete VEGF, a crucial factor in angiogenesis.
• Ischemic heart disease necessitates novel therapeutic angiogenesis approaches.

Purpose of the Study:

• To investigate the effect of SES on VEGF regulation in cultured neonatal rat ventricular myocytes (NRVMs).
• To explore SES as a potential method for therapeutic angiogenesis in ischemic heart disease.

Main Methods:

• NRVMs were subjected to SES (0.5 V/cm, 1 ms bipolar impulse) at various frequencies (5-99 Hz) for 48 hours.
• VEGF and KDR (VEGF receptor) expression were quantified using Western blot and ELISA.
• Biological activity of secreted VEGF was assessed by culturing human coronary artery endothelial cells (HCAECs) with NRVM supernatant.

Main Results:

• SES at 25 Hz significantly increased intracellular and secreted VEGF protein levels in NRVMs.
• A significant decrease in KDR receptor protein expression was observed concurrently with increased VEGF.
• Supernatant from SES-treated NRVMs enhanced HCAEC proliferation, indicating biologically active VEGF.

Conclusions:

• Cardiomyocytes respond to SES by upregulating biologically active VEGF.
• This SES-induced VEGF promotes endothelial cell proliferation, suggesting a novel mechanism for therapeutic angiogenesis.
• SES presents a promising avenue for developing new treatments for ischemic heart conditions.