Effects of Low-Dose Atorvastatin on the Peripheral Blood Mononuclear Cell Secretion of Angiogenic Factors in Type 2 Diabetes

Biomolecules. 2021 Dec 15;11(12):1885. doi: 10.3390/biom11121885.

Abstract

The aim of this study was to investigate the influence of statins on the secretion of angiogenesis mediators by the peripheral blood mononuclear cells (PBMCs) derived from patients suffering from type 2 diabetes. The study group comprised 30 participants and included: 10 statin-treated patients with diabetes, 10 statin-free diabetic subjects, and 10 statin-free non-diabetic individuals. PBMCs isolated from the blood were cultured in vitro in standard conditions and in an environment mimicking hyperglycemia. Culture supernatants were evaluated for VEGF, MCP-1, Il-10, and Il-12 by flow cytometry using commercial BDTM. Cytometric Bead Array tests. The secretion of VEGF, MCP-1 and Il-12 by PBMCs, cultured both in standard and hyperglycemic conditions, was significantly lower in the statin-treated patients with type 2 diabetes in comparison with the statin-free diabetic patients. Conversely, the secretion of Il-10 was higher in the statin-treated than in the statin-free diabetic patients. VEGF, MCP-1 and Il-12 levels in PBMCs supernatants from the glucose-containing medium were higher than those from the standard medium in each of the diabetic groups. The results of the study suggest that statins in low doses exhibit an antiangiogenic activity, reducing the secretion of potent proangiogenic factors, such as VEGF and MCP-1, and increasing the secretion of antiangiogenic Il-10 by PBMCs, also under hyperglycemic conditions characteristic for type 2 diabetes.

Keywords: angiogenic factors; diabetes; hyperglycemia; peripheral blood mononuclear cells; statins.

Publication types

  • Comparative Study

MeSH terms

  • Angiogenesis Inducing Agents / metabolism*
  • Angiogenesis Inhibitors / administration & dosage*
  • Angiogenesis Inhibitors / pharmacology
  • Atorvastatin / administration & dosage*
  • Atorvastatin / pharmacology
  • Case-Control Studies
  • Cells, Cultured
  • Chemokine CCL2 / metabolism
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation / drug effects
  • Humans
  • Interleukin-10 / metabolism
  • Interleukin-12 / metabolism
  • Leukocytes, Mononuclear / cytology*
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / metabolism
  • Models, Biological
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Angiogenesis Inducing Agents
  • Angiogenesis Inhibitors
  • CCL2 protein, human
  • Chemokine CCL2
  • IL10 protein, human
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Interleukin-10
  • Interleukin-12
  • Atorvastatin