Related Experiment Video
Updated: Nov 12, 2025
Understanding the Changes in Mitochondrial Morphology through Dynamic and Three-dimensional Fluorescence Micrographs
Published on: August 15, 2025
Chronic metformin treatment decreases cardiac injury during ischemia-reperfusion by attenuating endoplasmic reticulum
Qun Chen1, Jeremy Thompson1, Ying Hu1
1Departments of Medicine, Division of Cardiology, Virginia Commonwealth University, Richmond, VA 23298, USA.
Abstract:
Aging impairs mitochondrial function that leads to greater cardiac injury during ischemia and reperfusion. Cardiac endoplasm reticulum (ER) stress increases with age and contributes to mitochondrial dysfunction. Metformin is an anti-diabetic drug that protects cardiac mitochondria during acute ER stress. We hypothesized that metformin treatment would improve preexisting mitochondrial dysfunction in aged hearts by attenuating ER stress, followed by a decrease in cardiac injury during subsequent ischemia and reperfusion. Male young (3 mo.) and aged mice (24 mo.) received metformin (300 mg/kg/day) dissolved in drinking water with sucrose (0.2 g/100 ml) as sweetener for two weeks versus sucrose vehicle alone. Cytosol, subsarcolemmal (SSM), and interfibrillar mitochondria (IFM) were isolated. In separate groups, cardioprotection was evaluated using ex vivo isolated heart perfusion with 25 min. global ischemia and 60 min. reperfusion. Infarct size was measured. The contents of CHOP and cleaved ATF6 were decreased in metformin-treated 24 mo. mice compared to vehicle, supporting a decrease in ER stress. Metformin treatment improved OXPHOS in IFM in 24 mo. using a complex I substrate. Metformin treatment decreased infarct size following ischemia-reperfusion. Thus, metformin feeding decreased cardiac injury in aged mice during ischemia-reperfusion by improving pre-ischemic mitochondrial function via inhibition of ER stress.
Insights
Metformin treatment improved mitochondrial function and reduced cardiac injury in aged mice by decreasing endoplasmic reticulum (ER) stress. This study highlights metformin
Area of Science:
- Cardiovascular Biology
- Mitochondrial Medicine
- Aging Research
Background:
- Aging is associated with impaired mitochondrial function and increased cardiac susceptibility to ischemia-reperfusion (I/R) injury.
- Cardiac endoplasmic reticulum (ER) stress exacerbates mitochondrial dysfunction with age.
- Metformin, an anti-diabetic drug, shows potential for protecting cardiac mitochondria against acute ER stress.
Purpose of the Study:
- To investigate if metformin treatment can ameliorate pre-existing mitochondrial dysfunction in aged hearts.
- To determine if metformin attenuates ER stress and reduces cardiac injury during I/R in aged mice.
Main Methods:
- Aged (24 mo.) and young (3 mo.) mice received metformin or vehicle for two weeks.
- Mitochondrial function (OXPHOS) was assessed in isolated cardiac mitochondria.
- Cardiac ER stress markers (CHOP, cleaved ATF6) were quantified.
- Cardioprotection was evaluated using ex vivo heart perfusion with I/R, followed by infarct size measurement.
Main Results:
- Metformin treatment reduced ER stress markers (CHOP, cleaved ATF6) in aged mice.
- Metformin improved mitochondrial oxidative phosphorylation (OXPHOS) in interfibrillar mitochondria (IFM) of aged mice.
- Metformin administration significantly decreased infarct size following I/R in aged mice.
Conclusions:
- Metformin feeding mitigates cardiac injury in aged mice subjected to I/R.
- The cardioprotective effects of metformin are mediated by improved pre-ischemic mitochondrial function through ER stress inhibition.
- Metformin represents a potential therapeutic strategy for age-related cardiac dysfunction and I/R vulnerability.
More Related Videos
Related Concept Videos
01:46Electron Transport Chain: Complex I and II
ROS generation is regulated and maintained at moderate levels necessary...
01:26Oral Hypoglycemic Agents: Biguanides and Glitazones
01:26Effect of Hepatic Disease on Pharmacokinetics: Drug Dosing and Hepatic Blood Flow