The body has the capacity to compensate for an occluded artery by creating a natural bypass upon increased fluid shear stress. How this mechanical force is translated into collateral artery growth (arteriogenesis) is unresolved. We show that extravasation of neutrophils mediated by the platelet receptor GPIbα and uPA results in Nox2-derived reactive oxygen radicals, which activate perivascular mast cells. These c-kit(+)/CXCR-4(+) cells stimulate arteriogenesis by recruiting additional neutrophils as well as growth-promoting monocytes and T cells. Additionally, mast cells may directly contribute to vascular remodeling and vascular cell proliferation through increased MMP activity and by supplying growth-promoting factors. Boosting mast cell recruitment and activation effectively promotes arteriogenesis, thereby protecting tissue from severe ischemic damage. We thus find that perivascular mast cells are central regulators of shear stress-induced arteriogenesis by orchestrating leukocyte function and growth factor/cytokine release, thus providing a therapeutic target for treatment of vascular occlusive diseases.

BackgroundChildhood obesity has increased dramatically and has become a public health concern worldwide. Childhood obesity is likely to persist through adulthood and may lead to early onset of NCDs. However, there is paucity of data on obesity among primary school children in Tanzania. This study assessed the prevalence and determinants of obesity among primary school children in Dar es Salaam.MethodsA cross sectional study was conducted among school age children in randomly selected schools in Dar es Salaam. Anthropometric and blood pressure measurements were taken using standard procedures. Body Mass Index (BMI) was calculated as weight in kilograms divided by the square of height in meters (kg/m2). Child obesity was defined as BMI at or above 95th percentile for age and sex. Socio-demographic characteristics of children were determined using a structured questionnaire. Logistic regression was used to determine association between independent variables with obesity among primary school children in Dar es Salaam.ResultsA total of 446 children were included in the analysis. The mean age of the participants was 11.1±2.0 years and 53.1% were girls. The mean BMI, SBP and DBP were 16.6±4.0 kg/m2, 103.9±10.3mmHg and 65.6±8.2mmHg respectively. The overall prevalence of child obesity was 5.2% and was higher among girls (6.3%) compared to boys (3.8%). Obese children had significantly higher mean values for age (p=0.042), systolic and diastolic blood pressures (all p<0.001). Most obese children were from households with fewer children (p=0.019) and residing in urban areas (p=0.002). Controlling for other variables, age above 10 years (AOR=3.3, 95% CI=1.5-7.2), female sex (AOR=2.6, 95% CI=1.4-4.9), urban residence (AOR=2.5, 95% CI=1.2-5.3) and having money to spend at school (AOR=2.6, 95% CI=1.4-4.8) were significantly associated with child obesity.ConclusionsThe prevalence of childhood obesity in this population was found to be low. However, children from urban schools and girls were proportionately more obese compared to their counterparts. Primary preventive measures for childhood obesity should start early in childhood and address socioeconomic factors of parents contributing to childhood obesity.

BackgroundWe assessed whether Angiopoietin-2 (Ang2), a Tie2 ligand and partial antagonist of Angiopoietin-1 (Ang1), is required for early vessel destabilization during postischemic angiogenesis, when combined with vascular growth factors.MethodsIn vitro, matrigel co-cultures assessed endothelial-cell tube formation and pericyte recruitment after stimulation of VEGF-A, Apelin (APLN), Ang1 with or without Ang2. In a murine hindlimb ischemia model, adeno-associated virus (rAAV, 3×1012 virusparticles) transduction of VEGF-A, APLN and Ang1 with or without Ang2 (continuous or early expression d0-3) was performed intramuscularly (d-14). Femoral artery ligation was performed at d0, followed by laser doppler perfusion meassurements (LDI) 7 and 14. At d7 (early timepoint) and d14 (late timepoint), histological analysis of capillary/muscle fiber ratio (CMF-R, PECAM-1) and pericyte/capillary ratio (PC-R, NG2) was performed.ResultsIn vitro, VEGF-A, APLN and Ang1 induced ring formation, but only APLN and Ang1 recruited pericytes. Ang2 did not affect tube formation by APLN, but reduced pericyte recruitment after APLN or Ang1 overexpression. In vivo, rAAV.VEGF-A did not alter LDI-perfusion at d14, consistent with an impaired PC-R despite a rise in CMF-R. rAAV.APLN improved perfusion at d14, with or without continuous Ang2, increasing CMF-R and PC-R. rAAV.Ang1 improved perfusion at d14, when combined with rAAV.Ang2 (d0-3), accompanied by an increased CMF-R and PC-R.ConclusionThe combination of early vessel destabilization (Ang2 d0-3) and continuous Ang1 overexpression improves hindlimb perfusion, pointing to the importance of early vessel destabilization and subsequent vessel maturation for enhanced therapeutic neovascularization.

BackgroundWhilst the burden of non-communicable diseases is increasing in developing countries, little data is available on blood pressure among Tanzanian children. This study aimed at determining the blood pressure profiles and risk factors associated with elevated blood pressure among primary school children in Dar es Salaam, Tanzania.MethodsWe conducted a cross sectional survey among 446 children aged 6–17 years from 9 randomly selected primary schools in Dar es Salaam. We measured blood pressure using a standardized digital blood pressure measuring machine (Omron Digital HEM-907, Tokyo, Japan). We used an average of the three blood pressure readings for analysis. Elevated blood pressure was defined as average systolic or diastolic blood pressure ≥ 90th percentile for age, gender and height.ResultsThe proportion of children with elevated blood pressure was 15.2% (pre-hypertension 4.4% and hypertension 10.8%). No significant gender differences were observed in the prevalence of elevated BP. Increasing age and overweight/obese children were significantly associated with elevated BP (p = 0.0029 and p < 0.0001) respectively. Similar associations were observed for age and overweight/obesity with hypertension. (p = 0.0506 and p < 0.0001) respectively. In multivariate analysis, age above 10 years (adjusted RR = 3.63, 95% CI = 1.03–7.82) was significantly and independently associated with elevated BP in this population of school age children.ConclusionsWe observed a higher proportion of elevated BP in this population of school age children. Older age and overweight/obesity were associated with elevated BP. Assessment of BP and BMI should be incorporated in school health program in Tanzania to identify those at risk so that appropriate interventions can be instituted before development of associated complications.

Objective— Although the investigation on the importance of mitochondria-derived reactive oxygen species (ROS) in endothelial function has been gaining momentum, little is known on the precise role of the individual components involved in the maintenance of a delicate ROS balance. Here we studied the impact of an ongoing dysregulated redox homeostasis by examining the effects of endothelial cell–specific deletion of murine thioredoxin reductase 2 (Txnrd2), a key enzyme of mitochondrial redox control. Approach and Results— We analyzed the impact of an inducible, endothelial cell–specific deletion of Txnrd2 on vascular remodeling in the adult mouse after femoral artery ligation. Laser Doppler analysis and histology revealed impaired angiogenesis and arteriogenesis. In addition, endothelial loss of Txnrd2 resulted in a prothrombotic, proinflammatory vascular phenotype, manifested as intravascular cellular deposits, as well as microthrombi. This phenotype was confirmed by an increased leukocyte response toward interleukin-1 in the mouse cremaster model. In vitro, we could confirm the attenuated angiogenesis measured in vivo, which was accompanied by increased ROS and an impaired mitochondrial membrane potential. Ex vivo analysis of femoral arteries revealed reduced flow-dependent vasodilation in endothelial cell Txnrd2-deficient mice. This endothelial dysfunction could be, at least partly, ascribed to inadequate nitric oxide signaling. Conclusions— We conclude that the maintenance of mitochondrial ROS via Txnrd2 in endothelial cells is necessary for an intact vascular homeostasis and remodeling and that Txnrd2 plays a vitally important role in balancing mitochondrial ROS production in the endothelium.

Objective— Arteriogenesis is strongly dependent on the recruitment of leukocytes, especially monocytes, into the perivascular space of growing collateral vessels. On the basis of previous findings that platelets are central players in inflammatory processes and mediate the recruitment of leukocytes, the aim of this study was to assess the role of platelets in a model of arterial remodeling. Approach and Results— C57Bl6 wild-type mice, IL4-R/Iba mice lacking the extracellular domain of the glycoprotein Ibα (GPIbα) receptor, and mice treated with antibodies to block GPIbα or deplete circulating platelets were studied in peripheral arteriogenesis. Using a novel model of intravital 2-photon and epifluorescence imaging, we visualized and quantified the interaction of platelets with leukocytes and the vascular endothelium in vivo. We found that transient platelet adhesion to the endothelium of collateral vessels was a major event during arteriogenesis and depended on GPIbα. Furthermore, leukocyte recruitment was obviously affected in animals with defective platelet GPIbα function. In IL4-R/Iba mice, transient and firm leukocyte adhesion to the endothelium of collateral vessels, as well as leukocyte accumulation in the perivascular space, were significantly reduced. Furthermore, we detected platelet–leukocyte aggregates within the circulation, which were significantly reduced in IL4-R/Iba animals. Finally, platelet depletion and loss of GPIbα function resulted in poor reperfusion recovery as determined by laser Doppler imaging. Conclusions— Thus, GPIbα-mediated interactions between platelets and endothelial cells, as well as leukocytes, support innate immune cell recruitment and promote arteriogenesis-establishing platelets as critical players in this process.

The increasing prevalence of overweight and obesity among children has become a public health concern both in developing and developed countries. Previous research studies have shown that favourable perception of one's body weight is an important factor in weight control. This study determined prevalence of overweight and obesity and assessed perception about body weight among primary schoolchildren in Dar es Salaam, Tanzania. In this cross sectional study, nine schools were selected randomly from a list of all primary schools in Dar es Salaam. A structured questionnaire was used to collect data on socio-demographic characteristics and lifestyle information including perception about body weight. Height and weight were measured following standard procedures. Chi-square tests and multiple logistic regressions were used to determine factors which influence perceptions about body weight. A total of 446 children were included into the study. The mean body mass index (BMI) was 16.6±4.0kg/m2 (16.1±4.0 for males and 17.0±4.0 for females). Prevalence of overweight and obesity was 9.8% and 5.2%, respectively. The prevalence of overweight and obesity was significantly higher among girls, 13.1% and 6.3% compared to boys with 6.3% and 3.8% overweight and obese respectively (P=0.0314). Overall, the prevalence of overweight and obesity was 15.0% (10.1% among boys and 19.4% among girls). One-third (33.3%) of the children perceived their body weight as overweight or obese. Among overweight and obese children, 35.4% had unfavourable perception of their body weights. There was a statistically significant difference between perceived body weight and actual body weight as indicated by BMI for both boys and girls (P<0.05). Age of the child (AOR=O.55 95%CI 0.36-0.85) and area of residence (COR=0.64 95% CI 0.44-0.95) were found to be significant predictors of favourable perception of one's body weight. In conclusion, the prevalence of overweight and obesity is not very high in this population. However over a third of overweight and obese children, had unfavourable perception of their body weights. We recommend targeted educational programmes about overweight and obesity and the associated health effects in order to instil a behaviour of self consciousness on overweight and obesity among children in Tanzania.

Background:Childhood obesity has increased over the past two decades. Child obesity is likely to persist through adulthood and increases the risk of non-communicable diseases (NCDs) later in life. This study assessed knowledge and attitudes towards obesity among primary school children in Dar es Salaam, Tanzania.Materials and Methods:A cross-sectional study was conducted in randomly selected primary schools in Dar es Salaam. A structured questionnaire was used to assess the knowledge and attitudes. Anthropometric and blood pressure measurements were taken using standard procedures.Results:A total of 446 children were included in the analysis. The mean age of the participants was 11.1 ± 2.0 years. The mean body mass index (BMI), systolic blood pressure (SBP) and diastolic blood pressure (DBP) were 16.6 ± 4.0 kg/m2, 103.9 ± 10.3 mmHg and 65.6 ± 8.2 mmHg, respectively. Prevalence of obesity (defined as BMI >95th percentile for age and sex) was 5.2%. Half of the children (51.1%) had heard about obesity from teachers at school (20%), radio (19.4%) and books/newspaper (17.3%). Less than half (45.4%) had knowledge about the risk factors for childhood obesity and correctly defined obesity (44.6%). However, a good number of the children (72.1%) were aware that they can be affected by obesity. Majority of them had negative attitude towards obesity and various factors leading to or resulting from childhood obesity.Conclusions:Knowledge about childhood obesity among primary school children is moderate and have negative attitude towards obesity. Integrating educational programs early in primary schools may be an effective strategy to impact knowledge about obesity and other non-communicable diseases early in childhood.