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Updated: Dec 20, 2025
Acute Myocardial Infarction in Rats
Published on: February 16, 2011
Mitochondrial Dysfunction Secondary to Endoplasmic Reticulum Stress in Acute Myocardial Ischemic Injury in Rats
Chaoyi Qin1, Xue-Lin Wu2, Jun Gu1
1Department of Cardiovascular Surgery, West China Hospital, Chengdu, Sichuan, China (mainland).
Abstract:
BACKGROUND The relationship between endoplasmic reticulum and mitochondria during acute myocardial ischemic injury is still unclear. Our study aimed to define the dynamics of endoplasmic reticulum stress and mitochondrial dysfunction during acute ischemic injury. MATERIAL AND METHODS A rat model of acute myocardial infarction and hypoxic cardiomyocytes were used in this study. Groups were set at 0 hours, 1 hour, 2 hours, 4 hours, and 6 hours after ischemic injury for both in vivo and in vitro studies. ATF6 and GRP-78 were examined to indicate endoplasmic reticulum stress. Cellular ATP and cytosolic levels of mitochondrial DNA and cytochrome c were detected to evaluate mitochondrial dysfunction. Caspase-3 was used for apoptosis analysis. RESULTS Our results showed that both mRNA and protein levels of ATF6 and GRP-78 were elevated from 1 hour after ischemic injury in vivo and in vitro (P<0.05). However, ATP levels were increased at 2 hours after ischemic injury and significantly decreased from 4 hours after ischemic injury in vivo, while ATP level of cultured cardiomyocytes decreased remarkably from 2 hours after ischemic injury (P<0.05). Cytosolic mitochondrial DNA levels began to increase from 2 hours after ischemic injury (P<0.05). Cytosolic levels of cytochrome c increased from 4 hours after ischemic injury. Additionally, both mRNA and protein expressions of caspase-3 started to significantly elevate at 6 hours after ischemic injury (P<0.05). CONCLUSIONS The present study suggested that mitochondrial dysfunction was secondary to endoplasmic reticulum stress, which provides a novel experimental foundation for further exploration of the detailed mechanism after ischemic injury, especially the interaction between endoplasmic reticulum and mitochondria.
Insights
Endoplasmic reticulum stress precedes mitochondrial dysfunction during acute myocardial infarction. This study reveals that ER stress markers increase early, followed by impaired mitochondrial function and apoptosis in heart injury.
Area of Science:
- Cardiovascular Biology
- Cellular Stress Response
- Mitochondrial Dynamics
Background:
- The interplay between endoplasmic reticulum (ER) stress and mitochondrial dysfunction in acute myocardial ischemic injury remains poorly understood.
- Investigating these cellular events is crucial for understanding heart attack pathology.
Purpose of the Study:
- To elucidate the temporal relationship between endoplasmic reticulum stress and mitochondrial dysfunction following acute ischemic injury.
- To define the dynamic changes in cellular markers of ER stress and mitochondrial integrity.
Main Methods:
- Utilized a rat model of acute myocardial infarction and in vitro hypoxic cardiomyocytes.
- Assessed endoplasmic reticulum stress via ATF6 and GRP-78 expression.
- Evaluated mitochondrial dysfunction through ATP levels, cytosolic mitochondrial DNA, and cytochrome c release.
- Quantified apoptosis using Caspase-3 activity.
Main Results:
- Elevated endoplasmic reticulum stress markers (ATF6, GRP-78) observed from 1 hour post-injury.
- Mitochondrial dysfunction indicated by decreased ATP levels (from 2-4 hours) and increased cytosolic mitochondrial DNA (from 2 hours).
- Cytochrome c release and Caspase-3 activation occurred later (from 4-6 hours), suggesting secondary apoptosis.
Conclusions:
- Mitochondrial dysfunction appears to be a consequence of endoplasmic reticulum stress during acute myocardial ischemia.
- Findings suggest a sequential mechanism where ER stress initiates a cascade leading to mitochondrial damage and cell death.
- Provides a foundation for exploring therapeutic strategies targeting the ER-mitochondria axis in heart attack treatment.
