Enhanced p22phox expression impairs vascular function through p38 and ERK1/2 MAP kinase-dependent mechanisms in type 2 diabetic mice

Modar Kassan, Soo Kyoung Choi, Maria Galán, Young Ho Lee, Mohamed Trebak, Khalid Matrougui

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Type 2 diabetes is associated with vascular complication. We hypothesized that increased nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit p22phox expression impairs vascular endothelium-dependent relaxation (EDR) in type 2 diabetes. Type 2 diabetic (db-/db-) and control (db-/db+) mice were treated with reactive oxygen species (ROS) scavenger, polyethylene glycol superoxide dismutase (1,000 U/kg daily ip), or small interfering RNA p22phox (p22phox-lentivirus-small interfering RNA, 100 μg iv, 2 times/wk) for 1 mo. EDR was impaired in microvascular bed (coronary arteriole and femoral and mesenteric resistance arteries) from diabetic mice compared with control. Interestingly, ROS scavenger and p22phox downregulation did not affect blood glucose level or body weight but significantly improved EDR. Mitogen-activated protein kinases (ERK1/2 and p38) phosphorylation and NADPH oxidase activity were increased in arteries from diabetic mice and were reduced after ROS scavenger or p22phox downregulation in db-/db- mice. The present study showed that enhanced p22phox expression causes vascular dysfunction through ERK1/2 and p38-mitogen-activated protein kinase-dependent mechanisms in male type 2 diabetic mice. Therefore, p22phox could be an important target to improve vascular function in diabetes.

Original languageEnglish (US)
Pages (from-to)H972-H980
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume306
Issue number7
DOIs
StatePublished - Apr 1 2014

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Fingerprint Dive into the research topics of 'Enhanced p22<sup>phox</sup> expression impairs vascular function through p38 and ERK1/2 MAP kinase-dependent mechanisms in type 2 diabetic mice'. Together they form a unique fingerprint.

Cite this