Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0018801 (
heart failure
)
72,216
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Heart failure
is associated with mitochondrial dysfunction so that restoring or improving mitochondrial health is of therapeutic importance. Recently, reduction in NAD
+
levels and NAD
+
-mediated deacetylase activity has been recognized as negative regulators of mitochondrial function. Using a cardiac specific KLF4 deficient mouse line that is sensitive to stress, we found mitochondrial protein hyperacetylation coupled with reduced Sirt3 and NAD
+
levels in the heart before stress, suggesting that the KLF4-deficient heart is predisposed to NAD
+
-associated defects. Further, we demonstrated that short-term administration of
Nicotinamide Mononucleotide
(
NMN
) successfully protected the mutant mice from pressure overload-induced
heart failure
. Mechanically, we showed that
NMN
preserved mitochondrial ultrastructure, reduced ROS and prevented cell death in the heart. In cultured cardiomyocytes,
NMN
treatment significantly increased long-chain fatty acid oxidation despite no direct effect on pyruvate oxidation. Collectively, these results provide cogent evidence that hyperacetylation of mitochondrial proteins is critical in the pathogenesis of cardiac disease and that administration of
NMN
may serve as a promising therapy.
...
PMID:Short-term administration of Nicotinamide Mononucleotide preserves cardiac mitochondrial homeostasis and prevents heart failure. 2888 80
