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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