Circulating Apoptotic Progenitor Cells in Patients with Congestive Heart Failure

Background: Circulating CD34+ endothelial progenitor cells (EPCs) are capable of differentiating into mature endothelial cells to assist in angiogenesis and vasculogenesis. We sought to quantify the numbers of apoptotic progenitors in patients with congestive heart failure. Methods and Results: Peripheral blood mononuclear cells were isolated by Ficoll density-gradient from 58 patients with various degrees of heart failure and 23 matched controls. Apoptosis in progenitor CD34+ cells was assessed using the Annexin V-PE/PI detection kit, and FACS analysis was performed with triple staining for CD34, annexin-V and propidium iodide. The percentage of early and late apoptotic progenitor cells was determined in the subject groups and was correlated with clinical characteristics. While there was no significant difference in total CD34 positive cells or early apoptotic progenitors between control subjects and CHF patients (p = 0.42) or between severe and mild/moderate CHF groups (p = 0.544), there was an elevated number of late apoptotic progenitors in the severe CHF group compared with the mild/moderate CHF group (p = 0.03). Late apoptotic progenitors were significantly increased in CHF patients as compared to matched controls. There was also an inverse correlation between late apoptotic progenitors and ejection fraction (r = 20.252, p = 0.028) as well as a positive association with NYHA class (r = 0.223, p = 0.046). Conclusion: Severe heart failure patients exhibited higher numbers of late apoptotic progenitors, and this was positivel

Experimental myocardial infarction induces altered regulatory T cell hemostasis, and adoptive transfer attenuates subsequent remodeling.

BACKGROUND: Ischemic cardiac damage is associated with upregulation of cardiac pro-inflammatory cytokines, as well as invasion of lymphocytes into the heart. Regulatory T cells (Tregs) are known to exert a suppressive effect on several immune cell types. We sought to determine whether the Treg pool is influenced by myocardial damage and whether Tregs transfer and deletion affect cardiac remodeling. METHODS AND RESULTS: The number and functional suppressive activity of Tregs were assayed in mice subjected to experimental myocardial infarction. The numbers of splenocyte-derived Tregs in the ischemic mice were significantly higher after the injury than in the controls, and their suppressive properties were significantly compromised. Compared with PBS, adoptive Treg transfer to mice with experimental infarction reduced infarct size and improved LV remodeling and functional performance by echocardiography. Treg deletion with blocking anti-CD25 antibodies did not influence infarct size or echocardiographic features of cardiac remodeling. CONCLUSION: Treg numbers are increased whereas their function is compromised in mice with that underwent experimental infarction. Transfer of exogeneous Tregs results in attenuation of myocardial remodeling whereas their ablation has no effect. Thus, Tregs may serve as interesting potential interventional targets for attenuating left ventricular remodeling

Correlations between early apoptotic/late apoptotic/total CD34+ EPCs and various parameters.

*<p>Statistically Significant.</p

Late apoptotic progenitor CD34+ cell percentage (out of total circulating progenitor CD34+ cells) in mild/moderate (NYHA class 1–3) and severe (NYHA class 4) CHF groups.

<p>Chi-square P value of the distribution of tertiles between NYHA 1–3 & NYHA = 4 is 0.038.</p

Baseline characteristics CHF and control patients.

*<p>LV ejection fraction was estimated by 2D echocardiography.</p>Δ<p>Ischemic cardiomyopathy refers to patients with ischemic heart disease (prior MI, PTCA or CABG) and ejection fraction <40%.</p

Associations between early apoptotic/late apoptotic/total CD34+ EPCs and various parameters.

*<p>Statistically Significant.</p

Representative flow cytometric dot plots: SSC/CD34 scatter (1a) and flow cytometric evaluation of progenitor CD34+ apoptotic cell percentage (1b).

<p>Dots in the lower right quadrant represent early apoptotic cells (Annexin-V positive and PI negative) while dots in the upper right quadrant represent late apoptotic cells (Annexin-V and PI positive).</p

Early apoptotic progenitor CD34+ cell percentage (out of total circulating progenitor CD34+ cells) in mild/moderate and severe CHF groups.

<p>P-value is >0.05 after adjustment for variables.</p