Table 1.
Therapeutic peptides used in different IR animal models mentioned in this review.
| Peptides | Other names | Experimental models | Administration | Species | Mechanisms | References |
|---|---|---|---|---|---|---|
| MITOCHONDRIA-DEPENDENT APOPTOSIS | ||||||
| Cyclosporine A | Ciclosporine A, CsA, CycloMulsion, Sandimmune |
in vivo 30 min I/3 h R | 10 mg/kg, i.v.−5 min before R | Rabbit | Reduced IS | (51) |
| in vivo 30 min I/2 h R | 10 mg/kg, i.v.—at the onset of R | Mouse | Reduced IS | (52) | ||
| in vivo 25 min I/2 h R | 5 mg/kg, i.v.−5 min before R | Rat | Reduced IS | (53) | ||
| in vivo 90 min H/2 h R | 5 mg/kg, i.v.−5 min before R | Pig | Reduced IS | (54) | ||
| in vivo 40 min I/3 h R | 10 mg/kg, i.v.−5 min before R | Pig | No reduction in IS | (55) | ||
| in vivo 45 min I/2 h R | 10 mg/kg, i.v.−3 min before R | Pig | No reduction in IS | (56) | ||
| in vivo 40 min I/4 h R | 2.5 mg/kg, i.v.−7 min before R | Pig | No reduction in IS | (57) | ||
| in vivo 60 min I/3 h R | 10 mg/kg, i.v.−15-10 min before R | Pig | Reduced IS and microvesicular damage, better LV function |
(58) | ||
| Elamipretide | SS-31, MTP-131, Bendavia |
ex vivo 30 min global I/3 h R | 1 μmol/L—during the whole R | Guinea pig | Improved contractile force, increased heart beating rates |
(59) |
| ex vivo 20 min global I/2 h R | post-ischemic administration 1 nM during R | Guinea pig | Reduced IS | (60) | ||
| in vivo 30 min I/180 min R | at the onset of R−0.10 mg/kg/h i.v. during 20 min then 0.05 mg/kg h i.v. during 160 min | Rabbit | No significant effect on IS |
|||
| in vivo 60 min I/180 min R | 0.05 mg/kg/h i.v.—during the 30 min before R | Sheep | Reduced IS, protection against the no-reflow phenomenon |
|||
| ex vivo 20 min global I/120 min R | 10 μmol/L i.v.—at the onset of R | Rat | Improve mitochondria function by aggregating cardiolipin |
(61) | ||
| Humanin | S14G-humanin | in vivo 45 min I/24 h R | 2 mg/kg i.c.—at the onset of R | Mouse | Reduced IS and increased EF |
(62) |
| in vivo 30 min I/2 h R | 252 μg/kg i.v.−15 min before R | Rat | Reduced IS, arrhythmia, and cardiac mitochondrial dysfunction |
(63) | ||
| in vivo 60 min I/48 h R | 2 mg/kg i.v.−10 min before R | Pig | Reduced IS | (64) | ||
| Tat-BH4 | / | in vivo 40 min I/24 h R | 1 mg/kg i.v.—at the onset of R | Mouse | Reduced IS and apoptosis |
(65) |
| Tat-V1-Cal | / | in vivo 30 min I/2 h R | 1 mg/kg i.v.−5 min before R | Rat | Reduced IS | (66) |
| AID-Tat | / | in vivo 30 min I/12 weeks R | 10 μmol/L i.c.—at the onset of R | Rat | Reduced IS and supported contractility |
(67) |
| RECEPTOR-DEPENDENT APOPTOSIS | ||||||
| Tat-DAXXp | TD | in vivo 40 min I/24 h R | 1 mg/kg i.v.—at the onset of R | Mouse | Reduced IS and apoptosis |
(26) |
| in vivo 40 min I/6 months R | 1 mg/kg i.v.—at the onset of R | Mouse | Reduced fibrosis, increase EF |
(27) | ||
| Tat-FADDp | TF | in vivo 40 min I/24 h R | 1 mg/kg i.v.—at the onset of R | Mouse | Reduced IS and apoptosis |
(68) |
| INFLAMMATION | ||||||
| ANP | ANP1-28 | ex vivo 15 min I/15 min R | 0.1 μmol/L—at the onset of R | Rat | Better cardiac and corona flow recovery |
(69) |
| Carperitide | in vivo 60 min I/6 h R | 0.2 μg/kg/min i.v.−15 min after I till the end of R | Dog | Reduced IS, increased blood flow, decreased left ventricular systolic pressure, and end-diastolic pressure |
(70) | |
| in vivo 90 min I/6 h R | 0.1 μg/kg/min i.v.−10 min before I till 1 h of R | Dog | Reduced IS | (71) | ||
| Urodilatin (URO) | ex vivo 40 min I/1 h R | 0.05 μmol/L—first 15 min of R | Rat | Higher LV pressure | (72) | |
| in vivo 47 min I/2 h R | 10 ng/kg/min i.v.—during the first 25 min of R | Pig | Reduced IS | |||
| BNP | / | ex vivo 30 min I/90 min R | 10 nmol/L−5 min before R till 15 min of R | Rat | Reduced IS | (73) |
| / | in vivo 30 min I/4 h R | 0.03μg/kg min i.v.−15 min before R till the end of R | Rat | Reduced IS, decreased LDH, and CK levels |
(74) | |
| RhBPN | in vivo 40 min I/24 h R | 0.035 mg i.p.—after IR one injection/d for 3 d | Mice | Reduced IS and CD4+T cell proliferation |
(75) | |
| DNP | Lebetin 2 (L2) | ex vivo 30 min I/90 min R | 200 nmol/L−5 min before R till 15 min of R | Rat | Reduced IS | (73) |
| in vivo 30 min I/2 h R | 100 ng/g i.p.−5 min before R | Mouse | Reduced IS | (76) | ||
| in vivo 35min I/2 d or 14 d R | 25 ng/g i.p.−5 min before R | Rat | Reduced IS, collagen content, and enhanced M2-like macrophages |
|||
| CNP | / | ex vivo 25 min I/2 h R | 30 nmol/L—during the first 30 min of R | Rat | Reduced IS and coronary perfusion pressure (CPP) |
(77) |
| VNP | Vasonatrin | in vivo 30 min I/4 h or 6 h R | 100 μg/kg, i.v.−10 min before R | Rat | Reduced IS, Reduced LV systolic and end-diastolic pressure |
(78) |
| Ac2-26 | N-terminus of Annexin-1 | in vivo 25 min I/2 h R | 1 mg/kg i.v.—at the onset of R | Rat | Reduced IS, Myeloperoxidase (MPO) activity, and IL-1b levels |
(79) |
| in vivo 40 min I/24 h R | 1 mg/kg i.v.—at the onset of R | Mouse | Reduced IS, cTnI (24 hR), inflammation (48 h R), fibrosis, and apoptosis (7-days R) |
(80) | ||
| AnxA12−50 | in vivo 25 min I/2 h R | 5 μg/mouse i.v.—at the onset of R | Mouse | Reduced IS and plasma levels of cTnI, CCL5, ILβ |
(81) | |
| CR-AnxA12−50 | ||||||
| CR-AnxA12−48 | in vivo 25 min I/2 h R | 5 μg/mouse i.v.—at the onset of R | Mouse | Reduced IS and plasma CCL5 concentration |
(82) | |
| CGEN-855A | / | in vivo 25 min I/2 h R | 2 mg/kg i.v.—immediately after R | Mouse | Reduced IS, cTnI and PMN |
(83) |
| in vivo 30 min I/3 h R | 2 mg/kg i.v.−5 min before R | Rat | ||||
| DS-IkL | / | in vivo 45 min I/24 h R | 30 μM 100 μL i.v.—immediately after R | Mouse | Reduced IS and cTnI concentration |
(84) |
| Ghrelin | / | ex vivo 30 min global I/30 min R | 10,000 pM—during R | Rat | Increased coronary flow, heart rate, left ventricular systolic pressure and left ventricular end-diastolic pressure |
(85) |
| in vivo 30 min I/24 h R | 8 nmol/kg i.v.—at the onset of R | Rat | Reduced IS, inhibition of the TLR4, NLRP3, and Caspase-1 expression |
(86) | ||
| Obestatin | / | in vivo 30 min I/24 h R | 50 nM/kg—LV injection at the R | Rat | Reduced IS | (87) |
| ex vivo 30 min I/2 h R | 75 nM—during the first 20 min of R | Rat | Reduced IS | (88) | ||
| NECROPTOSIS | ||||||
| Nesfatin-1 | / | in vivo 30 min I/24 h R | 20 μg/kg i.p.—prior R | Rat | Reduced IS and EF, Reduced Beclin-1 and Caspase-3 expression |
(89) |
| in vivo 30 min I/24 h R | 20 μg/kg i.p.—prior R | Rat | Reduced expression of RIPK1, RIPK3, MLKL, ROCK1, and ROCK2 proteins |
(90) | ||
| in vivo 30 min I/2 h R | 100 pmol/L—during the first 20 min of R | Rat | Reduced IS, ERK1/2 activation |
(91) | ||
| AUTOPHAGY | ||||||
| HBSP | Helix B surface peptide | in vivo 45 min I/2 h R | 90 μg/kg, i.p.−5 min before R | Mouse | Reduced IS, decreased cardiomyocyte apoptosis |
(92) |
| OTHERS | ||||||
| GLP-1 | Glucagon-like peptide 1; [GLP-1(7–36)amide]; Exenatide | ex vivo 45 min global I/2 h R | 0.3 nM—at the onset of R | Rat | Improve LV pressure, no effect on IS |
(93) |
| in vivo 30 min I/2 h R | 4.8 pmol/kg/min—perfusion during the procedure | Rat | Reduced IS | (94) | ||
| Apelin-13/-36 | / | ex vivo 35 min global I/35 min R | 1,000 nM Apelin-13/1,000 nM Apelin-36—at the onset of R | Rat | Reduced IS (Apelin-13 = 40%/Apelin-36 = 26%) |
(14) |
| in vivo 30 min I/120 min R | 0.1 mg/kg Apelin-13/0.27 mg/kg Apelin-36, i.v.—at the onset of R | Mouse | Reduced IS (Apelin 13 = 43%/Apelin 36 = 33%) |
|||
| Apelin-13 | / | in vivo 45 min regional I/24 h R | 0.1 μg/kg—at 5 min after R | Mouse | Reduced IS, decreased apoptosis |
(95) |
| Elabela | Apela; Toddler | in vivo 30 min regional I/4 h R | 0.7 mg/kg, i.v.—at 5 min of R | Rat | Decreased apoptosis, fibrosis, and oxidative stress |
(96) |
H, hypoxia; I, ischemia; R, reperfusion; i.p, intra peritoneal injection; i.v, intra venous injection; i.c., intra coronary injection; IS, infarct size; LV, left ventricle.