Oxidative stress and angiogenesis in Africans and Caucasians: the SAfrEIC study

Thesis (MSc (Physiology))--North-West University, Potchefstroom Campus, 2013.Motivation and aim - The prevalence of hypertension is higher in Africans compared to Caucasians. African Americans also show higher levels of oxidative stress. However, literature regarding levels of oxidative stress and the angiogenic growth factors, vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang-2), are limited in black South Africans. There is also a dearth of literature regarding the relationship between oxidative stress and angiogenesis in hypertensive individuals. Therefore, the aim of this study was to investigate whether a relationship exist between the two angiogenic growth factors and oxidative stress and to determine their relationship with cardiovascular measurements. Methods - This study was a sub-study of the cross-sectional SAfrEIC study (South African study on the influence of Sex, Age and Ethnicity on Insulin sensitivity and Cardiovascular function) and originally included 750 African and Caucasian men and women aged 20 to 70 years. Only 626 participants’ information was used after excluding pregnant or lactating women, as well as those infected with the human immunodeficiency virus. The participants were from semi-urban areas in the North West Province of South Africa Anthropometric measurements of each participant were taken in triplicate following standard procedures. Systolic and diastolic blood pressure and heart rate were measured after a 10-minute rest in a sitting position, using the OMRON HEM-757 device. Two measurements were taken with a 5-minute rest interval. Cardiovascular measurements were performed using the FinometerTM device. Fasting blood glucose was directly measured in the Metabolic Unit by a nurse using an enzymatic method to screen for diabetes mellitus. A fasting blood sample was taken from the antebrachial vein using a sterile winged infusion set and syringes. Standard methods were used to prepare plasma and serum samples, which were stored at -80ºC until analyses. Serum reactive oxygen species (ROS) were determined with a high-throughput spectrophotometric assay, with 1 unit equaling 1 mg/liter H2O2. Human VEGF165 and human Ang-2 were determined with enzyme-linked immunosorbant assays (ELISA). Results - When viewing the characteristics of the African and Caucasian groups, the Africans showed higher blood pressures (p<0.001) as well as significantly higher levels of ROS (p=0.002), VEGF (p=0.002) and Ang-2 (p<0.001). They also included more smokers (p<0.001) and hypertensive individuals (p<0.001). The use of anti-hypertensive medication was significantly higher in the Caucasian group (p<0.001). In single regression analyses, there were no significant correlations between VEGF or Ang-2 and blood pressure in the African and Caucasian groups. ROS correlated significantly with the two angiogenic growth factors in both groups of men, being stronger in the African men (both r=0.33; p<0.001) but less so in the Caucasian men (r=0.16; p=0.04 and r=0.16; p=0.07). ROS was also significantly correlated with Ang-2 in the African women (r=0.26; p=0.003). In addition to this, ROS associated significantly, but weakly with diastolic blood pressure in the Caucasian women (r=0.15; p=0.03). We plotted VEGF and Ang-2 by quartiles of ROS and adjusted for age and body mass index. In all instances, African men and women showed significant associations of VEGF and Ang-2 with ROS (p for trend < 0.05), except for the association between VEGF and ROS in African women (p for trend=0.80). Conversely, no significant associations were indicated for the Caucasian gender groups. To further investigate the significant associations found only in the African group, we performed multiple regression analyses with blood pressure or markers of angiogenesis as dependent variables. After full adjustment for confounders, the associations of both the angiogenic growth factors with ROS in the African men (both p=0.014) and Ang-2 with ROS in the African women (p=0.025) were confirmed. No associations were found between the angiogenic growth factors or ROS with blood pressure. Conclusion - We found in our study, involving angiogenic growth factors and oxidative stress, that Ang-2 was significantly associated with oxidative stress in African men and women. Additionally, VEGF was linked to oxidative stress only in African men. These associations were absent in both the Caucasian gender groups. The strong association found in the African population possibly add to the existing high risk of cardiovascular disease in this population.Master