Table 3.
Proteins identified in human and porcine LV biopsies with a difference in FDR-based statistical analysis and their role in myocardial ischemia/reperfusion and in cardioprotection.
| human LV biopsies | ||||||
|---|---|---|---|---|---|---|
| protein | higher expression with | cellular localization | function | species/model | role in myocardial ischemia/reperfusion | role in cardioprotection |
| prostaglandin reductase 2 | RIPC at early reperfusion | cytoplasm | - catalyzes the reaction of essentially inactive 15-keto- prostaglandin E2 to the active 15-keto-13,14-dihydro-prostaglandin E2 | pigs/ isolated perfused rat hearts | — | -pharmacological inhibition of prostaglandin synthesis abrogated the cardioprotection by local ischemic preconditioning/postconditioning61 |
| porcine LV biopsies | ||||||
| protein, phosphorylation site | higher phosphorylation with | cellular localization | function | species/model | role in myocardial ischemia/reperfusion | role in cardioprotection |
| α-crystallin B, ser59 | RIPC at early reperfusion | cytoplasm, nucleus, mitochondria | - heat shock protein with chaperone-like activity | pigs | -decreased α-crystallin B expression after 90/120 min ischemia/reperfusion | -preserved α-crystallin B expression with ischemic postconditioning62 |
| -prevents aggregation of various proteins under stress conditions | mice | -increased α-crystallin B phosphorylation (at Ser59) and expression in myofibrils and in mitochondria after 25/10 min ischemia/reperfusion | -infarct size reduction by α-crystallin B peptide administration62 | |||
| rat ventricular cardiomyocytes | — | -phosphorylation of α-crystallin B at ser59 mediates the protection in response to mitogen-activated protein kinase 663 | ||||
| BAG family molecular chaperone regulator 3 (BAG3), pro387 | RIPC at early reperfusion | cytoplasm, nucleus | -serves as cochaperone with members of the heat shock family to regulate protein quality control | neonatal mouse ventricular cardiomyocytes | -decreased BAG3 expression after 14/4 h hypoxia/reoxygenation | — |
| -interacts with Bcl-2 to inhibit apoptosis | mice | — | - infarct size reduction by infection with BAG3-expressing adenovirus64 | |||
| -maintains the structural integrity of the sarcomere by linking filaments with the Z-disc | ||||||
| calpastatin, ser222, pro244, Ile312 | sham at early reperfusion | cytosol, endoplasmic reticulum, mitochondria, membrane | -specific inhibitior of calpain, which can contribute to induction of myocardial ischemia/reperfusion injury by the generation and release of proapoptotic factors from mitochondria65 | isolated perfused rat hearts | -decreased calpastatin expression after 25/25 min ischemia/reperfusion | -altered myocardial calpain or calpastatin protein levels not associated with exercise-induced infarct size reduction66 |
| -involved in muscle protein degradation in living tissue | isolated perfused rat hearts | -decreased calpastatin expression after 30/120 min ischemia/reperfusion | -preserved calpastatin expression with cardioprotection by berbamine67 | |||
| desmin, ser45 | sham at early reperfusion | cytoplasm, cell membrane | -muscle-specific, intermediate filament | isolated perfused rat hearts | -decreased desmin expression after 30/120 min ischemia/reperfusion | -preserved desmin expression with cardioprotection by berbamine67 |
| -integrates the sarcolemma, Z disk, and nuclear membrane in sarcomeres | ||||||
| -regulates sarcomere architecture | ||||||
| galectin 3, ser25 | RIPC/sham at early reperfusion | cytoplasm, nucleus, mitochondria | -pleiotropic lectin | mice | - increased galactin 3 gene expression after 30 min/7 d ischemia/reperfusion68 | — |
| -involved in cell adhesion, cell activation and chemoattraction, cell growth and differentiation, cell cycle, and apoptosis | ||||||
| MICOS complex subunit MIC60, met88 | sham at baseline | membrane, mitochondria | -maintains crista junctions, inner membrane architecture | isolated perfused rat hearts | — | -increased MICOS complex subunit Mic60expression, when protection by ischemic postconditioning abrogated by mitoKATP blockade69 |
| mitogen-activated protein kinase 3/mitogen-activated protein kinase 1 (ERK1/2), lys134/ile90, pro152 | RIPC at early reperfusion | cytoplasm, nucleus, mitochondria | -protein-serine/threonine kinases that participate in the Ras-Raf-MEK-ERK signal transduction cascade | isolated perfused rat hearts | -decreased phosphorylation of ERK1/2 at thr202/tyr204 after 30/120 min ischemia/reperfusion | -phosphorylation of ERK1/2 at thr202/tyr204 causally involved in cardioprotection by RIPC28 |
| -involved in cell adhesion, cell cycle progression, cell migration, cell survival, differentiation, metabolism, proliferation, and transcription | pigs/patients | -increased phosphorylation of ERK1/2 at thr202/tyr204 after ischemia/reperfusion | -phosphorylation of ERK1/2 at thr202/tyr204 not associated with cardioprotection by RIPC26, 28 | |||
| -central component of the reperfusion injury salvage kinase (RISK) pathway70 | ||||||
| nexilin, Lys16, Ser80, Lys300, ile364/lys248, ile312 | sham at baseline/early reperfusion | cytoplasm, cytoskeleton | -filamentous actin-binding protein | neonatal rat ventricular cardiomyocytes | -decreased nexilin expression after 2/3 h hypoxia/reoxygenation71 | — |
| -involved cell adhesion and migration | ||||||
| sequestosome-1 (p62), thr269/ser272 | sham at early reperfusion | cytoplasm, endoplasmic reticulum, endosomes, lysosomes, nucleus, mitochondria | -autophagosome cargo protein | isolated perfused rat hearts | - increased p62 expression after 30/30 min ischemia/reperfusion | -decreased expression of p62 by ischemic preconditioning72 |
| - targets other proteins for selective autophagy | - p62 recruitment to mitochondria associated with infarct size reduction by ischemic preconditioning73 | |||||
| -decrease of p62 expression is associated with activation of autophagy | patients | -expression did not change after early reperfusion | - p62 expression not different between RIPC and sham27 | |||
| sodium/potassium-transporting ATPase subunit α, val15, ser16 | sham at early reperfusion | cell membrane, membrane | - catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane | isolated perfused rat hearts | - decreased activity and expression after 45/20-40 min ischemia/reperfusion74 | — |
| xin actin-binding repeat-containing protein 1, ser205 | sham at early reperfusion | cell junction | - protects actin filaments during depolymerization | isolated perfused mice hearts | - upregulated gene expression after 25/45 min ischemia/reperfusion75 | — |