Abstract
BackgroundCirculating 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 ResultsPeripheral 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 = −0.252, p = 0.028) as well as a positive association with NYHA class (r = 0.223, p = 0.046).ConclusionSevere heart failure patients exhibited higher numbers of late apoptotic progenitors, and this was positively associated with NYHA class and negatively correlated with ejection fraction. This finding may shed light on the numerous factors governing the pathophysiology of CHF.
Highlights
Over the past few decades, researchers as well as clinicians have made great strides in understanding the pathophysiological mechanisms of heart failure
Severe heart failure patients exhibited higher numbers of late apoptotic progenitors, and this was positively associated with New York Heart Association (NYHA) class and negatively correlated with ejection fraction
circulating endothelial cells (CECs) are mature endothelial cells that have detached from the intimal monolayer of blood vessels in response to endothelial injury [6], whereas endothelial progenitor cells (EPCs) are immature, bone-marrow derived cells with the capacity to transform into mature endothelial cells and promote postnatal angiogenesis and vasculogenesis [7,8,9]
Summary
Over the past few decades, researchers as well as clinicians have made great strides in understanding the pathophysiological mechanisms of heart failure. Several diverse mechanisms contribute to this syndrome including structural and functional abnormalities of the heart, vascular disease, biological and neurohormonal factors, oxidative stress, genetics, environment and coexisting conditions [1]. While these advancements in understanding have led to better treatment of heart failure, it remains a major cause of morbidity and mortality worldwide. EPCs can be characterized by the expression of surface markers, such as CD34, CD133 and VEGFR-2 (KDR or Flk-1) in various combinations [10] It has, recently been shown by us that patients with heart failure have elevated circulating EPCs, which may be an independent predictor of mortality in CHF [11]. We sought to quantify the numbers of apoptotic progenitors in patients with congestive heart failure
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