Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Stadler, J.
Investigating the Impact of Obesity and Gestational Hypertension on HDL Metabolism and Function in Women and their Offspring
PhD-Studium (Doctor of Philosophy); Humanmedizin; [ Dissertation ] Medizinische Universität Graz; 2023. pp. 210
[OPEN ACCESS]
FullText
- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Frank Sasa
- Marsche Gunther
- Wadsack Christian
- Altmetrics:
- Abstract:
- Obesity is a global health concern that is on the rise. It is strongly linked to an increased risk of numerous diseases, including cardiovascular disease and pregnancy-related disorders. The association between low levels of high-density lipoprotein (HDL)- cholesterol (HDL-C) and cardiovascular risk has long been established, but the protective functions of HDL extend far beyond just cholesterol content, as HDL particles are thought to exert protective effects against inflammation and cardiovascular disease. As part of my dissertation, I started with summarizing the existing literature on obesity-related changes in HDL metabolism and function and wrote a comprehensive review article. An intriguing finding is that bariatric surgery is highly effective in increasing HDL-C levels and improving HDL function in obese individuals. In the first research part of my thesis, I investigated whether obesity affects metabolism, composition and subclass distribution of HDL particles and analyzed them in a study cohort of young and healthy but overweight or obese women. Interestingly, the activities of enzymes such as lecithin-cholesterol acyltransferase and cholesteryl-ester transfer protein were profoundly increased in obese women, which was associated with a shift towards the small HDL subclasses. The composition of HDL particles was also altered, with enrichment in acute phase protein serum amyloid A and triglycerides, and lower content of cholesterol and apolipoprotein A-I. In the second part of my dissertation, I focused on obesity-related effects on HDL metabolism and function in mothers and their newborns. For this study, I used serum samples from the European study cohort DALI, which included overweight and obese pregnant women (BMI ≥ 29 kg/m2). In addition, cord blood samples were available and samples from a control group of pregnant women of normal weight were collected. In this study, we found that a high BMI caused changes in serum lipid profile and HDL metabolism and function in mothers, and also had effects on their offspring. Interestingly, HDL functionalities were strongly linked between mothers and children. Further, we showed that serum anti-oxidative capacity was reduced in obese mothers and their offspring. In addition, we investigated the changes in HDL function in gestational hypertension (GHTN), which is more prevalent in obese pregnant women in the DALI study cohort. GHTN significantly increases cardiovascular risk for mothers and their offspring later in life. Since HDL exhibits anti-atherogenic properties by promoting cholesterol uptake from macrophages and suppressing endothelial cell activation, a functional reduction in HDL functionalities could potentially contribute to the disease or long-term risk of cardiovascular events. While no changes in HDL function were observed in mothers with GHTN, impaired HDL-cholesterol efflux capacity and paraoxonase-1 activity in cord blood were observed in newborns, while serum antioxidant capacity was increased. Based on the observed changes in gestational hypertension (GHTN), the fourth part of my dissertation focused on studying lipid metabolism in pre-eclampsia (PE), a severe form of hypertension during pregnancy, and comparing it with pregnant women with normal blood pressure. PE was associated with atherogenic dyslipidaemia in the mothers, characterized by high triglyceride and low HDL-C levels. A shift from large to smaller HDL subclasses was observed in women with early-onset PE, which was related to increased plasma antioxidant capacity in mothers. PE was also associated with increased maternal HDL-associated apolipoprotein C-II levels. Total cholesterol levels were elevated in neonates with early-onset PE, while HDL cholesterol efflux capacity was reduced in neonates of late-onset PE group. Finally, as part of my dissertation, I conducted a comprehensive review on the current understanding of HDL metabolism, composition, and function of fetal HDL, with a p