One step closer to understanding atherosclerosis

HRI’s Atherosclerosis and Vascular Remodelling Group led by Dr Ashish Misra, together with the Coronary Diseases Group led by Prof Sanjay Patel, is investigating the process that drives pathogenesis in atherosclerosis and has published a review in the internationally acclaimed publication Arteriosclerosis, Thrombosis, and Vascular Biology.

The review provides an overview of cell clonality in atherosclerotic progression, focusing particularly on smooth muscle cells (SMCs) and macrophages. It discusses key findings from the latest research that give insight into the mechanisms by which clonal expansion of vascular cells contributes to disease pathology.

To provide further background, most cases of heart attack and stroke
are caused by a rupture of unstable atherosclerotic plaque. Vascular cells are key in this process, particularly SMCs and macrophages.

SMCs migrate into the atherosclerotic plaque from the blood vessel wall, where they help to form a fibrous cap that stabilises the plaque.

In contrast, macrophages contribute to inflammation within the plaque and erode the fibrous cap, which leads to instability and rupture of the plaque. At this point, individual SMCs can divide inside the plaque. This is also known as clonal expansion or clonality, where clones are the descendants of a single cell. Some of these descendants stop behaving like SMCs, a process also known as phenotypic switching, and can start behaving like macrophages.

Dr Misra’s review is of key importance because little is currently known about how clonal expansion of vascular SMCs and macrophages contribute to atherosclerosis.

He sheds light on the interplay between how SMCs build the fibrous cap on plaque, but can switch to behave like macrophages and contribute to an inflammatory process inside the plaque. Increasing our knowledge will enable understanding of how clonal cells suppress migration and proliferation of neighbouring cells in plaques.

This review advances our understanding of atherosclerosis and lays the groundwork towards a future direction for clinical therapy for atherosclerosis. This could ultimately help prevent and treat heart attack and stroke.

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