Proefschrift Universiteit Maastricht. / Met lit. opg. - Met samenvatting in het Nederlands.

Proefschrift Maastricht. / Met lit. opg. - Met samenvatting in het Nederlands.

Proefschrift Maastricht. / Lit. opg.: p. 117-127. - Met samenvatting in het Nederlands.

Proefschrift Universiteit Maastricht. / Met lit. opg. - Met een samenvatting in het Nederlands.

Proefschrift Maastricht. / Met lit. opg. - Met samenvatting in het Nederlands.

Proefschrift Maastricht. / Lit. opg. - Met samenvatting in het Nederlands.

Proefschrift Universiteit Maastricht. / Met lit. opg. - Met een samenvatting in het Nederlands.

Proefschrift Universiteit Maastricht. / Met lit. opg. - Met samenvatting in het Nederlands.

Thesis (doctoral)--University of Utrecht, 1983. / Summary in English and Dutch. Includes bibliographical references.

Motivation - Brain-derived neurotrophic factor (BDNF) is a protein complex, synthesised and secreted mainly by the central nervous system and is involved in neuronal maintenance. Research suggests that BDNF is implicated in various neurological and psychiatric diseases, while recent evidence suggests a role for the neurotrophin on the periphery as well. Indeed, the specific functional role of BDNF and its action mechanism in the cardiovascular system, especially in that of Africans, is yet to be determined. The cardiovascular health profile of black South Africans is a major concern as research has shown that this group suffers from an array of cardiovascular risk factors that may result in organ damage. Sub-clinical atherosclerosis or structural endothelial dysfunction contributes to ever-increasing morbidity and mortality in the world. However, no studies regarding the associations between BDNF and structural vascular disease have been undertaken relating to black African participants. Objectives - The objective of this study was to determine whether BDNF is associated with changes in ambulatory blood pressure (BP) and whether a relationship between BDNF and structural endothelial dysfunction exists in black African male and female participants, determined by cross sectional wall area (CSWA) and albumin:creatinine ratio (ACR). Methodology - The study included 172 black African teachers (82 males and 90 females) who were employed by the Kenneth Kaunda Education district of the North-West Province, South Africa. Ambulatory blood pressure recordings were obtained with the use of a Meditech CE120 CardioTens ® apparatus. Blood pressure readings were measured at 30 min intervals during the day and 60 min intervals during the night. Anthropometric measurements were performed in triplicate by registered level II anthropometrists according to standardised procedures. A high-resolution ultrasound scan with carotid intima-media thickness (CIMT) images from at least two optimal angles of the left and right common carotid artery were obtained using a SonoSite Micromaxx ultrasound system. The lumen diameter between the near and far wall of the lumen-intima interface and the averages of both the left and right common carotid arteries were calculated. Subsequently, the carotid cross-sectional wall area (CSWA) was calculated. Participants, who fasted overnight, provided eight-hour blood and urine samples to determine serum BDNF and metabolic markers, for example, hyperglycaemia (HbA1c) and gamma glutamyl transferase (GGT). Urinary albumin and creatinine levels were determined by means of a turbidimetric method with the use of a Unicel DXC 800 analyser from Beckman and Coulter (Germany) and expressed as a ratio between albumin and creatinine (ACR). BDNF median split x Gender interaction effects for structural ED justified stratification of BDNF into low and high (≤ / > 1.37 ng/ml) gender groups. Results and Conclusion - On average, male participants were overweight (BMI 25-30kg/m2) and abused more alcohol.21 African men revealed a vulnerable cardiometabolic profile with values exceeding cut–points (European Society of Hypertension). These men demonstrated increased acute and chronic glucose (HbA1c) levels indicating a pre-diabetic state; as well as a disturbed lipid profile with lower HdL and increased triglycerides. Overall BDNF levels were lower than reference ranges (6.97 – 42.6 ng/ml). The men revealed mean lower BDNF levels, ambulatory BP values exceeding guideline cut-points (ambulatory SBP > 130mmHg; DBP > 80mmHg) as well as a hypertensive state compared to their female counterparts. Pertaining to structural endothelial dysfunction, the mean ACR value in men exceeded normal laboratory values (< 3.5mg/mmol). The African women displayed an obese state with low grade inflammation (CRP, 12.27 ± 11.67mg/l). A single two-way ANCOVA interaction on main effects (BDNF median split x Gender) demonstrated significant interaction for CIMTf [F (1,164); 3.99, p=0.05] and cholesterol [F (1,164); 4.12, p=0.05]. Therefore, a median split approach was followed which stratified gender groups into lower (≤ 1.37 ng/ml) and higher BDNF levels (>1.37 ng/ml). The low BDNF men revealed higher cholesterol than the high BDNF group, independent of BMI and age. Only the low BDNF women indicated significantly higher values for structural vascular markers (p< 0.05) than the high BDNF female group. In conclusion, we accept our hypothesis, as hypertrophic remodelling of the carotid artery was associated with lower BDNF levels. This may imply attenuated or possibly down-regulated BDNF levels acting as a compensatory mechanism for the mean higher BP levels. In women, metabolic risk and hypertrophic remodelling were evident within higher circulating levels of BDNF, underpinning different underlying mechanisms for impaired neurotrophin health in men and women. Novel findings of BDNF revealed the impact of central neural regulation on the circulatory system, which may contribute to cardiometabolic risk in Africans. / MSc (Physiology), North-West University, Potchefstroom Campus, 2014