Endoplasmic reticulum stress in the heart

Research output: Contribution to journalReview articlepeer-review

169 Scopus citations

Abstract

Over the last decade, it has become clear that the accumulation of misfolded proteins contributes to a number of neurodegenerative, immune, and endocrine pathologies, as well as other age-related illnesses. Recent interest has focused on the possibility that the accumulation of misfolded proteins can also contribute to vascular and cardiac diseases. In large part, the misfolding of proteins takes place during synthesis on free ribosomes in the cytoplasm or on endoplasmic reticulum ribosomes. In fact, even under optimal conditions, ≈30% of all newly synthesized proteins are rapidly degraded, most likely because of improper folding. Accordingly, stresses that perturb the folding of proteins during or soon after synthesis can lead to the accumulation of misfolded proteins and to potential cellular dysfunction and pathological consequences. To avert such outcomes, cells have developed elaborate protein quality-control systems for detecting misfolded proteins and making appropriate adjustments to the machinery responsible for protein synthesis and/or degradation. Important contributors to protein quality control include cytosolic and organelle-targeted molecular chaperones, which help fold and stabilize proteins from unfolding, and the ubiquitin proteasome system, which degrades terminally misfolded proteins. Both of these systems play important roles in cardiovascular biology. The focus of this review is the endoplasmic reticulum stress response, a protein quality-control and signal-transduction system that has not been well studied in the context of cardiovascular biology but that could be important for vascular and cardiac health and disease.

Original languageEnglish (US)
Pages (from-to)975-984
Number of pages10
JournalCirculation research
Volume101
Issue number10
DOIs
StatePublished - Nov 2007
Externally publishedYes

Keywords

  • ATF6
  • ER stress
  • Ischemia
  • Unfolded protein response
  • XBP1

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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