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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
Summary
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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