Regulatory T cell frequency and function in acute myocardial infarction patients and its correlation with ventricular dysfunction.

A high percentage of patients with acute coronary syndrome develop heart failure due to the ischemic event. Regulatory T (Treg) cells are lymphocytes with suppressive capacity that control the immune response and include the conventional CD4+ CD25hi Foxp3+ cells and the CD4+ CD25var CD69+ LAP+ Foxp3- IL-10+ cells. No human follow-up studies focus on Treg cells' behavior after infarction and their possible relationship with ventricular function as a sign of post-ischemic cardiac remodeling. This study aimed to analyze, by flow cytometry, the circulating levels of CD69+ regulatory T cells and CD4+ CD25hi Foxp3+ cells, its IL-10+ production as well as their function in patients with acute myocardial infarction (AMI), and its possible relation with ventricular dysfunction. We found a significant difference in the percentage of CD4+ CD25hi Foxp3+ cells and IL-10+ MFI in patients with AMI at 72 hours compared with the healthy control group, and the levels of these cells were reduced six months post-AMI. Regarding the suppressive function of CD4+ CD25+ regulatory cells, they were dysfunctional at three- and six-months post-AMI. The frequency of CD69+ Treg cells was similar between patients with AMI at 72 hours post-infarction and the control groups. Moreover, the frequency of CD69+ Treg cells at three months and six months post-ischemic event did not vary over time. Treg cells play a role in regulating inflammation after an acute myocardial infarction, and its function may be compromised in this pathology. This work is the first report to evaluate CD69+ Foxp3- Treg cells in AMI patients.

Altered NK cell receptor repertoire and function of natural killer cells in patients with acute myocardial infarction: A three-month follow-up study.

NK cells are important in the onset of acute myocardial infarction (AMI) by their ability to secrete IFN-γ and other inflammatory cytokines. They also participate in regulating pathological cardiac remodeling after myocardial infarction. Mechanisms of regulation, however, are incompletely understood. Herein, the aim of this study is to explore the possible association between the expression pattern of different NK cell receptors (phenotype), as well as the cytotoxic function of NK cells from AMI patients with their myocardial function after three months follow-up. We analyzed the phenotype and function of both CD56dimCD16+ and CD56brightCD16- NK cells from twenty-one patients within the first 72 h after ST-elevation AMI and three-month follow-up, as well as fifteen healthy controls. Clinical characteristics and ventricular function determined by echocardiography were also evaluated. NK cells from AMI patients showed an activated phenotype, characterized by high TNF-α production and low percentages of the activating receptor NKG2D. Interestingly, AMI patients display higher levels of circulating IL-10+ NK cells. Three-month follow-up showed that NK cells exhibit a diminished cytotoxic function. These data show that NK cells may have a role mediating myocardial remodeling by regulating the inflammatory response, mainly by the production of IL-10. We also propose that NKG2D may have a role in the onset of the inflammatory response immediately after AMI. The precise regulation of NK cells function may represent an important step in recovery of myocardial function.

[Cell therapy for ischemic heart disease]. / La terapia celular en la cardiopatía isquémica.

Ischemic heart disease is the leading cause of death and heart failure worldwide. That is why it is important to develop new therapeutic modalities to decrease mortality and long-term complications in these patients. One of the main lines of research worldwide is myocardial regeneration, using progenitor cells in order to improve systolic and diastolic function in patients with ischemic heart disease, as well as to increase their survival. There have been carried out, with great enthusiasm worldwide, human and animal studies to define the usefulness of stem cells in the management of patients with ischemic heart disease. Today, regenerative therapy in ischemic heart disease is considered a novel therapeutic tool, with substantial theoretical benefits and few side effects. Here we present the scientific principles that support the use of this therapy, discuss the current clinical evidence available; and point out the controversial issues still not clarified on its use and usefulness in the short and long term.

La terapia celular en la cardiopatía isquémica / Cell therapy for ischemic heart disease

La cardiopatía isquémica es la principal causa de muerte e insuficiencia cardiaca a nivel mundial. Esto hace de vital importancia el desarrollo de nuevas modalidades terapéuticas, que disminuyan la mortalidad y complicaciones a largo plazo en estos pacientes. Una de las principales líneas de investigación a nivel mundial es la regeneración miocárdica a partir de células progenitoras, con el fin de mejorar la función sistólica y diastólica de los pacientes con cardiopatía isquémica, además de incrementar su sobrevida. Con bases teóricas y fisiológicas sobre la función de estas células, se han llevado a cabo con gran entusiasmo a nivel mundial, estudios en animales y humanos para tratar de definir la utilidad del empleo de las células madre, en el manejo de los pacientes con cardiopatía isquémica. En la actualidad, la terapia regenerativa en la cardiopatía isquémica es considerada una herramienta terapéutica novedosa, de beneficios teóricos considerables y pocos efectos adversos. En esta revisión presentamos los fundamentos científicos básicos que apoyan el empleo de esta terapia, la evidencia clínica actual sobre su beneficio. Señalamos los puntos controversiales y las perspectivas sobre su empleo y utilidad a corto y largo plazo.

Ischemic heart disease is the leading cause of death and heart failure worldwide. That is why it is important to develop new therapeutic modalities to decrease mortality and long-term complications in these patients. One of the main lines of research worldwide is myocardial regeneration, using progenitor cells in order to improve systolic and diastolic function in patients with ischemic heart disease, as well as to increase their survival. There have been carried out, with great enthusiasm worldwide, human and animal studies to define the usefulness of stem cells in the management of patients with ischemic heart disease. Today, regenerative therapy in ischemic heart disease is considered a novel therapeutic tool, with substantial theoretical benefits and few side effects. Here we present the scientific principles that support the use of this therapy, discuss the current clinical evidence available; and point out the controversial issues still not clarified on its use and usefulness in the short and long term.