Glucose challenge increases circulating progenitor cells in Asian Indian male subjects with normal glucose tolerance which is compromised in subjects with pre-diabetes: A pilot study

<p>Abstract</p> <p>Background</p> <p>Haematopoietic stem cells undergo mobilization from bone marrow to blood in response to physiological stimuli such as ischemia and tissue injury. The aim of study was to determine the kinetics of circulating CD34⁺and CD133⁺CD34⁺progenitor cells in response to 75 g glucose load in subjects with normal and impaired glucose metabolism.</p> <p>Methods</p> <p>Asian Indian male subjects (n = 50) with no prior history of glucose imbalance were subjected to 2 hour oral glucose tolerance test (OGTT). 24 subjects had normal glucose tolerance (NGT), 17 subjects had impaired glucose tolerance (IGT) and 9 had impaired fasting glucose (IFG). The IGT and IFG subjects were grouped together as pre-diabetes group (n = 26). Progenitor cell counts in peripheral circulation at fasting and 2 hour post glucose challenge were measured using direct two-color flow cytometry.</p> <p>Results</p> <p>The pre-diabetes group was more insulin resistant (p < 0.0001) as measured by homeostasis assessment model (HOMA-IR) compared to NGT group. A 2.5-fold increase in CD34⁺cells (p = 0.003) and CD133⁺CD34⁺(p = 0.019) cells was seen 2 hours post glucose challenge in the NGT group. This increase for both the cell types was attenuated in subjects with IGT. CD34⁺cell counts in response to glucose challenge inversely correlated with neutrophil counts (ρ = -0.330, p = 0.019), while post load counts of CD133⁺CD34⁺cells inversely correlated with serum creatinine (ρ = -0.312, p = 0.023).</p> <p>Conclusion</p> <p>There is a 2.5-fold increase in the circulating levels of haematopoietic stem cells in response to glucose challenge in healthy Asian Indian male subjects which is attenuated in subjects with pre-diabetes.</p

Nitric oxide synthetic pathway and cGMP levels are altered in red blood cells from end-stage renal disease patients

Red blood cells (RBCs) enzymatically produce nitric oxide (NO) by a functional RBC-nitric oxide synthase (RBC-NOS). NO is a vascular key regulatory molecule. In RBCs its generation is complex and influenced by several factors, including insulin, acetylcholine, and calcium. NO availability is reduced in end-stage renal disease (ESRD) and associated with endothelial dysfunction. We previously demonstrated that, through increased phosphatidylserine membrane exposure, ESRD-RBCs augmented their adhesion to human cultured endothelium, in which NO bioavailability decreased. Since RBC-NOS-dependent NO production in ESRD is unknown, this study aimed to investigate RBC-NOS levels/activation, NO production/bioavailability in RBCs from healthy control subjects (C, N = 18) and ESRD patients (N = 27). Although RBC-NOS expression was lower in ESRD-RBCs, NO, cyclic guanosine monophosphate (cGMP), RBC-NOS Serine1177 phosphorylation level and eNOS/Calmodulin (CaM)/Heat Shock Protein-90 (HSP90) interaction levels were higher in ESRD-RBCs, indicating increased enzyme activation. Conversely, following RBCs stimulation with insulin or ionomycin, NO and cGMP levels were significantly lower in ESRD- than in C-RBCs, suggesting that uremia might reduce the RBC-NOS response to further stimuli. Additionally, the activity of multidrug-resistance-associated protein-4 (MRP4; cGMP-membrane transporter) was significantly lower in ESRD-RBCs, suggesting a possible compromised efflux of cGMP across the ESRD-RBCs membrane. This study for the first time showed highest basal RBC-NOS activation in ESRD-RBCs, possibly to reduce the negative impact of decreased NOS expression. It is further conceivable that high NO production only partially affects cell function of ESRD-RBCs maybe because in vivo they are unable to respond to physiologic stimuli, such as calcium and/or insulin

Impaired endothelial progenitor cell function predicts age-dependent carotid intimal thickening

OBJECTIVES: We investigated whether qualitative or quantitative alterations of the endothelial progenitor cell (EPC) pool predict age-related structural vessel wall changes. BACKGROUND: We have previously shown that age-related endothelial dysfunction is accompanied by qualitative rather than quantitative changes of EPCs. Animal studies suggest that impaired EPC functions lead to accelerated arterial intimal thickening. METHODS: Intima-media thickness (IMT) was measured in the common carotid artery in our previously published groups of younger (25 +/- 1 years, n = 20) and older (61 +/- 2 years, n = 20) healthy non-smoking volunteers without arterial hypertension, hypercholesterolemia, and diabetes mellitus. Endothelial progenitor cells (EPCs, KDR(+)/CD34(+) and KDR(+)/CD133(+)) were counted in peripheral blood using flow cytometry. In ex vivo expanded EPCs, the function was determined as chemotaxis to VEGF, proliferation, and survival. RESULTS: We observed thicker IMT in older as compared to younger subjects (0.68 +/- 0.03 mm Vs. 0.48 +/- 0.02 mm, P < 0.001). Importantly, there were significant inverse univariate correlations between IMT, EPC chemotaxis, and survival (r = -0.466 P < 0.05; r = -0.463, P < 0.01). No correlation was observed with numbers of circulating EPCs. Multivariate regression analysis revealed that age, mean arterial pressure and migration of EPCs were independent predictors of IMT (R (2 )= 0.58). CONCLUSION: Impaired EPC function may lead to accelerated vascular remodeling due to chronic impairment of endothelial maintenance

Impaired Red Blood Cell Deformability in Patients with Coronary Artery Disease and Diabetes Mellitus

Patients with diabetes mellitus (DM) have an increased cardiovascular morbidity and mortality. There is increasing evidence that diabetes mellitus is associated with pathological hemorheological alterations, which might contribute to impaired coronary blood flow in coronary artery disease (CAD). We hypothesize that red blood cell (RBC) deformability is impaired in diabetic patients with CAD in comparison to nondiabetic patients with CAD. RBC deformability was measured in 21 patients with CAD and type 2 diabetes mellitus (CAD+DM) and 24 patients with CAD (CAD–DM). RBC deformability was measured by the Laser-assisted optical rotational cell analyzer by determining the elongation index (EI). RBC deformability was reduced in patients with CAD+DM in comparison to patients with CAD–DM (EI @ 1.12 Pa 0.236 ± 0.008 vs. 0.260 ± 0.005, p = 0.007). Inverse univariate correlations were found between the EI @ 1.12 Pa and plasma glucose concentration (r =-0.57; p<0.001) and HbA1c (r =-0.45; p = 0.002). Multivariate linear regression analysis identified plasma glucose concentration as the independent predictor of RBC deformability (β=-0.58; p = 0.007) thereby indicating that increased glucose concentrations determine RBC deformability in diabetic patients with CAD. In patients with CAD, diabetes mellitus leads to an impairment of RBC deformability which might contribute to increased morbidity of diabetic patients with CAD

Severe aortic valve stenosis in the elderly: high prevalence of sleep-related breathing disorders

Stefanie Keymel,1 Katharina Hellhammer,1 Tobias Zeus,1 Marc Merx,2 Malte Kelm,1 Stephan Steiner3 1Department of Cardiology, Pneumology, and Vascular Diseases, Medical Faculty, Heinrich Heine University D&uuml;sseldorf, D&uuml;sseldorf, 2Department of Cardiology, Vascular Diseases and Intensive Care Medicine, KRHKlinikum Robert Koch Gehrden, Gehrden, 3Department of Cardiology, Pneumology and Intensive Care Medicine, St Vincenz Hospital, Limburg, Germany Background: Aortic valve stenosis is common in the elderly, with a prevalence of nearly 3% in patients aged 75 years or older. Despite the fact that sleep-related breathing disorders (SRBD) are thought to be associated with cardiac disease, little is known about their prevalence in this patient cohort. The purpose of this study was to evaluate the prevalence of SRBD in older patients with aortic valve stenosis admitted for transcatheter aortic valve implantation.Methods: Forty-eight consecutive patients (mean age 81&plusmn;6 years; 37.5% male) with symptomatic aortic valve stenosis and considered for transcatheter aortic valve replacement were screened for SRBD. Sleep studies were performed by in-hospital unattended cardiorespiratory polygraphy measuring nasal air flow, chest and abdominal efforts, as well as oxygen saturation and body position. The patients were divided in subgroups dependent on the documented apnea&ndash;hypopnea index (AHI; no SRBD was defined as an AHI of &lt;5 events/hour; mild SRBD as AHI 5&ndash;15 events/hour, and moderate to severe SRBD as AHI &ge;15 events/hour).Results: Thirty-seven patients (77%) had SRBD defined as an AHI of &ge;5 events/hour. Eleven patients had an unremarkable investigation, with AHI &lt;5 events/hour (mean 3.0&plusmn;1.3 events/hour). Among patients with sleep apnea, 19 patients had mild SRBD, with an AHI of 5&ndash;15 events/hour (mean 9.9&plusmn;3.4 events/hour) and 18 patients had moderate to severe SRBD (mean 26.6&plusmn;11.3 events/hour). Mainly, obstructive apneas were found. Subgroups were not different regarding EuroSCORE (European System for Cardiac Operative Risk Evaluation) or aortic valve area. Also, no correlations were found between AHI and the additive or logistic EuroSCORE or aortic valve area. Significant correlations were found for AHI and N-terminal of the prohormone brain natriuretic peptide (r=0.53; P=0.003) and for AHI and glomerular filtration rate (r=-0.39; P=0.007). Conclusion: SRBD is common in elderly patients with symptomatic aortic valve stenosis admitted for transcatheter aortic valve replacement. Interestingly, this finding is not reflected by the currently used risk scores. Further randomized studies are needed to evaluate the clinical significance of concomitant SRBD in the management of severe aortic stenosis. Keywords: aortic valve stenosis, sleep-related breathing disorders, transcatheter aortic valve replacemen

Impaired Red Blood Cell Deformability in Patients with Coronary Artery Disease and Diabetes Mellitus

Patients with diabetes mellitus (DM) have an increased cardiovascular morbidity and mortality. There is increasing evidence that diabetes mellitus is associated with pathological hemorheological alterations, which might contribute to impaired coronary blood flow in coronary artery disease (CAD). We hypothesize that red blood cell (RBC) deformability is impaired in diabetic patients with CAD in comparison to nondiabetic patients with CAD. RBC deformability was measured in 21 patients with CAD and type 2 diabetes mellitus (CAD+DM) and 24 patients with CAD (CAD–DM). RBC deformability was measured by the Laser-assisted optical rotational cell analyzer by determining the elongation index (EI). RBC deformability was reduced in patients with CAD+DM in comparison to patients with CAD–DM (EI @ 1.12 Pa 0.236 ± 0.008 vs. 0.260 ± 0.005, p = 0.007). Inverse univariate correlations were found between the EI @ 1.12 Pa and plasma glucose concentration (r =-0.57; p<0.001) and HbA1c (r =-0.45; p = 0.002). Multivariate linear regression analysis identified plasma glucose concentration as the independent predictor of RBC deformability (β=-0.58; p = 0.007) thereby indicating that increased glucose concentrations determine RBC deformability in diabetic patients with CAD. In patients with CAD, diabetes mellitus leads to an impairment of RBC deformability which might contribute to increased morbidity of diabetic patients with CAD

Severe aortic valve stenosis in the elderly: high prevalence of sleep-related breathing disorders

Stefanie Keymel,1 Katharina Hellhammer,1 Tobias Zeus,1 Marc Merx,2 Malte Kelm,1 Stephan Steiner3 1Department of Cardiology, Pneumology, and Vascular Diseases, Medical Faculty, Heinrich Heine University D&uuml;sseldorf, D&uuml;sseldorf, 2Department of Cardiology, Vascular Diseases and Intensive Care Medicine, KRHKlinikum Robert Koch Gehrden, Gehrden, 3Department of Cardiology, Pneumology and Intensive Care Medicine, St Vincenz Hospital, Limburg, Germany Background: Aortic valve stenosis is common in the elderly, with a prevalence of nearly 3% in patients aged 75 years or older. Despite the fact that sleep-related breathing disorders (SRBD) are thought to be associated with cardiac disease, little is known about their prevalence in this patient cohort. The purpose of this study was to evaluate the prevalence of SRBD in older patients with aortic valve stenosis admitted for transcatheter aortic valve implantation.Methods: Forty-eight consecutive patients (mean age 81&plusmn;6 years; 37.5% male) with symptomatic aortic valve stenosis and considered for transcatheter aortic valve replacement were screened for SRBD. Sleep studies were performed by in-hospital unattended cardiorespiratory polygraphy measuring nasal air flow, chest and abdominal efforts, as well as oxygen saturation and body position. The patients were divided in subgroups dependent on the documented apnea&ndash;hypopnea index (AHI; no SRBD was defined as an AHI of &lt;5 events/hour; mild SRBD as AHI 5&ndash;15 events/hour, and moderate to severe SRBD as AHI &ge;15 events/hour).Results: Thirty-seven patients (77%) had SRBD defined as an AHI of &ge;5 events/hour. Eleven patients had an unremarkable investigation, with AHI &lt;5 events/hour (mean 3.0&plusmn;1.3 events/hour). Among patients with sleep apnea, 19 patients had mild SRBD, with an AHI of 5&ndash;15 events/hour (mean 9.9&plusmn;3.4 events/hour) and 18 patients had moderate to severe SRBD (mean 26.6&plusmn;11.3 events/hour). Mainly, obstructive apneas were found. Subgroups were not different regarding EuroSCORE (European System for Cardiac Operative Risk Evaluation) or aortic valve area. Also, no correlations were found between AHI and the additive or logistic EuroSCORE or aortic valve area. Significant correlations were found for AHI and N-terminal of the prohormone brain natriuretic peptide (r=0.53; P=0.003) and for AHI and glomerular filtration rate (r=-0.39; P=0.007). Conclusion: SRBD is common in elderly patients with symptomatic aortic valve stenosis admitted for transcatheter aortic valve replacement. Interestingly, this finding is not reflected by the currently used risk scores. Further randomized studies are needed to evaluate the clinical significance of concomitant SRBD in the management of severe aortic stenosis. Keywords: aortic valve stenosis, sleep-related breathing disorders, transcatheter aortic valve replacemen