Research Spotlight: Combined therapeutic strategies to treat atherosclerosis in cardiovascular disease

Atherosclerosis is the build-up of fatty plaque deposits on the walls of the arteries in the body that lead to cardiovascular diseases (CVD) such as heart attack and stroke.

There is no cure for atherosclerosis. Medicines such as statins can reduce the 'bad' or LDL-cholesterol levels to halt its progress and reduce the risk of heart attack and stroke. However, some patients cannot tolerate statins or reach acceptable LDL-cholesterol levels on treatment. A significant proportion of statin-treated patients remain at substantial risk of CVD. 

Pictured (l-r): Tanwi Vartak, PhD student and first author; Dr Eoin Brennan, UCD School of Medicine and Fellow, UCD Conway Institute, lead author of  new research findings published in the scientific journal, Atherosclerosis.

The research team led by Dr Eoin Brennan is investigating drug combination therapies alongside statins. They 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 and examined the effects on vascular smooth muscle cell inflammation.

Vascular smooth muscle cells are one of the most abundant cell populations in the vessel wall and key cellular drivers of early and late-stage atherosclerosis.

Excessive vascular inflammation underlies virtually all pathological events in the vasculature. Targeting vascular inflammation is considered a promising therapeutic strategy for atherosclerotic cardiovascular disease. This study aimed to investigate the effects of let-7d-5p miRNA overexpression alone or in combination with the drugs, atorvastatin/lovastatin on smooth muscle cell inflammatory pathways as well as phenotypic switching.

“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.”

Journal citation
Vartak T, Giardini E, Kelly D, Moran B, Kennedy C, Barry M, Godson C, Brennan E. Induction of let-7d-5p miRNA modulates aortic smooth muscle inflammatory signaling and phenotypic switching. Atherosclerosis. 2024 Aug;395:117573. doi: 10.1016/j.atherosclerosis.2024.117573. Epub 2024 May 6. PMID: 38796407.