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Requirement of JNK1 for endothelial cell injury in atherogenesis

Narges Amini1, Joseph J Boyle1, Britta Moers2

  • 1British Heart Foundation Cardiovascular Sciences Unit, National Heart and Lung Institute, Imperial College London, UK.

Atherosclerosis
|June 24, 2014
PubMed
Abstract

Insights

c-Jun N-terminal kinase 1 (JNK1) promotes endothelial cell apoptosis and lesion formation in atherosclerosis. Inhibiting JNK1 may reduce cardiovascular disease by preventing endothelial cell injury and foam cell development.

Area of Science:

  • Molecular biology
  • Cardiovascular research
  • Cellular signaling

Background:

  • The c-Jun N-terminal kinase (JNK) pathway regulates critical cellular functions, including apoptosis and metabolism.
  • While JNK2's role in atherosclerosis is established, JNK1's specific contribution to endothelial cell (EC) injury and early lesion development remains unclear.

Purpose of the Study:

  • To investigate the role of JNK1 and its regulator MAP kinase phosphatase-1 (MKP-1) in EC injury and early atherosclerosis.
  • To determine if JNK1 influences EC apoptosis and lipid deposition in a mouse model of hypercholesterolemia.

Main Methods:

  • Utilized hypercholesterolemic LDLR(-/-) mice and LDLR(-/-)/JNK1(-/-) mice fed a high-fat diet for six weeks.
  • Assessed endothelial cell apoptosis using cleaved caspase-3 staining and lipid deposition via Sudan IV staining.

Main Results:

  • Genetic deletion of JNK1 significantly reduced EC apoptosis and atherosclerotic lesion formation in hypercholesterolemic mice.
  • Conversely, deletion of MKP-1 enhanced EC apoptosis but did not alter lesion formation compared to control mice.

Conclusions:

  • JNK1 is essential for EC apoptosis and lipid deposition in the early stages of atherosclerosis.
  • Targeting JNK1 pharmacologically could offer a dual therapeutic strategy for atherosclerosis, addressing both EC injury and foam cell formation.
Keywords:
ApoptosisAtherosclerosisEndothelial cellsMAP kinase phosphatasec-Jun N-terminal kinase

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