Objective-Increased risk of cardiovascular disease in patients with chronic renal failure (CRF) has been explained by accelerated atherosclerosis and impaired angiogenesis, in which endothelial progenitor cells (EPCs) may play key roles. We hypothesized that altered EPC biology may contribute to the pathophysiology of CRF. Methods and Results-EPCs were isolated from CRF patients on maintenance hemodialysis (nϭ44) and from a normal control group (nϭ30). CRF patients showed markedly decreased numbers of EPC (44.6%) and colonies (75.3%) when compared with the controls (PϽ0.001). These findings were corroborated by 30.5% decrease in EPC migratory function in response to vascular endothelial growth factor (VEGF) (Pϭ0. T he lifespan of patients with chronic renal failure (CRF) is reduced, and coronary artery disease is the most important cause of morbidity and mortality in these patients. 1,2 Even the results of therapeutic strategies such as percutaneous coronary intervention and bypass surgery have shown poor procedural success rates and dismal long-term eventfree survival in CRF patients. 3,4 Most of the increased cardiovascular morbidity and mortality in CRF has been accounted for by the rapid progression of atherosclerosis, which is clinically shown to be accelerated in CRF. 5,6 Experimental studies have also shown that even mild renal dysfunction causes a dramatic acceleration of atherosclerosis. 7 Angiogenesis, which is an essential compensation for myocardial ischemia, is also impaired in CRF. 8 However the mechanism underlying the acceleration of atherosclerosis and impaired angiogenesis by CRF has not been examined closely. Although the phenomenon has been partially explained by the higher prevalence of established risk factors in CRF, such as hypertension, abnormal carbohydrate metabolism, and increased low density lipoprotein (LDL) cholesterol, the extent and severity of cardiovascular disease is clearly disproportionately high relative to the underlying risk factor profile. 9,10 Recent studies have identified that normal adults have a small amount of circulating endothelial progenitor cell (EPC) in the peripheral blood. In response to cytokine stimulation and ischemic insult, these cells are mobilized from bone marrow, home to the ischemic tissue, and contribute to neovascularization and angiogenesis. 11-14 Moreover, EPC is regarded to have a key role in the maintenance of vascular integrity and to act as "repair" cells in response to the endothelial injury, 15,16 which has been regarded as an initial step in atherosclerosis and a result of the actions of various cardiovascular risk factors. 17 Current data suggest that decrease in circulating EPC contributes not only to impaired angiogenesis but also to the progression of atherosclerosis, 18 and patients at risk for coronary artery disease have a decreased number of circulating EPC with impaired activity. 19 -22 Therefore, we reasoned that EPC, which is critical for neovascularization and the maintenance of vascular integrity, Methods Study SubjectsWe...

Extracorporeal cardiopulmonary resuscitation showed a survival benefit over conventional cardiopulmonary resuscitation in patients who received cardiopulmonary resuscitation for >10 mins after witnessed inhospital arrest, especially in cases with cardiac origins.

Endothelial progenitor cells (EPCs) act as endothelial precursors that promote new blood vessel formation and increase angiogenesis by secreting growth factors and cytokines in ischemic tissues. These facts prompt the hypothesis that EPC transplantation should accelerate the wound-repair process by facilitating neovascularization and the production of various molecules related to wound healing. In a murine dermal excisional wound model, EPC transplantation accelerated wound re-epithelialization compared with the transplantation of mature endothelial cells (ECs) in control mice. When the wounds were analyzed immunohistochemically, the EPCtransplanted group exhibited significantly more monocytes/ macrophages in the wound at day 5 after injury than did the EC-transplanted group. This observation is consistent with enzyme-linked immunosorbent assay results showing that EPCs produced in abundance several chemoattractants of monocytes and macrophages that are known to play a pivotal role in the early phase of wound healing. At day 14 after injury, the EPC-transplanted group showed a statistically significant increase in vascular density in the granulation tissue relative to that of the EC-transplanted group. Fluorescence microscopy revealed that EPCs preferentially moved into the wound and were directly incorporated into newly formed capillaries in the granulation tissue. These results suggest that EPC transplantation will be useful in dermal wound repair and skin regeneration, because EPCs both promote the recruitment of monocytes/macrophages into the wound and increase neovascularization. Stem Cells 2005;23:1571-1578

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Plasma level of NT-proBNP is the most powerful prognostic factor in both HFpEF and HFrEF. Although patients with HFpEF have lower NT-proBNP levels, the prognosis of a patient with HFpEF expected from a given NT-proBNP level is similar with his/her counterpart with HFrEF.

Objective:To investigate whether simple and non-invasive measurement of N-terminal pro-brain natriuretic peptide (NT-proBNP) and/or C-reactive protein (CRP) can predict perioperative major cardiovascular event (PMCE).Design:Prospective, single-centre, cohort study.Setting:A 1900-bed tertiary-care university hospital in Seoul, KoreaDesign and patients:The predictive power of NT-proBNP, CRP and Revised Cardiac Risk Index (RCRI) for the risk of PMCE (myocardial infarction, pulmonary oedema or cardiovascular death) were evaluated from a prospective cohort of 2054 elective major non-cardiac surgery patients. Optimal cut-off values were derived from receiver operating characteristic curve (ROC) analysis.Main outcome measurement:PMCE (myocardial infarction, pulmonary oedema or cardiovascular death) within postoperative 30 days.Results:PMCE developed in a total of 290 patients (14.1%). Each increasing quartile of NT-proBNP or CRP level was associated with a greater risk of PMCE after adjustment for traditional clinical risk factors. The relative risk (RR) of highest versus lowest quartile was 5.2 for NT-proBNP (p<0.001) and 3.7 for CRP (p<0.001). Both NT-proBNP (cut-off  = 301 ng/l) and CRP (cut-off  = 3.4 mg/l) predicted PMCE better than RCRI (cut-off  = 2) by ROC analysis (p<0.001). Moreover, the predictive power of RCRI (adjusted RR  = 1.5) could be improved significantly by addition of CRP and NT-proBNP to RCRI (adjusted RR 4.6) (p<0.001).Conclusions:High preoperative NT-proBNP or CRP is a strong and independent predictor of perioperative major cardiovascular event in non-cardiac surgery. The predictive power of current clinical risk evaluation system would be strengthened by these biomarkers.

Coxsackievirus B3 (CVB3) infections induce myocarditis in humans and mice. Little is known about the molecular characteristics of CVB3 that activate the cellular immunity responsible for cardiac inflammation. Previous experiments have identified an antibody escape mutant (H310A1) of a myocarditic variant of CVB3 (H3) that attenuates the myocarditic potential of the virus in mice in spite of ongoing viral replication in the heart. We have cloned full-length infectious cDNA copies of the viral genome of both the wild-type myocarditic H3 variant of CVB3 and the antibody escape mutant H310A1. Progeny viruses maintained the myocarditic and attenuated myocarditic potential of the parent viruses, H3 and H310A1. The full sequence of the H3 viral cDNA is reported and compared with those of previously published CVB3 variants. Comparison of the full sequences of H3 and H310A1 viruses identified a single nonconserved mutation (A to G) in the P1 polyprotein region at nucleotide 1442 resulting in an asparagine-to-aspartate mutation in amino acid 165 of VP2. This mutation is in a region that corresponds to the puff region of VP2. Nucleotide 1442 of the H3 and H310A1 cDNA copies of the viral genome was mutated to change amino acid 165 of VP2 to aspartate and asparagine, respectively. The presence of asparagine at amino acid 165 of VP2 is associated with the myocarditic phenotype, while an aspartate at the same site reduces the myocarditic potential of the virus. In addition, high-level production of tumor necrosis factor alpha by infected BALB/c monocytes is associated with asparagine at amino acid 165 of VP2 as has been previously demonstrated for the H3 virus. These findings identify potentially important differences between the H3 variant of CVB3 and other previously published CVB3 variants. In addition, the data demonstrate that a point mutation in the puff region of VP2 can markedly alter the ability of CVB3 to induce myocarditis in mice and tumor necrosis factor alpha secretion from infected BALB/c monocytes.

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