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Research assistant Michael Hutton, from the Heart Research Institute (HRI) Atherosclerosis and Vascular Remodelling Group, and his supervisor Dr Ashish Misra have published a paper on the role of vascular cell plasticity in atherosclerosis in the latest issue of Clinical Therapeutics.

This review, titled ‘New Targets in Atherosclerosis: Vascular Smooth Muscle Cell Plasticity and Macrophage Polarity’ was conducted in collaboration with Prof Sanjay Patel, leader of the Coronary Diseases Group at HRI, along with PhD student Alexander Lin and Honours student Madeleine Frazer, with Michael as co-first author.

Atherosclerosis, the main underlying cause of cardiovascular disease (CVD), remains the leading cause of premature death worldwide and the development of innovative new therapies is critical.

It is a disease in which plaques that are made up of fat, cholesterol, calcium and other substances build up in the walls of arteries. It is most serious when it occurs in arteries to the heart or to the brain, as this can lead to heart attack or stroke.

Macrophages and smooth muscle cells (SMCs) are major contributors to the plaque growth – and the cell phenotypes derived from these are increasingly becoming recognised for their role in the disease.

The development of new techniques, like genetic fate-mapping and transcriptomics, have allowed researchers to have a better understanding of atherosclerotic plaque – and the nature of SMCs and macrophages.

The published article is a comprehensive review of such studies and shows that vascular cell plasticity remains a promising and relatively unexplored target to treat atherosclerosis.

The researchers conclude that SMC plasticity and macrophage polarity may provide unique therapeutic options to treat CVDs.

“This approach may prove to be cru­cial in reduc­ing car­dio­vas­cu­lar events and improv­ing patient ben­e­fit in the future,” the researchers said.

The highlights of the paper include the following.

  • Cell phenotypes derived from vascular SMCs and macrophages can be both detrimental and beneficial when it comes to atherosclerosis.
  • These vascular cell phenotypes are determinants of plaque structure – and therefore highly likely to influence clinical outcomes.
  • The increasing weight of evidence about the role of SMC plasticity and macrophage polarity in plaque vulnerability provides a strong foundation for new treatments.
  • The approach may prove crucial to reduce CVD and improve patient benefits.

Clinical Therapeutics is an international peer-reviewed journal of recent developments in drug therapy, published by Elsevier.

Michael completed a Masters degree in biochemistry at the University of Canterbury in Christchurch, New Zealand and has been an RA at HRI since May 2022.

Michael was brought to HRI through the New Zealand Pathways to PhD program - an exciting opportunity for NZ postgraduate students considering a career in medical research.

Header image: (from left to right) Alexander Lin, Dr Ashish Misra, Michael Hutton.


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