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Table 1 Summary of cell death in experimental models of chronic MI

From: Targeting necroptosis as therapeutic potential in chronic myocardial infarction

Study model

Methods

Necroptosis

Apoptosis

Autophagy

References

H9c2 cells

OGD for 24 h

(16% CO2, < 0.1% O2)

↑ (3 h)

↓ (after 3 h)

↑ (6 h)

↓ (after 6 h)

↑ (3 h)

↓ (after 3 h)

[29]

H9c2 cells

OGD for 24 h

(5% CO2, 94% N2, 1% O2)

↑

N/A

↓

[34]

 

OGD for 24 h

(5% CO2, 94% N2, 1% O2)

 + Alliin: 25, 100, 200 μg/ml (pre-treatment)

↓

↓

↑

 

H9c2 cells

OGD for 24 h

(5% CO2, 94% N2, 1% O2)

↑

N/A

↑ (3 h)

↓ (after 6 h)

[21]

 

OGD + RIPK3 overexpression

↑

N/A

N/A

 
 

OGD + RIPK3 knockdown

↓

N/A

N/A

 
 

OGD + Beclin1 overexpression

↓

N/A

↑

 
 

OGD + Beclin1 knockdown

↑

N/A

↓

 

NRVCM cells

TNFα + zVAD

↑

N/A

N/A

[33]

MEFs cells

TNFα + Traf2−/−

↑

N/A

N/A

[30]

 

TNFα + shTraf2

↑

N/A

N/A

 
 

TNFα + shTraf2 + zVAD

↔

N/A

N/A

 
 

TNFα + shTraf2 + Nec-1

↓

N/A

N/A

 
 

TNFα + Ad-Traf2WT

↓

N/A

N/A

 
 

TNFα + Ad-Traf2ΔR

↑

N/A

N/A

 
 

TNFα + Ad-Traf2ΔR + zVAD

↔

N/A

N/A

 
 

TNFα + Ad-Traf2ΔR + zVAD + Ad-shTRADD

↓

N/A

N/A

 
 

TNFα + AdTraf2ΔR + Ad-TAK1ΔN + zVAD

↓

N/A

N/A

 
 

TNFα + AdTraf2ΔR + AdshRIPK3 + zVAD

↓

N/A

N/A

 
 

TNFα + AdTraf2ΔR + shMLKL + zVAD

↓

N/A

N/A

 
 

TNFα + Traf2−/− + zVAD

↔

N/A

N/A

 
 

TNFα + Traf2−/− + Nec-1

↓

N/A

N/A

 
 

TNFα + Ad-Traf2ΔR + Nec1

↓

N/A

N/A

 

Isolated cardiomyocytes

Hypoxic conditions for 72 h

(95% N2, 5% CO2, 0% O2)

↑

N/A

N/A

[31]

 

Hypoxic conditions + agomiR-325-3p

 + Z-IETD-FMK

↑

N/A

N/A

 
 

Hypoxic conditions + antagomiR-325-3p

 + Z-IETD-FMK

↑

N/A

N/A

 
 

Hypoxic conditions + siRIPK3 + agomiR

 + Z-IETD- FMK

↑

N/A

N/A

 
 

Hypoxic conditions + siRIPK3 + antagomir

 + Z-IETD-FMK

↔

N/A

N/A

 

Cardiac myofibroblasts

sCD74

(0, 0.04, 0.16, 8, 16, 40 nmol/L) + rMIF (8 nmol/L) for 24 h

↑

↔

N/A

[77]

SD rats

Permanent LAD ligation for 4 weeks

↑

↑

↑

[29]

C57BL/6 mice

Permanent LAD ligation for 2 weeks

↑

↑

N/A

[34]

 

Permanent LAD ligation for 2 weeks

 + Alliin: 100 mg/kg IP for 7 days (pre-treatment)

↓

↓

↑

 

RIPK3−/− mice

Permanent LAD ligation for 4 weeks

↓

N/A

N/A

[33]

C57BL/6 mice

Permanent LAD ligation for 12 weeks

↑

N/A

↑ (1–3 day)

↓ (after 1 week)

[21]

 

Permanent LAD ligation for 12 weeks + RIPK3 knockdown

↓

N/A

N/A

 
 

Permanent LAD ligation for 12 weeks + RIPK3 overexpression

↑

N/A

N/A

 
 

Permanent LAD ligation for 12 weeks + Beclin1 knockdown

↑

N/A

↓

 
 

Permanent LAD ligation for 12 weeks + Beclin1 overexpression

↓

N/A

↑

 

C57BL/6 J mice

Permanent LAD ligation

↑

↑

N/A

[31]

 

Permanent LAD ligation + Antagomir- 325-3p

↑

↑

N/A

 
 

Permanent LAD ligation + AgomiR- 325-3p

↓

↓

N/A

 

Genetically modified mouse models

Traf2fl/fl-αMHC-Cre

↑

↑

N/A

[30]

 

Traf2fl/fl- βMHC-Cre (Traf2 deficient)

↑

N/A

N/A

 
 

RIPK3−/− + Traf2fl/fl-αMHC-Cre

↓

↑

N/A

 
 

Permanent LAD ligation for 2 weeks + Traf2fl/ + αMHC-Cre

↑

↑

N/A

 

CAD patients

Plasma/serum collected from patient (SCAD, UA, MI)

↑

N/A

N/A

[26]

Patients with HF

Peripheral venous blood samples

↑

N/A

N/A

[38]

Patients with HF

LV samples (CAD)

↑

↔

N/A

[64]

 

LV samples (DCM)

↑

↔

N/A

 

Patients with HF

LV samples (CAD and DCM)

↑

↑

↑

[63]

  1. CAD, coronary artery disease; DCM, dilated cardiomyopathy; HF, heart failure; IP, intraperitoneal injection; LAD, left anterior descending coronary artery; LV, left ventricle; MEF, mouse embryonic fibroblast; MI, myocardial infarction; MLKL, mixed lineage kinase domain like pseudokinase; N/A, not available; Nec-1, necrostatin 1; NRVCM, neonatal rat ventricular cardiomyocyte; OGD, oxygen–glucose deprivation; RIPK3, receptor-interacting serine/threonine-protein kinase 3; RIPK3−/−, receptor-interacting serine/threonine-protein kinase 3 gene knockout; SCAD, stable coronary artery disease; SD, Sprague Dawley; TNFα, tumor necrosis factor alpha; TRADD, tumor necrosis factor receptor type 1-associated DEATH domain protein; Traf2, tumor necrosis factor receptor-associated factor 2; Traft2−/−, tumor necrosis factor receptor-associated factor 2 gene knock out; UA, unstable angina; Z-IETD-FMK, caspase 8 inhibitor; zVAD, pan Caspase Inhibitor Z-VAD-FMK; Z-IETD-FM, caspase 8 inhibitor-Z-IE(OMe)TD(Ome)-FMK