Protein acylation and heart failure: A review of novel lysine modifications in cardiac pathology

Table 2 Summary of novel lysine acylations and pathological cardiac hypertrophy and heart failure

Novel lysine acylations	Models	Sites	Specific functions	Refs.
Crotonylation	Mice	TMP1 K28/29cr; IDH3α K199cr	TMP1 K28/29 and IDH3α K199cr are decreased in a model of cardiac dysfunction induced by ischemia-reperfusion	[53]
Crotonylation	Human; mice	H3K18cr, H2BK12cr	H3K18cr and H2BK12cr are elevated in hypertrophic cardiomyopathy	[54]
Crotonylation	Mice	NAE1 K238cr	NAE1 K238cr increases in the cardiac hypertrophy model	[55]
Crotonylation	Mice	SERCA2a K120cr	SERCA2a K120cr is significantly elevated in SIRT1 knockout mice, which impairs SERCA2a activity and leads to alterations in energy metabolism that precipitate cardiac hypertrophy and dysfunction	[56]
Lactylation	Mice	α-MHC K1897 La	α-MHC K1897 La reduction in heart failure weakens its interaction with titin, ultimately resulting in severe HF	[48]
Lactylation	Mice	H3K18 La	The elevation of H3K18 La is associated with pathological myocardial hypertrophy and cardiac dysfunction	[59]
Lactylation	Mice	H3K56 La	H3K56 La is reduced in the Mi/R model, and the inhibition of H3K56 La negated the cardioprotective effects of HSPA12A	[60]
Lactylation	Mice	H3K18 La	Exercise training enhances cardiac function by inhibiting YTHDF2, which reduces H3K18 lactylation and mitigates myocardial ischemia-reperfusion injury	[61]
Lactylation	Mice	Snail1	The lactylation of Snail1 was elevated following myocardial infarction, which contributed to myocardial fibrosis and worsened cardiac dysfunction	[62]
Succinylation	Mice	ECHA K351succ	SIRT5 mediates the desuccinylation of ECHA K351, thereby improving cardiac metabolism and function and reducing myocardial hypertrophy	[71]
Succinylation	Mice	IDH2	The inhibition of SIRT5 expression results in increased succinylation of IDH2, which disrupts mitochondrial homeostasis and contributes to myocardial fibrosis and HF	[72]
Succinylation	Human; mice	CPT2 K424succ	SIRT5 mediates the desuccinylation of CPT2 K424 in diabetic cardiomyopathy, thereby ameliorating lipid deposition, myocardial hypertrophy, and diastolic dysfunction	[73]
Succinylation	Mice	Txnrd1 K534succ	Txnrd1 K534succ increase in mice with a knockout of LDHA, leading to severe cardiac dysfunction in a pressure overload mouse model	[74]
β-hydroxybutyr-ylation	Mice	CS K395bhb	β-hydroxybutyrate mitigates heart failure with preserved ejection fraction by activating CS through the enhancement of CS K395bhb	[82]
Propionylation	Mice	H3K23pr	H3K23pr increase in cardiac hypertrophy and HF	[86]
Butyrylation	Mice	H3K9bu	H3K9bu is diminished due to the downregulation of β-oxidase in the heart following TAC surgery	[90]
Malonylation	Rat	VDAC2 K46mal	VDAC2 K46mal was elevated in mice with sepsis-induced cardiac dysfunction	[97]
Malonylation	Mice	GSTP1 K121mal	The abnormal decrease of SIRT5 increase of GSTP1 K121mal in DCM leads to oxidative stress and mitochondrial dysfunction	[98]
Malonylation	Mice	Ago2 K440mal	The increase of AGO2 K440mal enhances the production of ROS in mitochondria, subsequently impairing cardiac function in DCM	[99]
2-hydroxyisobu-tyrylation	Mice	DLD K440hib	DLD K440hib increase in the TAC-induced cardiac hypertrophy model	[105]

AGO2: Argonaute 2; CPT2: Carnitine palmitoyltransferase 2; CS: Citrate synthase; DCM: Diabetic cardiomyopathy; ECHA: E-CoA hydratase α subunit; GSTP1: Glutathione S-transferase 1; HF: Heart failure; HSPA12A: Heat shock protein family A member 12A; IDH: Isocitrate dehydrogenase; LDHA: Lactate dehydrogenase A; α-MHC: Α-myosin heavy chain; NAE1: NEDD8-activating enzyme E1 regulatory subunit; ROS: Reactive oxygen species; SERCA2a: Sarco/endoplasmic reticulum calcium ATPase 2a; SIRT: Sirtuin; Txnrd1: Thioredoxin reductase 1; VDAC2: Voltage-dependent anion-selective channel protein 2; YTHDF2: YT521-B homology domain family member 2; TAC: Transverse aortic constriction.