IFN-I Mediates Dysfunction of Endothelial Progenitor Cells in Atherosclerosis of Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a multi-system autoimmune disease including the cardiovascular system. Atherosclerosis is the most common cardiovascular complication of SLE and a significant risk factor for morbidity and mortality. Vascular damage/protection mechanism in SLE patients is out of balance, caused by the cascade reaction among oxidative stress, proinflammatory cytokines, Neutrophil Extracellular Traps, activation of B cells and autoantibodies and abnormal T cells. As a precursor cell repairing vascular endothelium, endothelial progenitor cells (EPCs) belong to the protective mechanism and show the reduced number and impaired function in SLE. However, the pathological mechanism of EPCs dysfunction in SLE remains ill-defined. This paper reviews the latest SLE epidemiology and pathogenesis, discusses the changes in the number and function of EPCs in SLE, expounds the role of EPCs in SLE atherosclerosis, and provides new guidance and theoretical basis for exploring novel targets for SLE treatment.

Endothelial Progenitor Cells in Heart Failure: an Authentic Expectation for Potential Future Use and a Lack of Universal Definition.

Congestive heart failure (CHF) is a prevalent disease (especially among the elderly) with high mortality and morbidity rates. The pathological hallmark of CHF is a loss of cardiomyocytes leading to cardiac fibrosis and dysfunctional cardiac remodeling, which culminates in organ failure. Endothelial progenitor cells (EPCs) are bone marrow-derived cells that contribute to maintenance of the integrity of endothelial wall and protect ischemic myocardium through forming new blood vessels (vasculogenesis) or proliferation of pre-existing vasculature (angiogenesis). Despite its potential, little is known about EPCs and their function in CHF. Here, we define EPC and its role in health and CHF, highlighting their contributions as a cornerstone in the maintenance of a healthy endothelium. Thereafter, we explore the behavior and relevance of EPCs in the pathophysiology of CHF, their prognostic importance, and possible utilization of EPCs as therapy for CHF. Lastly, the restrictions surrounding the use of EPCs in clinical practice will be discussed.

Endothelial progenitor cells and vascular endothelial growth factor in patients with Takayasu's arteritis.

BACKGROUND: Endothelial progenitor cells (EPCs) are responsible for endothelial damage repair. Takayasu's arteritis (TA) is a chronic inflammatory disease that affects large vessels. The aim of the study was to evaluate the number of EPCs and the levels of vascular endothelial growth factor (VEGF) and the relationship of these variables in patients with TA. METHODS: Thirty women with TA and 30 healthy controls were included. EPCs were assessed by flow cytometry and cell culture and VEGF quantification was performed by commercial ELISA kits. RESULTS: Ages of patients and controls were similar. The number of EPCs in patients and controls (median (interquartile range) were 0.0073% (0.0081%) vs. 0.0062% (0.0089%), p = 0.779 by flow cytometry and 27.0 (42.3) colony forming units (CFUs) vs. 27.0 (20.5) CFUs, p = 0.473 by cells culture, respectively. VEGF levels in patients and controls was 274.5 (395.5) pg/ml vs. 243.5 (255.3) pg/ml, p = 0.460. There was no difference in the number of EPCs and VEGF level between patients with active and inactive disease. There was a tendency of the number of angioblast-like EPCs in patients taking anti-TNFs to be higher; and in patients using methotrexate to be lower. CONCLUSION: No significant difference was found in the quantification of EPCs and VEGF levels in TA patients compared to controls, and no difference was observed between patients with active and inactive disease.

Concise Review: Functional Definition of Endothelial Progenitor Cells: A Molecular Perspective.

: Since the discovery of endothelial progenitor cells (EPCs) almost 2 decades ago, there has been great hope in their use in treating chronic ischemic disease. Unfortunately, to date, many of the clinical trials using EPCs have been hampered by the lack of clear definition of this cell population. Attributes of a progenitor population are self-renewal and multipotentiality. Major progress has been achieved moving from a definition of EPCs based on a candidate cell surface molecule to a functional definition based essentially on self-renewal hierarchy of endothelial colony-forming cells (ECFCs). More recent work has seized on this functional characterization to associate gene expression signatures with the self-renewal capacity of ECFCs. In particular, Notch signaling driving the quiescence of progenitors has been shown to be central to progenitor self-renewal. This new molecular definition has tremendous translational consequences, because progenitors have been shown to display greater vasculogenic potential. Also, this molecular definition of EPC self-renewal allows assessment of the quality of presumed EPC preparations. This promises to be the initial stage in progressing EPCs further into mainstream clinical use. SIGNIFICANCE: The development of a therapy using endothelial progenitor cells provides great hope for patients in treating cardiovascular diseases going forward. For continual development of this therapy toward the clinical, further understanding of the fundamental biology of these cells is required. This will enable a greater understanding of their stemness capacity and provide insight into their ability to differentiate and drive tissue regeneration when injected into a host.

Relation between endothelial progenitor cells and arterial stiffness in patients with psoriasis.

Patients with psoriasis are prone to premature atherosclerosis. We hypothesize that depletion of circulating endothelial progenitor cells (EPC) is related to patients with psoriasis and can contribute to the development of atherosclerosis. Thirty-five plaque-type psoriasis patients (41.9 ± 5.5 years, 30 men) and 20 age- and sex-matched controls were studied. Four subpopulations of EPC, namely, CD34(+) EPC, CD133(+) EPC, CD34(+) /kinase insert domain-containing receptor (KDR)(+) EPC and CD133(+) /KDR(+) EPC were measured by flow cytometry. Arterial stiffness in psoriasis patients was assessed by heart to ankle pulse wave velocity (haPWV), augmentation index (AI) and carotid intima media thickness (IMT). Patients with psoriasis had a lower level of CD34(+) EPC (7.85 ± 2.49% vs 6.26 ± 2.13%, P = 0.02) compared with healthy controls. In patients with psoriasis, level of CD34(+) EPC was negatively related with haPWV (r = -0.43 P = 0.01) and Psoriasis Area and Severity Index (r = -0.39 P = 0.02). Multivariate regression analysis further demonstrated that haPWV was independently associated with level of CD34(+) EPC. Each percentage decrease in CD34(+) EPC accounted for an increase in haPWV of +0.02 m/s. The result demonstrated that patients with psoriasis had reduced CD34(+) EPC compared with controls. Importantly, CD34(+) EPC was independently related with haPWV in these patients. This finding suggests that EPC reduction is associated with the development of arterial stiffness in patients with psoriasis.

Changes in endothelial progenitor cell subsets in normal pregnancy compared with preeclampsia.

BACKGROUND: The results of studies measuring the number of endothelial progenitor cells (EPCs) in normal pregnancies and in preeclampsia have been highly controversial or even contradictory because of cross-sectional designs and different methodologies enumerating three distinct subsets of EPCs: circulating angiogenic cells (CAC), colony-forming unit endothelial cell (CFU-ECs), and endothelial colony forming cells (ECFCs). To provide a clear explanation for these underlying controversies, we designed a prospective study to compare the number of all EPC subsets between three trimesters of normal gestation and a case-control study to compare these values as preeclampsia occurs with those from gestational age (GA) matched normal pregnancy. METHODS: Samples from peripheral blood of nine women were taken during their three consecutive trimesters of normal pregnancy, and from eight women with preeclampsia. To cover most of the reported phenotypes for CACs and ECFCs in the literature, we enumerated 13 cell populations by quantitative flow cytometry using various combinations of the markers CD34, CD133, CD309, and CD45. We used routine culturing techniques to enumerate CFU-ECs. RESULTS: The numbers of CACs and ECFCs were higher in women with preeclampsia (p = 0.014). By contrast, preeclampsia was associated with a reduced number of CFU-ECs (p = 0.039). The CAC number rose with the increase in GA (p = 0.016) during normal pregnancy, while the number of CFU-ECs and ECFCs did not differ during the trimesters. CONCLUSION: Although we did demonstrate an increase in absolute counts of CACs and ECFCs in preeclampsia, fewer colony formation capacities indicated a loss in their functional capabilities. By contrast, the number of CACs increased without alterations in colony formation ability in normal pregnancy with the growth of the fetus. Here, by comparing different methodologies to calculate the number of EPC subsets, we could imitate the existing controversy in the literature for such calculations, which may help to elucidate clearer explanations.