Saudi Cultural Missions Theses & Dissertations
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Item Restricted Hypertensive Kidney Disease and The Role of Toll-Like Receptor 4(Saudi Digital Library, 2026) Almarshood, Hebah; Sen, UtpalIntroduction: Hypertension is one of the leading causes of kidney disease. Persistently high, uncontrolled blood pressure (BP) can constrict the blood vessels within the kidneys, impairing their ability to regulate fluids and eliminate waste. This deterioration of renal function can result in serious health complications. Moreover, hypertension can initiate a self-perpetuating cycle of innate immune activation, which contributes to structural changes and worsens kidney dysfunction. Research from our laboratory and others has identified toll-like receptors (TLRs) as key mediators in this immune response associated with hypertensive kidney injury. Of the thirteen known TLRs in mammals, TLR4 plays a particularly significant role: its activation during hypertension triggers a range of cellular responses, some of which are pathological and contribute to kidney damage. Conversely, studies have shown that genetic mutation (beneficial) or pharmacological inhibition of TLR4 can limit organ injury, including kidney damage, in hypertensive models. Despite these findings, the precise mechanisms by which TLR4 contributes to hypertensive kidney damage and dysfunction remain unclear. Objectives: The main objective of this dissertation was to investigate whether hypertension, via the stress response, activates TLR4, subsequently triggering inflammatory pathways, tissue remodeling, and kidney dysfunction. A further objective was to determine if mutation or inhibition of TLR4 can mitigate pathological kidney remodeling and dysfunction associated with hypertension. Methods: In vivo experiments were conducted using both female and male C3H/HeOuJ and C3H/HeJ mice, aged 10–12 weeks. The C3H/HeOuJ mice possess normal TLR4 function (designated TLR4N in this study), whereas C3H/HeJ mice carry a spontaneous mutation in the TLR4 gene (designated TLR4M). Hypertension and related pathologies were induced in these mice by infusing them with angiotensin II (Ang-II, 1000 ng/kg/min) using Alzet mini-osmotic pumps for four weeks. Physiological and pathological parameters, including systolic and mean arterial pressure (MAP) and kidney function as indicated by glomerular filtration rate (GFR), were monitored throughout and at the conclusion of the 4-week period. At the end of the experiments, kidneys were collected for biochemical, histological, protein, and mRNA analyses. For the in vitro model, mouse kidney mesangial cells were cultured in a humidified incubator at 37°C with 5% CO2 until they reached 60% to 70% confluence, displaying a uniform density. Cells were seeded in DMEM/F-12 (50/50) medium supplemented with 5% fetal bovine serum, antibiotics, and L-glutamine. In a 6-well plate, the cells were pre-treated with 200 nM TAK-242 (a TLR4 inhibitor) for one hour, followed by exposure to 200 nM Angiotensin-II for 24 hours. Subsequently, the cells were collected for further laboratory analysis. Appropriate controls were used in all experiments. Results: Results showed that Ang II significantly elevated blood pressure in TLR4N mice, whereas TLR4M mice were resistant to this increase under the same Ang II treatment. In TLR4N mice, hypertension also led to a significant upregulation of TLR4 expression in the kidney, increased levels and activity of matrix metalloproteinases (MMPs), and reduced levels of their natural inhibitors, tissue inhibitors of matrix metalloproteinases (TIMPs). Similar results were observed in in vitro experiments with mesangial cells. Additionally, TLR4N hypertensive mice exhibited elevated inflammatory markers, increased apoptosis, and pyroptosis in the kidneys, all of which were mediated by activation of the NF-κB signaling pathway. Moreover, TLR4N mice displayed increased collagen genes expression, glomerular hypercellularity, reduced renal blood flow, higher resistive index, and impaired renal function following Ang II-induced hypertension. Notably, all these adverse changes were mitigated in TLR4M mice subjected to the same hypertensive regimen. Summary and Conclusion: Hypertension activates the TLR4 receptor, triggering a cascade of immune responses that disrupts the balance of MMPs and TIMPs in the renal vasculature. This activation also drives pyroptosis and apoptosis via the NF-kB signaling pathway, ultimately leading to impaired kidney function. Conversely, TLR4 mutation or inhibition offers targeted strategies to mitigate vascular damage and enhance renal function in hypertension. Together, these findings indicate that hypertension promotes kidney remodeling and dysfunction through TLR4 activation, while TLR4 mutation (TLR4M) or inhibition confers protection against renal remodeling and improves kidney function in hypertensive conditions. Further research is required to validate these model-based findings in preclinical and clinical studies.20 0Item Restricted Designing Health Education Program about the Nutritional Needs of Hypertensive Patients(Saudi Digital Library, 2025) Alkulayb, Mohammed; Awad, Lamiaa AminThis study aimed to was to design a health education program about the nutritional needs of hypertensive patients.A study was conducted at healthcare centers primary Khabash governorate, Najran region, Saudi Arabia. Delphi technique was used. A judgmental sample of 20 experts engaged in multiple Delphi rounds to develop the program’s components. Also, the program was assessed by 10 health educators (users) and 16 hypertensive patients ( end beneficiaries) selected using purposive sampling across six PHC centers. Data were gathered using five tools as semi-structured interviews, Delphi surveys, and structured feedback tools. Quantitative data were analyzed using SPSS version 20; qualitative data underwent thematic analysis.5 0Item Restricted EARLY SCREENING USING ECHOCARDIOGRAPHY TO ASSESS LEFT VENTRICULAR REMODELING IN HYPERTENSIVE PATIENTS AT HAIL CARDIAC CENTRE, SAUDI ARABIA(Saudi Digital Library, 2025-08) Alsrur, Hamad Hamoud H; Zarihah, binti Mohd ZainBackground: Hypertension is a major global public health issue and a leading risk factor for cardiovascular morbidity and mortality. Early detection of left ventricular (LV) remodeling is essential to prevent progression to heart failure. Echocardiography, including advanced techniques such as Global Longitudinal Strain (GLS), provides detailed insights into subclinical myocardial dysfunction that may not be detected by conventional parameters. Objectives: This study aimed to assess early markers of LV remodeling among hypertensive patients at Hail Cardiac Centre, Saudi Arabia, and to evaluate the role of GLS compared with conventional measures such as left ventricular ejection fraction (LVEF) and left ventricular mass index (LVMI). Methods: A cross-sectional study was conducted on 341 hypertensive adult patients (aged 18–69 years) attending Hail Cardiac Centre between 2023 and 2024. Demographic, clinical, and echocardiographic data were collected, including LVEF, LVMI, relative wall thickness (RWT), and GLS using speckle-tracking echocardiography. Descriptive and comparative statistical analyses were performed to evaluate the association between hypertension-related variables and LV remodeling indices. Results: The mean age of patients was 53.2 ± 10.8 years, with a nearly equal distribution of males and females. LVEF values were within the normal range in most patients; however, GLS revealed subclinical dysfunction in some cases despite preserved LVEF, demonstrating its sensitivity for early detection of hypertensive-related changes. A considerable proportion of patients also exhibited increased LVMI and RWT, reflecting structural remodeling. GLS showed stronger associations with clinical variables compared to LVEF, underscoring its diagnostic significance. Conclusion: Echocardiographic evaluation of hypertensive patients demonstrates that conventional measures such as LVEF may appear normal, whereas GLS can uncover subtle dysfunction at an earlier stage. Incorporating GLS alongside LVMI in routine echocardiographic screening may improve early detection of LV remodeling and support timely clinical interventions in hypertensive patients. Remodeling, Subclinical Dysfunction.23 0Item Unknown EFFECT OF HYPERTENSION CONTROL ON ALZHEIMER’S DISEASE AND RELATED DEMENTIAS(University of Florida, 2025) Jafari, Eissa; Caitrin, McDonoughAlzheimer’s Disease and Related Dementias (ADRD) represent a critical public health challenge, exacerbated by an aging population and rising healthcare demands. Yet, recent data remain limited regarding ADRD prevalence trends overall and by subtypes, as well as ADRD characteristics in high-risk populations, including African Americans, Hispanics, individuals with hypertension (HTN), and those experiencing social disadvantages. Furthermore, although HTN is widely recognized as a modifiable risk factor for ADRD, there is a lack of evidence on the differential impacts of HTN control levels, particularly apparent treatment-resistant hypertension (aTRH), on ADRD development and associated cardiovascular outcomes. This dissertation addresses these gaps through three interconnected aims using electronic health record data from the OneFlorida Data Trust (2012–2022). Aim 1 characterized ADRD prevalence trends overall and by subtypes, and identified characteristics in high-risk populations. Among 106,874 ADRD patients, ADRD prevalence increased over the last decade, with variability observed across subtypes. Unspecified dementia was the predominant subtype (72%). HTN, diabetes, stroke, high social deprivation, female sex, and peripheral artery disease emerged as prominent ADRD characteristics in high-risk groups. Aim 2 evaluated the effect of different HTN control levels on cardiovascular outcomes in 9,430 ADRD patients. Compared to ADRD patients without HTN, those with uncontrolled HTN showed the highest cardiovascular risk (HR: 1.97, 95% CI: 1.54–2.51), followed by patients with well-controlled HTN (HR: 1.53, 95% CI: 1.22–1.93), intermediate-controlled HTN (HR: 1.49, 95% CI: 1.16–1.90), and aTRH (HR: 1.30, 95% CI: 1.04–1.63). Aim 3 assessed how HTN control levels and social deprivation influence ADRD development within a cohort of 57,273 HTN patients. Compared to well-controlled HTN, aTRH significantly increased ADRD risk (HR: 1.16, 95% CI: 1.09–1.24). Additionally, higher levels of social deprivation were associated with increased ADRD risk. In conclusion, this dissertation offers key insights by characterizing ADRD and its subtypes, analyzing prevalence trends, and identifying patient characteristics in high-risk populations. Our findings highlight the importance of effective blood pressure control in reducing cardiovascular events among ADRD patients and lowering the risk of ADRD development. Additionally, they highlight socioeconomic status as a critical factor influencing ADRD risk and informing prevention strategies.19 0Item Restricted EFFECTIVENESS OF PILATES EXERCISES VERSUS DIAPHRAGMATIC BREATHING IN PATIENTS WITH HYPERTENSION(Saudi Digital Library, 2025) AL SHARIF, NAWAF; ABDEL GHAFFAR, HEBAPurpose of the study: The aim of this study was to investigate the effect of Pilates exercises versus diaphragmatic breathing exercises on blood pressure and fasting lipid profile in patients with hypertension. Methods: Sixty male patients with hypertension (class I & class II) were recruited for this study from Physiotherapy department at King Khalid hospital in Najran city, The kingdom of Saudi Arabia. Their ages ranged from 45 to 60 years. Patients were assigned into three equal groups: group A (Pilates exercises group), group B (Diaphragmatic breathing exercises group), and group C (Control group). Patients received the prescribed interventions 3 times per week for 8 weeks. The outcome measures were Systolic blood pressure, Diastolic blood pressure, and Fasting lipid profile (Total cholesterol, LDL cholesterol, HDL cholesterol, and Triglycerides). The assessment was made before and after the study. Results: The results revealed that Systolic blood pressure, Diastolic blood pressure, Total cholesterol, LDL cholesterol, HDL cholesterol, and Triglycerides were significantly improved in all groups compared to baseline (P<0.05). Group A (Pilates group) showed more significant improvement in all outcome measures than group B (Diaphragmatic breathing group) and group C (Control group) (P<0.05). Conclusion: it could be concluded that both Pilates exercises and diaphragmatic breathing exercises may have significant effects on blood pressure and fasting lipid profile in patients with hypertension. However, Pilates exercises may be more effective than diaphragmatic breathing exercises in improving these outcomes.10 0Item Restricted The impact of Dairy- free diet on the management of Hypertension- A systematic review.(University of Nottingham, 2024) Alzubidi, Fatimah; McCullough, FionaIntroduction: Hypertension is a significant risk factor for chronic diseases, and its prevalence is increasing globally. The development of hypertension is influenced by genetic predisposition, environmental factors, age-related changes, and immunological influences. Dietary management plays a key role in managing hypertension, with the DASH diet being an effective intervention. Calcium intake through diet, particularly from dairy products, has been shown to help lower blood pressure. Previous studies have demonstrated a link between dairy consumption and decreased blood pressure. Aim: This paper aimed to systematically review the existing literature by comparing diets without dairy to those that include dairy, focusing on the effect of dairy exclusion on hypertension, which was the primary outcome, as well as on secondary outcomes, such as changes in lipid profile, weight, waist circumference, and glucose levels. Methods: PubMed, Scopus, Embase, and Web of Science were used to search for relevant articles that study the impact of dairy food exclusion on the management of hypertension. Only records that met the following inclusion criteria were considered: published between 2000 and June 2024, full text, and in English, focusing on adults aged ≥18 years of either gender, with or without health conditions. The Cochrane Collaboration quality assessment tool was employed to assess the included studies. Results: The results of six randomised clinical trials involving 462 adult participants indicated that a dairy-free diet did not have any discernible effect on both systolic and diastolic blood pressure measurements (in mmHg). Conclusion: This review indicates that eliminating dairy products from one's diet has no apparent impact on the incidence or management of hypertension despite the limitations of the included studies. Moreover, it emphasises the need for additional research to explore the effects of fat content and micronutrients on the management of hypertension.31 0Item Restricted INVESTIGATING CHANGES IN ANGIOTENSIN II SIGNALLING, RESPIRATORY VARIABILITY AND CAROTID BODY FUNCTION IN RESPONSE TO CHRONIC HYPOXIA(University of Birmingham, 2024-08-05) Aldossary, Hayyaf Saad; Holmes, Andrew; Coney, AndrewChronic hypoxia (CH) and rises in circulating angiotensin II (Ang II) are key features of chronic obstructive pulmonary disease (COPD), an illness associated with respiratory dysfunction. Hypertension is an important co-morbidity in COPD. It has recently been suggested that the carotid body (CB) has an important role in causing vascular dysfunction in COPD patients. In response to CH, the CB undergoes extensive structural and functional adaptation, leading to hyperactivity. It is proposed that CB hyperactivity contributes to hypertension development in CH/COPD. The CB serves as a peripheral chemoreceptor located at the common carotid artery bifurcation, sensing and reacting to alterations in arterial O2, CO2, and pH levels. Previous studies have suggested the involvement of Ang II and its G Protein-Coupled Receptor (GPCR) member, AT1R, in mediating CB activity. It is currently unknown if the membrane arrangement of AT1Rs is altered by CH. It is not clear if Ang II stimulation involves activation of TRPC channels. Furthermore, a role for heightened Ang II-AT1R-TRPC signalling in mediating CB hyperactivity in response to CH remains uncertain. Key aims of this thesis were to: 1. Assess if AT1R membrane protein expression is increased in CH, 2. Explore how single molecule organisation of AT1R is modified by CH, 3. Provide a detailed evaluation of respiratory changes induced by CH, 4. Identify if CB Ang II-TRPC signalling is upregulated in CH and 5. Determine if targeting Ang II-TRPC signalling in vivo decreases the blood pressure in CH animals. In Chapter 2 and 3, utilizing the PC12 cell line as a surrogate for CB type I cells, it was revealed that AT1R protein expression was elevated by CH, accompanied by modifications in cell size, suggesting adaptive responses to prolonged hypoxia. Subsequent investigations utilising super-resolution microscopy demonstrated that AT1Rs form distinct clusters in the cell membrane. Furthermore, the maximum cluster size is increased under CH, indicating enhanced supercluster formation. In Chapter 4, expanding beyond cellular responses, the impact of CH on respiratory variables was evaluated using whole body plethysmography. It revealed key alterations, such as rises in respiratory frequency, shortening of respiratory timings and elevations in inspiratory and expiratory drive. Furthermore, a decrease in breath to breath interval variability was observed after CH exposure. In Chapter 5, carotid sinus nerve (CSN) activity measurements showed augmented, more consistent responses to Ang II that were apparent in a greater proportion of fibres in the CH group, suggesting increased Ang II sensitivity. In the presence of Ang II, the TRPC channel blocker, specifically 2-APB, produced exaggerated inhibition of CB activity in the CH group, suggestive of a rise in Ang II-TRPC signalling. Lastly, in Chapter 6, cardiovascular measurements showed that single bolus injection of 2-APB did not successfully decrease the mean arterial pressure (MAP) or heart rate (HR) in CH animals. This is likely due to it not reaching a high enough concentration in the CB. These investigations provide comprehensive information regarding AT1R, CB and respiratory adaptations to CH. The findings should help guide the development of novel therapeutic interventions, based on targeting Ang II-AT1R-TRPC signalling, to treat CB hyperactivity in conditions such as COPD.13 0Item Restricted Socioeconomic inequalities in cardiovascular diseases risk factors: Analysis of the Health Survey of England(Saudi Digital Library, 2023-11-01) Abideen, Raseel; Douiri, AbdelIntroduction: Cardiovascular diseases present a significant global health challenge, contributing substantially to morbidity and mortality. This complex issue arises from a confluence of genetic, lifestyle, and environmental factors. Despite medical advancements, socioeconomic determinants persist as formidable barriers to achieving equitable health outcomes. Addressing these inequalities is pivotal in mitigating the impact of cardiovascular diseases on public health. Aim: The primary aim of this research is to investigate the association between socioeconomic factors and the prevalence of three cardiovascular risk factors: hypertension, obesity, and smoking. By delving into the Health Survey of England dataset for 2019, this study seeks to unravel the complex web of associations that link demographic and socioeconomic strata with the prevalence of these risk factors. Methodology: This research adopts a cross-sectional design, leveraging the comprehensive Health Survey of England dataset. Analyzing a range of demographic and socioeconomic variables, the study employs rigorous statistical methods, including chi-square tests, logistic regression, and descriptive analysis. This approach offers a comprehensive examination of the relationships between socioeconomic factors and cardiovascular risk profiles. Results: The study offers nuanced insights into the interplay of age and hypertension, revealing a significant surge in prevalence and odds beyond the age of 45. Distinct ethnic disparities in hypertension prevalence highlights higher rates among Black individuals, signifying their increased susceptibility. Socioeconomic status emerges as an important factor, with lower income groups displaying elevated odds of hypertension. Exploring obesity patterns uncovers the influence of gender and culture, with males at higher risk and Asian ethnic groups displaying lower odds. Socioeconomic status is again noteworthy, as higher standing correlates with decreased obesity risk. Smoking behaviors exhibit age-related variation, with young adults aged 25-34 displaying the highest prevalence and likelihood of being current smokers. Ethnic disparities in smoking behaviors underscore cultural influences, while income and deprivation complexities link with smoking behaviors. Conclusion: This dissertation underscores the interconnected nature of age, gender, ethnicity and socioeconomic status in shaping cardiovascular risk profiles. Recommendations include targeted interventions for hypertension among older adults and ethnic minority populations, culturally sensitive obesity interventions, and comprehensive antismoking initiatives. Findings emphasize the significance of addressing health disparities and fostering equitable health outcomes in the pursuit of a healthier future for all.28 0Item Restricted EFFICACY OF ANTIDIABETIC DRUGS IN NORMALIZING BLOOD PRESSURE IN HYPERTENSIVE DIABETIC ANIMALS AND NOVEL MECHANISMS IN THE DISTAL NEPHRON(Saudi Digital Library, 2023) Gholam, Mohammed Fawzi A; Alli, AbdelHypertension associated diabetes is a highly prevalent disease and a major risk factor for DN, the most common cause of end stage renal disease in the US. The regulation of salt balance by the kidney is a major player for blood pressure regulation by adjusting blood volume in response to changes in systemic pressure. NCC and ENaC are expressed mainly in the late DCT and play a crucial role in blood pressure regulation. The cytoskeleton of eukaryotic cells provides structural support for the plasma membrane and regulates numerous epithelial transport proteins. Multiple antidiabetic drugs including, dapagliflozin and metformin, have shown a positive effect on the kidney. However, less is known about their mechanisms of action in terms of blood pressure regulation. The goals of this project are to define the mechanistic link between NCC and ENaC and the actin cytoskeleton proteins in the diabetic hypertensive db/db mice, furthermore, to investigate the effects of the antidiabetic agents including dapagliflozin and metformin on sodium reabsorption and blood pressure. We found that NCC interacts with the actin cytoskeleton filamin A and is dependent on CaMKII activity, which may serve as a feedback mechanism to maintain basal levels of NCC activity in the distal nephron. Moreover, we identified a novel blood pressure reducing role of metformin in diabetic nephropathy by regulating the cathepsin B-ENaC axis. Besides, we found the augmentation of cathepsin isoforms in the diabetic db/db mouse kidney is associated with an increase in renal MARCKS expression and proteolysis. On the other hand, NCC and the actin cytoskeleton linker protein ezrin interacts at the DCT in the hypertensive diabetic kidney. Dapagliflozin reduced NCC and ezrin interaction and alleviated blood pressure, blood glucose, urine osmolality, and promoted urinary sodium. Furthermore, some bioactive lipids in diabetic kidney membranes were altered after dapagliflozin treatment. Taken together, metformin and dapagliflozin may have the potential to normalize blood pressure in diabetics and reduce the risk of developing diabetic nephropathy.31 0Item Restricted Do Respiratory Influences on Cardiovascular Regulation Provide Early Markers of Hypertension in Young Adults with Family History of Hypertension?(2023-05-05) Al Enazi, Fahad; Marshall, Janice; Coney, AndrewBackground: Hypertension is well-known leading cause of the majority of cardiovascular diseases. Individuals with a parental history of hypertension (FH+) have a two-fold greater risk of developing hypertension than those without parental hypertension (FH-). Objective: This PhD project had three main aims. First, to elucidate whether young normotensive adult FH+ already have disturbed autonomic regulation of arterial blood pressure (ABP) relative to FH- at rest and in response to everyday stressors such as postural manoeuvres and environmental stressors. Second, to investigate whether slow breathing normalises autonomic dysregulation in FH+. Third, to assess whether slow breathing acutely or following training reduces ABP and restores autonomic regulation in normotensives and hypertensives. Methods: The first and second aims were explored by recording arterial blood pressure (ABP), a range of haemodynamic variables, heart rate variability (HRV) and baroreceptor reflex sensitivity (BRS), in young normotensive FH+ and FH- men and women at rest, during and following acute mental stress (Stroop colour-word test) and during acute slow breathing at 6 breaths/minute. The third aim was evaluated by a systematic review and meta-analysis on the effects of device- and non-device guided slow breathing acutely and by training for ≥4 weeks on ABP and autonomic regulation of ABP in normotensives and hypertensives. Results and Conclusion: The experimental studies showed no differences between FH+ and FH- at rest. However, FH+ showed exaggerated increases in ABP and total peripheral resistance to mental stress relative to FH-. On the other hand, HRV, which mainly reflects vagal influences on the heart, was reduced during mental stress in FH+ and FH- and consistent with inhibition of the baroreceptor reflex being a characteristic of the defence response, vagal BRS was also reduced in FH+ and FH-. However, sympathetic BRS to a fall in ABP assessed by the squat to stand test was depressed by mental stress in FH- but not FH+. These findings provide novel evidence that sympathetic control of ABP is disturbed in young adult FH+ such that repeated exposure to mental stressors would be expected to increase their risk of hypertension. Acute slow breathing reduced ABP in both FH+ and FH- but reduced TPR in FH- only. Concomitantly, HRV was increased in both groups, while vagal BRS was increased in FH+ only. Theses novel results suggest that FH+ are more resistant to the ability of slow breathing to reduce sympathetic tone, but that vagal influence are normalised. Importantly, the systematic review and meta-analysis, demonstrated that slow breathing is effective in both hypertensives and normotensives in lowering ABP, enhancing HRV, and improving BRS, at least in normotensives. Thus, collectively the results indicate that slow breathing training should help to reduce abnormal autonomic regulation in young FH+ by increasing vagal regulation of the heart and decreasing sympathetic activity to the heart and vasculature, so lowering their future risk of hypertension.30 0