Impairment of Autophagy Mediates the Uric-Acid-Induced Phenotypic Transformation of Vascular Smooth Muscle Cells

Pharmacology. 2024;109(1):34-42. doi: 10.1159/000534929. Epub 2023 Nov 27.

Abstract

Introduction: Hyperuricemia may be involved in the phenotypic transformation of vascular smooth muscle cells, thus promoting the occurrence of atherosclerosis, and autophagy may be one of the important links, but little is known about the specific molecular mechanism.

Methods: We established a mouse model of hyperuricemia and studied the relationship between changes in autophagy levels and the phenotypic transformation of muscle cells.

Results: Our study found that high uric acid levels promote the phenotypic transformation of muscle cells by inhibiting autophagy, thus enhancing their proliferation and migration abilities. If autophagy is restored, phenotypic transformation can be reversed by reducing the levels of the transcription factor Kruppel-like factor 4.

Conclusion: Uric acid may induce the phenotypic transformation of muscle cells and promote the occurrence of atherosclerosis by disrupting normal autophagy.

Keywords: Atherosclerosis; Autophagy; Kruppel-like factor 4; Uric acid; Vascular smooth muscle cells.

MeSH terms

  • Animals
  • Atherosclerosis* / chemically induced
  • Autophagy
  • Cell Proliferation
  • Cells, Cultured
  • Hyperuricemia* / chemically induced
  • Mice
  • Muscle, Smooth, Vascular
  • Myocytes, Smooth Muscle
  • Uric Acid

Substances

  • Uric Acid