J Korean Med Sci.  2022 Mar;37(9):e55. 10.3346/jkms.2022.37.e55.

Surgically Metabolic Resection of Pericardial Fat to Ameliorate Myocardial Mitochondrial Dysfunction in Acute Myocardial Infarction Obese Rats

• Kang KW
• Ko JY
• Lee H
• Shin SY
• Lee WS
• Hong J
• Kim SW
• Lee SK
• Oak MH

• KMID: 2526967
• DOI: http://doi.org/10.3346/jkms.2022.37.e55

Abstract

Background
Pericardial fat (PF) is highly associated with cardiovascular disease but the effectiveness of surgical resection of PF is still unknown for myocardial mitochondrial structure and function in acute myocardial infarction (AMI) with obesity. The aim of this study was to demonstrate the difference in myocardial mitochondrial structure and function between obese AMI with additionally resected PF and those without resected PF.
Methods
Obese rats with 12-week high fat diet (45 kcal% fat, n = 21) were randomly assigned into 3 groups: obese control, obese AMI and obese AMI with additionally resected PF. One week after developing AMI and additional resection of PF, echocardiogram, myocardial mitochondrial histomorphology, oxidative phosphorylation system (OXPHOS), anti-oxidative enzyme and sarcoplasmic reticulum Ca ²⁺ ATPase 2 (SERCA2) in the non-infarcted area were assessed between these groups.
Results
There was significant improvement of systolic function in AMI with PF resection compared with the AMI group in the echocardiogram. Even though the electron microscopic morphology for the mitochondria seems to be similar between the AMI with PF resection and AMI groups, there was an improved expression of PGC-1α and responsive OXPHOS including NDUFB3, NDUFB5 and SDHB are associated with the ATP levels in the AMI with PF resection compared with those in the AMI group. In addition, the expression levels of antioxidant enzymes (MnSOD) and SERCA2 were improved in the AMI with PF resection compared with those in the AMI group.
Conclusion
Surgical resection of PF might ameliorate myocardial mitochondria dysfunction in obese AMI.

Keyword

Acute Myocardial Infarction; Heart Failure; Pericardial Fat; Surgical Resection

Figure

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  Fig. 1 The comparison of cardiac function between AMI and AMI with PF resection. EF was measured by echocardiography. Values are expressed as mean ± standard deviation.AMI = acute myocardial infarction, PF = pericardial fat, EF = ejection fraction.*P < 0.05.

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  Fig. 2 The electron microscopic image of the mitochondria in the peri-infarction area between AMI and AMI with PF resection. (A) AMI; (B) AMI with PF resection. Transmission electron microscopic images (×3,000; scale bar 1,000 nm) in the myocardia.AMI = acute myocardial infarction, PF = pericardial fat.

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  Fig. 3 The comparison of OXPHOS subunit mRNA expression between AMI and AMI with epicardial adipose resection. mRNA expression levels of the following OXPHOS subunits are depicted; NDUFB3 of complex I (A); NDUFB5 of complex I (B); SDHB of complex II (C). Representative blots for OXPHOS subunit: NDUFB5 level (D). Values are expressed as mean ± standard deviation.OXPHOS = oxidative phosphorylation system, AMI = acute myocardial infarction, NDUFB = NADH dehydrogenase (ubiquinone) 1 beta subcomplex, SDHB = succinate dehydrogenase B subunit, PF = pericardial fat.*P < 0.05 vs. control; #P < 0.05 vs. AMI.

• 

  Fig. 4 The comparison of anti-oxidant enzyme and SERCA2 mRNA expression between AMI and AMI with PF resection. (A) MnSOD; (B) SERCA2. Values are expressed as mean ± standard deviation.SERCA2 = sarcoplasmic reticulum Ca2+ ATPase 2, AMI = acute myocardial infarction, MnSOD = manganese superoxide dismutase, PF = pericardial fat, GAPDH = glyceraldehyde-3-phosphate dehydrogenase.*P < 0.05 vs. control; #P < 0.05 vs. AMI.

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  Fig. 5 The comparison of ATP and PGC1-α level in the myocardia between AMI and AMI with pericardial fat resection. (A) relative cellular ATP level; (B) Representative blots of PGC1-α protein. Values are expressed as mean ± standard deviation.ATP = adenosine triphosphate, PGC1-α = peroxisome-proliferator-activated receptor γ, co-activator-1α, AMI = acute myocardial infarction, PF = pericardial fat.*P < 0.05 vs. control.

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