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ER Protein Quality Control and the Unfolded Protein Response in the Heart

A Arrieta1, E A Blackwood1, C C Glembotski2

  • 1San Diego State University Heart Institute and the Department of Biology, San Diego State University, San Diego, CA, 92182, USA.

Current Topics in Microbiology and Immunology
|October 14, 2017
PubMed

Insights

Cardiac myocyte growth challenges endoplasmic reticulum-protein quality control (ER-PQC) and the unfolded protein response (UPR). While sufficient in physiological states, ER-PQC and UPR are insufficient in pathological conditions like heart failure.

Area of Science:

  • Cardiovascular Biology
  • Cellular Stress Response

Background:

  • Cardiac myocytes are essential for heart function and undergo growth under various conditions.
  • Endoplasmic reticulum-protein quality control (ER-PQC) and the unfolded protein response (UPR) are critical cellular processes.
  • ER-PQC and UPR maintain cardiac myocyte function during physiological growth.

Purpose of the Study:

  • To investigate the role of ER-PQC and UPR in cardiac myocyte growth.
  • To compare ER-PQC and UPR function in physiological versus pathological cardiac growth.
  • To discuss the adaptive or maladaptive nature of the UPR in cardiac conditions.

Main Methods:

  • The study reviews existing literature on ER-PQC and UPR in cardiac myocytes.
  • It analyzes the impact of physiological conditions (development, exercise, pregnancy) on ER-PQC and UPR.
  • It examines the effects of pathological conditions (myocardial infarction, heart failure) on ER-PQC and UPR.

Main Results:

  • ER-PQC and UPR are sufficient to support cardiac myocyte hypertrophy during physiological growth.
  • ER-PQC and UPR are insufficient to manage cardiac myocyte growth challenges in pathological states.
  • Expression of adaptive UPR components declines with age and during myocardial pathology.

Conclusions:

  • The UPR's effectiveness in cardiac myocytes is context-dependent, being adaptive in physiological growth but insufficient in pathological hypertrophy.
  • Declining UPR component expression contributes to the failure of ER-PQC under pathological stress.
  • Further research is needed to understand the adaptive versus maladaptive roles of the UPR in heart disease.

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