Early Growth Response-1 Promotes Atherogenesis: Mice Deficient in Early Growth Response-1 and Apolipoprotein E Display Decreased Atherosclerosis and Vascular Inflammation

Evis Harja, Loredana G. Bucciarelli, Yan Lu, David M. Stern, Yu Shan Zou, Ann Marie Schmidt, Shi Fang Yan

Research output: Contribution to journalArticle

Abstract

Early growth response-1 (Egr-1) regulates expression of proinflammatory and procoagulant genes in acute cell stress. Experimental evidence suggested that Egr-1 transcripts were upregulated in human atherosclerotic plaques versus adjacent unaffected tissue. To test the impact of Egr-1 in chronic vascular stress, we examined its role in a murine model of atherosclerosis. Real-time PCR analysis of aortae retrieved from apoE -/- mice demonstrated increased Egr-1 transcripts in an age-dependent manner, compared with aortae retrieved from C57BL/6 control animals. Therefore, homozygous Egr-1 -/- mice were bred into the apoE -/- background. Homozygous double-knockout mice (Egr-1 -/-/ apoE -/-) in the C57BL/6 background were maintained on normal chow diet. At age 14 and 24 weeks, atherosclerotic lesion area and complexity at the aortic root were strikingly decreased in mice deficient in both Egr-1 and apoE compared with mice deficient in apoE alone. In parallel, transcripts for genes regulating the inflammatory/prothrombotic response were diminished in Egr-1 -/-/apoE -/- aortae versus apoE -/-. In vitro, oxidized low-density lipoprotein (OxLDL), a key factor inciting atherogenic mechanisms in the vasculature, upregulated Egr-1 expression in monocytes via the MEK-ERK1/2 pathway. We conclude that Egr-1 broadly regulates expression of molecules critically linked to atherogenesis and lesion progression.

Original languageEnglish
Pages (from-to)333-339
Number of pages7
JournalCirculation Research
Volume94
Issue number3
DOIs
Publication statusPublished - Feb 20 2004

Keywords

  • Atherosclerosis
  • Hypercholesterolemia
  • Oxidized low-density lipoprotein
  • Signaling pathway
  • Transcription factor

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'Early Growth Response-1 Promotes Atherogenesis: Mice Deficient in Early Growth Response-1 and Apolipoprotein E Display Decreased Atherosclerosis and Vascular Inflammation'. Together they form a unique fingerprint.

  • Cite this