Dublin, Ireland - A new study “Induction of Let-7d-5p miRNA modulates aortic smooth muscle inflammatory signaling and phenotypic switching.” published in Atherosclerosis conducted by researchers in the Brennan lab, University College Dublin (UCD) has yielded promising results in the fight against cardiovascular diseases (CVDs), one of the leading causes of death and disability in Ireland.
The research, led by Dr. Eoin Brennan, focused on a specific type of RNA molecule, let-7d-5p, which was found to be present at lower levels in patients with advanced atherosclerosis, a condition characterised by fatty plaque build-up in arteries. Previous studies (by Dr. Brennan's lab) have shown that by increasing let-7d-5p levels in vascular tissue, this led to reduced inflammation, a key driver of CVD progression. Dr. Brennan commented, “We are excited that this type of RNA therapy could potentially be used in combination with statins to reduce the risk of atherosclerotic CVD.”
This paper was supported by a UCD Ad Astra Fellowship (Eoin Brennan - PI & senior author), UCD Ad Astra PhD studentship (Tanwi Vartak - first author) and Science Foundation Ireland Awards. Elena Giardini (co-author) participated in this study during her Student Summer Research Awards (SSRA) project and is a recent UCD Biomedical Health & Life Sciences (BHLS) graduate who has started her PhD in the Brennan lab. Daniel Kelly (co-author) is also a recent UCD BHLS graduate who participated in this study during his BHLS project placement. Daniel is now embarking on his medicine studies at UCD through the Graduate Entry Medicine (GEM) course. The research team collaborated with Prof Mary Barry, Vascular Surgeon, St. Vincent's University Hospital and Prof Catherine Godson (UCD Diabetes Complications Research Centre).
CVDs are among the leading causes of death and disability in Ireland, and can be caused by a build-up of fatty plaque deposits on the walls of the arteries (termed - atherosclerosis). The rising global prevalence of obesity and diabetes has exacerbated this further in the past decade. There is no cure for atherosclerosis but we can halt its progress and prevent heart attack and stroke by using medicines such as statins which act by reducing your LDL-cholesterol levels. The problem is that a significant proportion of statin-treated patients remain at substantial risk of CVD, and some patients cannot tolerate statins or reach acceptable LDL-cholesterol levels on treatment. One possible solution to improve the use of statins is to apply a stratified treatment strategy involving the tailoring of type and dosage of statin, as well as investigating drug combination therapies alongside statins.
This new study explored the potential of combining statin therapy, the current standard treatment for management of high cholesterol in CVD, with let-7d-5p RNA therapy. “Our data shows for the first time that combining these approaches leads to a more pronounced anti-inflammatory effect,” said Dr. Brennan. “This suggests that such combination therapies could be of great benefit to patients who are not effectively managed by statins alone.”
The findings offer significant hope for a future where RNA therapy can be used alongside existing treatments to improve patient outcomes. However, further research is needed. “The next challenge,” explains Dr. Brennan, “is to test this treatment in longer-term models and develop methods to deliver the RNA therapy specifically to vascular lesions.”
The research team acknowledges the crucial role of funding in their work. “We are grateful for the support of UCD Ad Astra Fellowships and Science Foundation Ireland grants,” said Dr. Brennan. “These awards were instrumental in allowing us to complete this study.”
The study also highlights the valuable contributions of undergraduate researchers. “It was a pleasure to collaborate with Elena Giardini and Daniel Kelly during their undergraduate studies,” said Dr. Brennan. “Their work in the lab provided important data, showcasing the exceptional calibre of our BHLS graduates. We are thrilled to see Elena continuing her research as a PhD candidate in our lab and Daniel embarking on his medical studies at UCD.”