Talk abstracts
Talk on Saturday 11:00-11:15am submitted by Warlley Cunha
CASC15 lncRNA as a Mediator of Vascular Senescence in the Renin-Angiotensin System
Warlley Rosa Cunha (Center for Molecular Medicine and Genetics Wayne State University, Detroit, MI), Maria Martin de la Vega (Center for Molecular Medicine and Genetics,Wayne State University, Detroit, MI), Anika Kulkarni (Michigan State University, East Lansing, MI), Delphine Gomez (University of Pittsburgh. Pittsburgh. PA), Cristina Espinosa-Diez (Center for Molecular Medicine and Genetics,Wayne State University, Detroit, MI)
Abstract:
The renin-angiotensin system regulates vascular function and maintains blood pressure homeostasis. Angiotensin-II (Ang-II) and angiotensin-1-7 (Ang-1-7) have opposing effects on vascular health. Ang-II promotes vascular senescence and pathophysiological remodeling by inducing oxidative stress, inflammation, vascular hypertrophy, and endothelial dysfunction. In contrast, Ang-1-7, known for its vasodilatory, anti-inflammatory, and antioxidative properties, counteracts these detrimental effects. Our lab has characterized CASC15, a lncRNA enriched in vascular smooth muscle and endothelial cells, which has been shown to influence cellular responses to stress. Previous findings demonstrated that Ang-II reduces CASC15 expression in vascular smooth muscle cells (SMCs), promoting senescence. However, the ability of Ang 1-7 to reverse this effect by restoring CASC15 expression requires further investigation. We treated mouse SMCs with Ang-II, and other cellular stressors such as hydrogen peroxide (H2O2) and doxorubicin to assess CASC15 expression through RT-qPCR. CASC15 expression decreased significantly following Ang-II treatment, while co-treatment with Ang 1-7 restored CASC15 expression beyond control levels. H2O2 and doxorubicin also reduced CASC15 expression. To examine the impact of CASC15 loss, SMCs were transfected with an antisense oligonucleotide to suppress CASC15 expression, and DNA damage was evaluated, resulting in increased γH2AX foci, indicating elevated DNA damage. Ang 1-7 prevented DNA damage in both control and CASC15-inhibited cells. In conclusion, CASC15 is a crucial SMC regulator, and its loss promotes vascular senescence, hypertrophy, and DNA damage, effects countered by Ang-1-7. Targeting CASC15 could offer new strategies for mitigating vascular aging and improving vascular health, particularly chronic kidney disease. Future work will focus on the role of CASC15 responses in hypertensive remodeling in vivo.
Keywords: LncRNAs, senescence, Angiotensin