Methylglyoxal enhances the proliferation of vascular smooth muscle cells via Akt phosphorylation


KIRÇA M.

JOURNAL OF RECEPTORS AND SIGNAL TRANSDUCTION, 2022 (Peer-Reviewed Journal) identifier identifier identifier

  • Publication Type: Article / Article
  • Publication Date: 2022
  • Doi Number: 10.1080/10799893.2022.2098328
  • Journal Name: JOURNAL OF RECEPTORS AND SIGNAL TRANSDUCTION
  • Journal Indexes: Science Citation Index Expanded, Scopus, Academic Search Premier, BIOSIS, Chemical Abstracts Core, EMBASE, MEDLINE
  • Keywords: Methylglyoxal, proliferation, vascular smooth muscle cell, Akt, ERK1, 2, high glucose, REACTIVE GLUCOSE METABOLITE

Abstract

Methylglyoxal (MGO) is predominantly produced as a by-product of the glycolysis pathway. The glyoxalase system effectively removes it in a healthy organism. However, this process is impaired, and MGO level is elevated in people with diabetes. MGO's effects on proliferation were mostly studied in cancer cells, and the data in other cell types are limited. This study inspected the proliferative capacity of MGO in vascular smooth muscle cells (VSMCs), which have a crucial role in atherosclerosis and restenosis. The roles of ERK1/2 MAPK and Akt phosphorylations in proliferation were determined. Telmisartan, irbesartan, and NF-kappa B inhibitor JSH-23's roles in protecting the cells from MGO-induced proliferation were also investigated. Primary VSMCs were isolated from the rat aorta. The proliferation was spectrophotometrically measured by using a tetrazolium salt (Wst-1). The cells were cultured in standard media (SM, glucose conc. 5.5 mM) or high glucose media (HGM, glucose conc. 25 mM; an in vitro model of hyperglycemia). ERK1/2 MAPK and Akt phosphorylations were determined by the western blot method. MGO triggered the proliferation at 24, 48, and 72 hrs in SM and 48 and 72 hrs in HGM. Low doses of MGO such as 1-10 mu M can induce proliferation. The phosphorylated ERK1/2 MAPK and Akt participated in MGO-induced proliferation. Telmisartan, irbesartan, and JSH-23 effectively alleviated the proliferation and Akt phosphorylation. MGO could proliferate VSMCs even at low doses. Moreover, hypertensive diabetic patients might benefit from a sartan family drug to protect VSMCs from MGO-induced proliferation.