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 “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

M2 cardiac macrophages in wound healing following myocardial infarction: translation to clinic

Funding Acknowledgements: This work was supported by the Russian Foundation for Basic Research (grant №16-04-01268

M2 cardiac macrophages in wound healing following myocardial infarction: translation to clinic

Funding Acknowledgements: This work was supported by the Russian Foundation for Basic Research (grant №16-04-01268

Cardiac macrophages in wound healing following myocardial infarction: from experiment to clinic

Introduction: Macrophages are key innate immune cells that play a significant role in transition from inflammatory to regenerative phase during wound healing following myocardial infarction (MI). Despite the progress of experimental studies devoted to the innate immune response following MI, there is no significant advancement in clinical studies. Purpose: The purpose of the research was to translate experimental knowledge regarding macrophage subsets and their biomarkers in post infarction left ventricular remodeling and myocardial regeneration into results observed in clinical settings. We suggested protocol based on usage of macrophage biomarkers to study cellular basis of cardiac remodeling and healing in patients with MI. Methods: The study included 41 patients with fatal MI type 1. All patients were divided into 4 groups depending on the timeline of MI histopathology. In addition to routine histopathological analysis macrophages infiltration was assessed by immunohistochemistry. We used CD68 as a marker for the cells of the macrophage lineage, while CD163 and stabilin-1 were considered as M2-like macrophage biomarkers. Nine patients who died from non-cardiovascular causes comprised the control group. Results: The figure (Figure 1) demonstrates results of immunohistochemical analysis. In the control group the number of CD68+ and CD163+ macrophages was lower than in the infarct, peri-infarct and non-infarct areas during all phases of MI (p < 0.001). Simultaneously the quantity of stabilin-1+ cells in the control group was higher in all the areas during inflammatory phase of MI (p=0.01). We noticed that numbers of CD68+, CD163+ and stabilin-1+ macrophages depended on MI phase. The number of CD68+ cells correlated with the day of MI: strong positive correlation was found in the infarct area (R=0.67, p=0.001) and moderate positive correlation was noticed in the peri-infarct area (R=0.55, p < 0.001). There was similar relationship for CD163+ (infarct area: R=0.61, p=0.001; peri-infarct area: R=0.66, p < 0.001) and stabilin-1+ cells (infarct area: R=0.6, p < 0.001; peri-infarct area: R=0.42, p=0.007). Conclusions: Our study translated experimental knowledge regarding macrophage subpopulations in post-infarction myocardial regeneration into clinical. We observed cardiac macrophage response following MI reminded a murine model. Our data indicate following: (1) dichotomous M1-M2 model is not sufficient to completely describe functions of macrophage subsets; (2) characterization of macrophage phenotypes by multiple biomarkers is promising; (3) stabilin-1 could be used as macrophage biomarker in cardiac wound healing in patients with MI. Our study supported diagnostic prospects for implementation of macrophage phenotyping in clinic. Identifying effective biomarkers of different macrophage subsets in patients with MI might become the basis of the method to predict adverse cardiac remodeling and the first step to develop myocardial regeneration target therapy

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

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