Macrophage activation and polarization in post-infarction cardiac remodeling.

Adverse cardiac remodeling leads to impaired ventricular function and heart failure, remaining a major cause of mortality and morbidity in patients with acute myocardial infarction. It have been shown that, even if all the recommended therapies for ST-segment elevation myocardial infarction are performed, one third of patients undergoes progressive cardiac remodeling that represents morphological basis for following heart failure. The need to extend our knowledge about factors leading to different clinical scenarios of myocardial infarction and following complications has resulted in a research of immuno-inflammatory pathways and molecular activities as the basis for post-infarction remodeling. Recently, macrophages (cells of the innate immune system) have become a subject of scientific interest under both normal and pathological conditions. Macrophages, besides their role in host protection and tissue homeostasis, play an important role in pathophysiological processes induced by myocardial infarction. In this article we summarize data about the function of monocytes and macrophages plasticity in myocardial infarction and outline potential role of these cells as effective targets to control processes of inflammation, cardiac remodeling and healing following acute coronary event.

Macrophages of the Cardiorenal Axis and Myocardial Infarction.

The aim of our study was to compare the features of macrophage (mf) composition of the kidneys in patients with fatal myocardial infarction (MI) and in patients without cardiovascular diseases (CVD). We used kidney fragments taken during autopsy. Macrophage infiltration was assessed by immunohistochemistry: antibodies CD68 were used as a common mf marker, CD80-M1 type mf marker, CD163, CD206, and stabilin-1-M2 type. Macrophage composition of the kidneys in patients with fatal MI was characterized by the predominance of CD163+ cells among studied cells, and the control group was characterized by the predominance of CD163+, CD206+, and CD68+. In patients with MI, biphasic response from kidney cells was characterized for CD80+ and CD206+: their number decreased by the long-term period of MI; other cells did not show any dynamics. The exact number of CD80+ cells in kidneys of individuals without CVD was slightly higher than in patients with MI, and the number of CD206+-strikingly predominant. Subsequent analysis of CD80+ and CD206+ cells in a larger sample, as well as comparison of data with results obtained from survivors of MI, may bring us closer to understanding whether the influence on these cells can serve as a new target in personalized therapy in postinfarction complications.

Microarray Analysis for Transcriptomic Profiling of Myocardium in Patients with Fatal Myocardial Infarction.

Transcriptomic evidence from human myocardium in myocardial infarction (MI) is still not sufficient. Thus, there is a need for studies on human cardiac samples in relation to the clinical data of patients. The purpose of our pilot study was to investigate the transcriptomic profile of myocardium in the infarct zone, in comparison to the remote myocardium, in patients with fatal MI, via microarray analysis. This study included four patients with fatal MI type 1. We selected histologically verified samples from within the infarct area (n = 4) and remote myocardium (n = 4). The whole transcriptome was evaluated using microarray analysis. Differentially expressed genes (DEGs) clustered in the infarct area and in the remote myocardium allowed their differentiation. We identified a total of 1785 DEGs (8.32%) in the infarct area, including 1692 up-regulated (94.79%) and 93 down-regulated (5.21%) genes. The top 10 up-regulated genes were TRAIL, SUCLA2, NAE1, PDCL3, OSBPL5, FCGR2C, SELE, CEP63, ST3GAL3 and C4orf3. In the infarct area, we found up-regulation of seventeen apoptosis-related genes, eleven necroptosis-related, and six necrosis-related genes. Transcriptome profiling of the myocardium in patients with MI remains a relevant area of research for the formation of new scientific hypotheses and a potential way to increase the translational significance of studies into myocardial infarction.

The Signaling Mechanism of Remote Postconditioning of the Heart: Prospects of the Use of Remote Postconditioning for the Treatment of Acute Myocardial Infarction.

Acute myocardial infarction (AMI) remains the leading cause of mortality in the world, highlighting an urgent need for the development of novel, more effective approaches for the treatment of AMI. Remote postconditioning (RPost) of the heart could be a useful approach. It was demonstrated that RPost triggers infarct size reduction, improves contractile function of the heart in reperfusion, mitigates apoptosis, and stimulates autophagy in animals with coronary artery occlusion and reperfusion. Endogenous opioid peptides and adenosine could be involved in RPost. It was found that kinases and NO-synthase participate in RPost. KATP channels, MPT pore, and STAT3 could be hypothetical end-effectors of RPost. Metabolic syndrome and old age abolish the cardioprotective effect of RPost in rats. The data on the efficacy of RPost in clinical practice are inconsistent. These data are discussed in the review.

Macrophages of the "Heart-Kidney" Axis: Their Dynamics and Correlations with Clinical Data and Outcomes in Patients with Myocardial Infarction.

Changes in the macrophage infiltration of kidneys in rodents under ischemic conditions may affect cardiac macrophages and lead to development of adaptive cardiac remodeling. The aim of our study was to translate experimental findings into clinically relevant applications and assess the features of macrophage infiltration of the kidney and its correlations with changes in macrophage infiltration of the myocardium and with clinical data in patients who experienced a fatal myocardial infarction (MI). We examined fragments of both organs taken from patients (n = 30) who suffered from fatal MI. Macrophage infiltration was assessed by immunohistochemistry. Macrophage infiltration of the kidneys in patients with fatal MI is heterogeneous. The early period of MI was shown to be characterized by the prevalence of CD163+ and CD68+ cells, and in the long-term period by only CD163+ cells. However, only the level of CD206+ cells in the kidneys showed the dynamics representing the late MI period. Its decrease accompanied increase in the numbers of cardiac CD68+, CD163+, CD206+, and stabilin-1+ cells in the infarct area. Kidney CD206+ cells had more correlations with cardiac macrophages than other cells, and the presence of these cells also correlated with impairment of renal function and early death.

Cardiac CD68+ and stabilin-1+ macrophages in wound healing following myocardial infarction: From experiment to clinic.

Myocardial infarction (MI) remains the leading cause of mortality and morbidity throughout the world. Macrophages are key innate immune cells that play a significant role in transition from the inflammatory to the regenerative phase during wound healing following MI. The scavenger receptor stabilin-1 is one of the most interesting macrophage biomarkers. This receptor contributes to wound healing, angiogenesis, and tissue remodeling. We suggested a research protocol using macrophage biomarkers to study the cellular basis of cardiac remodeling and healing in patients with acute MI. The purpose of the research was to translate experimental knowledge regarding macrophage subsets and their biomarkers in post-infarction myocardial regeneration into results observed in clinical settings. The study included 41 patients with fatal MI type 1. All patients were divided into four groups according to the timeline of MI histopathology. In addition to routine histopathological analysis, macrophage infiltration was assessed by immunohistochemistry. We used CD68 as a marker for the cells of the macrophage lineage and stabilin-1 as an M2-like macrophage biomarker. The number of CD68+ and stabilin-1+ macrophages in the infarct area increased and peaked in the regenerative phase and did not decrease in the late stage of MI. In the peri-infarct area, the number of CD68+ macrophages increased in the inflammatory phase, peaked during the reparative phase, and did not decrease in the late phase, while the number of stabilin-1+ macrophages increased in the regenerative phase and remained unchanged. Additionally, in the reparative phase, we observed increase in the number of CD68+ and stabilin-1+ macrophages in the non-infarct area. The research protocol suggested allowed us to translate experimental knowledge regarding macrophage subsets and their biomarkers in post-infarction myocardial regeneration into clinical data. Taken together, these results demonstrated biphasic cardiac macrophage response following acute MI somewhat similar to that in a murine model. The increase in stabilin-1+ macrophage infiltration noticed in the myocardium during the regenerative phase and the strong positive correlation between the number of these cells and timeline of MI histopathology enabled us to propose stabilin-1 as a diagnostic macrophage biomarker in myocardium wound healing in patients with acute MI.