Do platelets protect the heart against ischemia/reperfusion injury or exacerbate cardiac ischemia/reperfusion injury? The role of PDGF, VEGF, and PAF.

BACKGROUND: Acute myocardial infarction (AMI) is one of the main causes of death. It is quite obvious that there is an urgent need to develop new approaches for treatment of AMI. OBJECTIVE: This review analyzes data on the role of platelets in the regulation of cardiac tolerance to ischemia/reperfusion (I/R). METHODS: It was performed a search of topical articles using PubMed databases. FINDINGS: Platelets activated by a cholesterol-enriched diet, thrombin, and myocardial ischemia exacerbate I/R injury of the heart. The P2Y12 receptor antagonists, remote ischemic postconditioning and conditioning alter the properties of platelets. Platelets acquire the ability to increase cardiac tolerance to I/R. Platelet-derived growth factors (PDGFs) increase tolerance of cardiomyocytes and endothelial cells to I/R. PDGF receptors (PDGFRs) were found in cardiomyocytes and endothelial cells. PDGFs decrease infarct size and partially abrogate adverse postinfarction remodeling. Protein kinase C, phosphoinositide 3-kinase, and Akt involved in the cytoprotective effect of PDGFs. Vascular endothelial growth factor increased cardiac tolerance to I/R and alleviated adverse postinfarction remodeling. The platelet-activating factor (PAF) receptor inhibitors increase cardiac tolerance to I/R in vivo. PAF enhances cardiac tolerance to I/R in vitro. It is possible that PAF receptor inhibitors could protect the heart by blocking PAF receptor localized outside the heart. PAF protects the heart through activation of PAF receptor localized in cardiomyocytes or endothelial cells. Reactive oxygen species and kinases are involved in the cardioprotective effect of PAF. CONCLUSION: Platelets play an important role in the regulation of cardiac tolerance to I/R.

Ferroptosis, a Regulated Form of Cell Death, as a Target for the Development of Novel Drugs Preventing Ischemia/Reperfusion of Cardiac Injury, Cardiomyopathy and Stress-Induced Cardiac Injury.

The hospital mortality in patients with ST-segment elevation myocardial infarction (STEMI) is about 6% and has not decreased in recent years. The leading cause of death of these patients is ischemia/reperfusion (I/R) cardiac injury. It is quite obvious that there is an urgent need to create new drugs for the treatment of STEMI based on knowledge about the pathogenesis of I/R cardiac injury, in particular, based on knowledge about the molecular mechanism of ferroptosis. In this study, it was demonstrated that ferroptosis is involved in the development of I/R cardiac injury, antitumor drug-induced cardiomyopathy, diabetic cardiomyopathy, septic cardiomyopathy, and inflammation. There is indirect evidence that ferroptosis participates in stress-induced cardiac injury. The activation of AMPK, PKC, ERK1/2, PI3K, and Akt prevents myocardial ferroptosis. The inhibition of HO-1 alleviates myocardial ferroptosis. The roles of GSK-3ß and NOS in the regulation of ferroptosis require further study. The stimulation of Nrf2, STAT3 prevents ferroptosis. The activation of TLR4 and NF-κB promotes ferroptosis of cardiomyocytes. MiR-450b-5p and miR-210-3p can increase the tolerance of cardiomyocytes to hypoxia/reoxygenation through the inhibition of ferroptosis. Circ_0091761 RNA, miR-214-3p, miR-199a-5p, miR-208a/b, miR-375-3p, miR-26b-5p and miR-15a-5p can aggravate myocardial ferroptosis.

SCAI Staging Application for Acute Myocardial Infarction-Related Cardiogenic Shock at a Single-Center Russian Registry.

AIM: To access the features of the course of myocardial infarction (MI) in patients with different stages of MI complicated by cardiogenic shock (MI CS) according to the SCAI scale. METHODS: We retrospectively described the portrait of CS MI (n = 117) at different stages of SCAI from the hospital MI registry (n = 1253). RESULTS: Hospital mortality increased from stage to stage (p ≤ 0.001). Significant differences in biochemical parameters were found both for indicators characterizing intensive care measures, such as the presence of mechanical lung ventilation or an intra-aortic balloon pump, and for indicators of organ hypoperfusion such as lactate level, pHv (7.39 (7.36; 7.44) at stage A-B; 7.14 (7.06; 7.18) at stage E), creatinine, and glomerular filtration rate. Parameters related to MI characteristics, such as instrumental and laboratory data, anamnesis of ischemia, and performed treatment, did not differ between groups. Polynomial logistic regression showed that lactate level, mechanical ventilation, and monocyte count upon admission (1.15 (0.96; 1.23) at stage A-B; 0.78 (0.49; 0.94) at stage E, p = 0.005) correlated with CS severity. CONCLUSION: The characteristics of MI at different stages of SCAI do not have differences and do not determine the severity of shock. We revealed a high discriminatory potential of the pH level in predicting refractory shock. The value of monocytes at admission may be a promising predictor of the severity of MI CS. The question of the causes of heterogeneity of MI CS, taking into account the homogeneity of MI characteristics, remains open and promising.