Procyanidins inhibit fine particulate matter-induced vascular smooth muscle cells apoptosis via the activation of the Nrf2 signaling pathway

Ecotoxicol Environ Saf. 2021 Oct 15:223:112586. doi: 10.1016/j.ecoenv.2021.112586. Epub 2021 Aug 4.

Abstract

The functional role of procyanidins (PC) in PM2.5-induced cardiovascular diseases (CVD) is largely unexplored. This study aimed to explore the protective effect of PC against PM2.5-induced vascular smooth muscle cells (VSMCs) apoptosis and underlying mechanisms. Sprague Dawley rats were pretreated with three doses of PC (50, 100, and 200 mg/kg) and exposed to 10 mg/kg PM2.5 by intratracheal instillation three times a week. VSMCs were exposed to 5, 10, and 20 μM PC before the addition of 100 μg/mL PM2.5. In vivo, the PM2.5 exposure induced apoptosis in the thoracic aorta of rats. The PM2.5 exposure significantly elevated the reactive oxygen species (ROS) and malondialdehyde (MDA) levels and decreased the superoxide dismutase activity. Also, PC supplementation increased the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), and its downstream antioxidant genes, i.e., NAD(P)H dehydrogenase (quinine) 1 and heme oxygenase 1, attenuated oxidative stress and vascular apoptosis. In vitro, PM2.5 induced cytotoxicity in VSMCs in a dose-dependent manner. Besides, PC abolished the PM2.5-induced cytotoxicity by activating the Nrf2 signal pathway, alleviating oxidative stress, and decreasing apoptosis. In conclusion, this work is the first study to demonstrate that PC can suppress the PM2.5-induced VSMCs apoptosis via the activation of the Nrf2 signal pathway.

Keywords: Apoptosis; Fine particulate matter; Nrf2; Oxidative stress; Procyanidins; Vascular smooth muscle cells.

MeSH terms

  • Animals
  • Apoptosis
  • Muscle, Smooth, Vascular / metabolism
  • NF-E2-Related Factor 2* / genetics
  • NF-E2-Related Factor 2* / metabolism
  • Oxidative Stress
  • Particulate Matter / metabolism
  • Particulate Matter / toxicity
  • Proanthocyanidins* / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species / metabolism
  • Signal Transduction

Substances

  • NF-E2-Related Factor 2
  • Particulate Matter
  • Proanthocyanidins
  • Reactive Oxygen Species