Laura Alonso Herranz - Postdoctoral Fellowship 2022
Project summary:
How do we prevent atherosclerosis from leading to heart attack?
Laura Alonso Herranz will study the smooth muscle cells in our arteries and how we can change the composition of the atherosclerotic plaque that sits on the blood vessel wall. If the plaque ruptures, it can lead to the occlusion of the vessel and heart attack. The goal is thus to prevent atherosclerosis from leading to heart attack.
Project Title
Mechanisms regulating smooth muscle cell plasticity and atherosclerotic plaque stability
Background
In atherosclerosis, smooth muscle cells (SMC) transform to alternative mesenchymal phenotypes that help drive the formation of unstable plaques. Recent evidence suggests that SMAD7, an inhibitory member of the SMAD family, suppresses the formation of contractile SMCs.
Hypothesis
We hypothesize that SMAD7 is an important regulator of SMC phenotype in arteries and atherosclerotic plaques, determining thus lesion composition and ultimately plaque stability.
Methods
We generated an inducible SMC-specific SMAD7 KO mouse (Myh11-CreERT2;Smad7fl/fl) that we will use in an experimental model of atherosclerosis combining single-cell transcriptomic and histological analysis. In addition, we will study the functional and structural properties of the arteries using non-invasive methods for blood pressure measurement and wire myography systems.
Preliminary results
Our preliminary data indicate that suppression of SMAD7 boost the contractile and quiescent state of SMCs. If forcing changes in the balance of modulated SMC types by targeting SMAD7 (i.e. increasing the proportion of cap ACTA2+ cells versus other SMC phenotypes) proves beneficial in our experimental atherosclerosis model, it may open for a new type of anti-atherosclerotic therapy.
Laura Alonso Herranz
- MSc and PhD
- Aarhus University, Department of Clinical Medicine
Mentor:
Jacob Fog Bentzon, Associate Professor, Department of Clinical Medicine, Aarhus University
Contact: