Left ventricular hypertrophy (LVH) is more frequently associated with LV dilatation and systolic chamber dysfunction in males than in females. The mechanisms of this effect are uncertain. As excessive adrenergic stimulation may be responsible for LV dilatation and systolic chamber dysfunction in hypertension, in my dissertation I aimed to assess whether gender determines the adverse effects on LV chamber remodeling following 6 months of daily β-adrenergic receptor (AR) stimulation (isoproterenol [ISO] at 0.04 mg.kg-1day-1) in spontaneously hypertensive rats (SHR). LV dilatation was assessed in vivo from LV end diastolic diameter (EDD) (echocardiography) and ex vivo from the volume intercept at 0 mm Hg pressure (V0) of the LV diastolic pressure-volume relationship (isolated, perfused heart technique). LV systolic function was determined in vivo from LV endocardial fractional shortening (FSend) and ex vivo from the slope (LV end systolic elastance [LV Ees]) of the LV end systolic pressure-volume relationship (isolated, perfused heart technique). As compared to saline-treated male SHR (n=13), male SHR receiving ISO for 6 months (n=13) developed an increased LV EDD (Male Saline: 6.56±0.20 mm; Male ISO: 7.78±0.29 mm; p<0.05) and LV V0 (Male Saline: 0.22±0.01 ml; Male ISO: 0.31±0.02 ml; p<0.05). In contrast, ISO administration failed to modify LV EDD (Female Saline, n=13: 6.06±0.15 mm; Female ISO, n=12: 6.33±0.15 mm) or LV V0 (Female Saline: 0.17±0.01ml; Female ISO: 0.17±0.01 ml) in female SHR. In addition, there was a gender-ISO interactive effect on LV Ees (p<0.05; Male Saline: 2268±336 mmHg.ml-1; Male ISO: 1623±164 mmHg.ml-1; Female Saline: 1910±219 mmHg.ml-1; Female ISO: 2302±230 mmHg.ml-1). In conclusion, as compared to female SHR, male SHR are more susceptible to the adverse effects of chronic β-AR activation on LV cavity dimensions and systolic chamber function. These results suggest that the higher prevalence of LV dilatation and systolic chamber dysfunction in males than in females with LVH may be attributed to an increased susceptibility to the adverse effects of adrenergic stimulation.

M.Sc. (Med.), Faculty of Health Sciences, University of the Witwatersrand, 2009

Children with congenital heart defects and patients with faulty or failing valves have the need for a suitable aortic heart valve replacement. Current treatment options have several downfalls and heavy investigation is being done into the design of an engineered valve to find an alternative that would alleviate many of these issues. Understanding the physiology of how cells interact in vivo is crucial to the construction of such valve. This study investigates the effect of cyclic strain in aortic valve endothelial cells on the adhesion molecules, PECAM-1, ƒÒ1-Integrin, VE-Cadherin and Vinculin. Experiments found that cyclic strain plays a role in the development of cell/cell and cell/extracellular matrix adhesions and junctions and is extremely important in the pre-conditioning of a tissue engineered construct. Without this strain the new valve would be more susceptible to inflammation, injury or possible failure after being implanted into the patient.

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Racial disparities in maternal mortality in the United States are urgently in need of greater attention and research. The prevalence of preeclampsia is higher among African American women than White women by 1.7-fold, and African American women are three times more likely to die from preeclampsia complications. Among African American patients, Apolipoprotein L1 protein (APOL1) gene variants are known to be linked to increased risk for non-diabetic chronic kidney disease (CKD). The Sub-Saharan African population is particularly affected by these risk variants, and they also have one of the highest rates of preeclampsia in the world. Variants in the APOL1 gene are common, with about 40-50% of African American individuals carrying one variant, suggesting that APOL1 may underlie other health conditions that disproportionately affect patients of recent African origin, including preeclampsia. Previous epidemiologic studies support an association between APOL1 variants in the fetus and preeclampsia risk. There are also indications that in the kidney podocytes, these variants increase the endoplasmic reticulum (ER) specific stress protein GRP78, also known to regulate trophoblast syncytialization in the placenta. Although previous studies are suggestive, the mechanisms by which APOL1 variants alter placental function to increase preeclampsia risk are not understood. We utilized immunofluorescence (IF) studies to probe APOL1 expression in first trimester placenta (6-7 weeks gestation), as well as reverse-transcription polymerase chain reaction (RT-PCR) and Western blot studies to probe basal expression of messenger ribonucleic acid (mRNA) and protein of both APOL1 and GRP78 in BeWo cells. Our results have laid the foundation for studies of the role APOL1 plays in the genesis of preeclampsia. / 2026-03-06T00:00:00Z

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