Malonyl CoA Decarboxylase Inhibition Improves Cardiac Function Post-Myocardial Infarction

Autor: Cory S. Wagg, Jeff D. Reagan, John R. Ussher, Liyan Zhang, Kenneth Milner, Dongming M. Liu, Angela Fu, Alykhan Motani, Abhishek Gupta, Osama Abo Alrob, Chaves Mary, Nikole J. Byrne, Natasha Fillmore, Pavan K. Battiprolu, Arata Fukushima, Shaohua Wang, Gary D. Lopaschuk, Khanh Nguyen, Wei Wang, Jun Mori, Tariq R. Altamimi, Jenny Ying-Lin Lu, Jason R.B. Dyck
Rok vydání: 2018
Předmět:
0301 basic medicine
Cardiac function curve
lcsh:Diseases of the circulatory (Cardiovascular) system
CPT1
carnitine palmitoyltransferase 1
medicine.medical_specialty
TAG
triacylglycerol
heart failure
Infarction
MCD
malonyl coenzyme A decarboxylase
030204 cardiovascular system & hematology
PRECLINICAL RESEARCH
03 medical and health sciences
0302 clinical medicine
SOD
superoxide dismutase
Internal medicine
medicine
uncoupling of glycolysis
EF
ejection fraction
Trx
thioredoxin
Glycolysis
Myocardial infarction
Beta oxidation
fatty acid oxidation
FOXO3
forkhead box O3
ATGL
adipose triglyceride lipase
business.industry
glucose oxidation
Malonyl-CoA decarboxylase
medicine.disease
SPT
serine palmitoyltransferase
3. Good health
030104 developmental biology
Endocrinology
lcsh:RC666-701
Heart failure
MI
myocardial infarction
SERCA2
sarco(endo)plasmic reticulum Ca2+-ATPase 2
Cardiology and Cardiovascular Medicine
Ligation
business
Zdroj: JACC: Basic to Translational Science
JACC: Basic to Translational Science, Vol 4, Iss 3, Pp 385-400 (2019)
ISSN: 2452-302X
Popis: Visual Abstract
Highlights • MCD inhibition decreases fatty acid oxidation via increasing malonyl coenzyme A levels to prevent fatty acid uptake into mitochondria in the failing hearts induced by coronary artery ligation. • Downregulating fatty acid oxidation by MCD inhibition occurrs in conjuction with a decrease in glycolysis and in proton production while an increase in triacylglycerol biosynthesis. • MCD inhibition enhances antioxidative capacity through increasing mitochondrial superoxide dismutase activity via reducing its acetylation.
Summary Alterations in cardiac energy metabolism after a myocardial infarction contribute to the severity of heart failure (HF). Although fatty acid oxidation can be impaired in HF, it is unclear if stimulating fatty acid oxidation is a desirable approach to treat HF. Both immediate and chronic malonyl coenzyme A decarboxylase inhibition, which decreases fatty acid oxidation, improved cardiac function through enhancing cardiac efficiency in a post–myocardial infarction rat that underwent permanent left anterior descending coronary artery ligation. The beneficial effects of MCD inhibition were attributed to a decrease in proton production due to an improved coupling between glycolysis and glucose oxidation.
Databáze: OpenAIRE
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