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CUL5-Mediated Visfatin (NAMPT) Degradation Blocks Endothelial Proliferation and Angiogenesis via the MAPK/PI3K-AKT

Zanhua Shi1,2, Jiamei Yao3, Xinhua Ma2

  • 1Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.

Journal of Cardiovascular Pharmacology
|October 1, 2021
PubMed

Insights

Nicotinamide phosphoribosyltransferase (NAMPT) protects against oxidative stress in human coronary artery endothelial cells (HCAECs). NAMPT enhances cell viability and angiogenesis, counteracting CUL5-induced dysfunction.

Area of Science:

  • Cardiovascular Biology
  • Cellular Mechanisms
  • Molecular Interactions

Background:

  • Endothelial dysfunction and aberrant angiogenesis are key in cardiovascular diseases.
  • The vascular endothelial growth factor (VEGF)-matrix metalloproteinases (MMP) system is crucial for angiogenesis.
  • Nicotinamide phosphoribosyltransferase (NAMPT) is recognized for its role in promoting endothelial function and angiogenesis.

Purpose of the Study:

  • To investigate the protective role of NAMPT against oxidative stress in human coronary artery endothelial cells (HCAECs).
  • To identify interacting proteins with NAMPT and elucidate their functional relationship in endothelial cells.
  • To explore the signaling pathways involved in NAMPT-mediated protection.

Main Methods:

  • Overexpression of NAMPT and CUL5 in HCAECs.
  • Assessment of cell viability, apoptosis, motility, and tube formation.
  • Protein-protein interaction analysis using databases (Mentha, BioGrid) and validation via Co-immunoprecipitation (Co-IP).
  • Western blot analysis to measure phosphorylation of p38 and Akt, and protein levels of VEGF and MMP2.

Main Results:

  • NAMPT overexpression protected HCAECs from H2O2-induced injury, enhancing viability, motility, and tube formation while inhibiting apoptosis.
  • CUL5 was identified as a NAMPT-interacting protein that suppresses NAMPT expression and exacerbates H2O2-induced HCAEC dysfunction.
  • NAMPT overexpression counteracted CUL5's detrimental effects, modulating p38/Akt/VEGF/MMP signaling pathways.

Conclusions:

  • CUL5 interacts with NAMPT in H2O2-stimulated HCAECs, negatively impacting cell viability and promoting apoptosis.
  • NAMPT overexpression confers protection against oxidative stress by improving endothelial cell function and angiogenesis.
  • The findings highlight a novel interaction between NAMPT and CUL5, with implications for understanding cardiovascular disease pathogenesis.

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