Abstract:
Hypertensive disorders and proteinuria are heightened in obese pregnancies, attributed partly to hyperleptinemia. Leptin, associated with obesity, correlates positively with body fat and is elevated in hypertensive pregnant women. Endothelial dysfunction, linked to obesity and hypertensive disorders of pregnancy, implicates inflammatory mediators. Leptin administration induces proteinuria and hypertension during pregnancy, possibly via endothelial activation pathways. ACE2, a counter-regulator to ACE, shows promise in cardiovascular diseases. Its expression increases in normal pregnancy, yet its role in pathological pregnancies remains uncertain. We hypothesized that leptin-induced hypertension involves altered ACE2 activity and expression.
This study investigates the effect of ACE2 activation on leptin-induced changes in systolic blood pressure(SBP), proteinuria, endothelial activation and ACE2 expression during pregnancy in Sprague-Dawley rats. Pregnant rats were given subcutaneous injections of either saline, or leptin, or leptin plus xanthenone(ACE2 activator), or xanthenone (XTN) alone. SBP, serum ACE, ACE2, endothelin-1, E-selectin and ICAM-1 levels were estimated; their gene expressions were also determined in the kidney and aorta, respectively. Compared to the control, SBP was higher in the leptin-only treated group (P < 0.001) and lower in rats treated with xanthenone alone (P < 0.01). Proteinuria and markers of endothelial activation were significantly higher than controls in leptin-only treated rats (P < 0.05). ACE2 activity and expression were lower in leptin-only treated rats when compared to controls (P < 0.05).
In summary, leptin administration during pregnancy-induced hypertension and proteinuria, accompanied by alterations in serum biomarkers and gene expressions associated with endothelial activation. Co-administration of XTN mitigated these effects, suggesting a potential therapeutic role for ACE2 activation in pregnancy-related complications. Further investigations are warranted to elucidate these findings' underlying mechanisms and clinical implications.
What will the audience learn from the presentation?
- Insights into the Link Between Obesity and Pregnancy Complications: Attendees will gain a deeper understanding of how obesity, through factors like leptin, contributes to hypertension and proteinuria during pregnancy. This knowledge can inform future research and clinical practice in both obesity management and obstetrics.
- Novel Therapeutic Approach: By introducing ACE2 activation by xanthenone as a potential therapeutic intervention for mitigating pregnancy-related complications induced by leptin, the presentation offers a new avenue for managing obesity-related hypertension and proteinuria during pregnancy.
- Clinical Applications for Healthcare Professionals: Healthcare professionals specializing in obesity management, obstetrics, and related fields can apply the findings from this presentation to optimize patient care. Understanding the molecular mechanisms underlying pregnancy-related complications enables more targeted and effective treatment strategies.
- Interdisciplinary Collaboration: This research bridges the gap between obesity research and obstetrics, demonstrating the interconnectedness of various physiological pathways. It encourages interdisciplinary collaboration among researchers, clinicians, and professionals working in diverse fields to address complex health issues.
- Educational Resource: Faculty members can utilize this research to enhance teaching materials on obesity-related pregnancy complications and the molecular mechanisms involved. It provides valuable content for academic courses, seminars, and workshops focused on obesity, pregnancy, and women's health.
- Innovative Design Solutions: Designers and developers of pharmacological interventions or therapeutic approaches can leverage the insights gained from this research to create more targeted and efficient treatments for pregnancy-related hypertension and proteinuria. This may lead to the development of novel drugs or therapies with improved efficacy and safety profiles.
- Advancement of Scientific Knowledge: By presenting cutting-edge research on the role of ACE2 activation in pregnancy complications associated with obesity, the presentation contributes to the advancement of scientific knowledge in the fields of obesity, weight management, and obstetrics. It stimulates further inquiry and exploration into potential therapeutic targets and interventions.
