Cholesterol discovery could prevent cardiovascular disease and stroke

[Dec. 14, 2023: JJ Shavit, The Brighter Side of News]

Researchers at the University of Leicester, in collaboration with colleagues from the USA, China, and Australia, have made a groundbreaking discovery regarding the intricate mechanism by which cholesterol from our diet is absorbed into our cells.

This significant breakthrough, recently published in the prestigious journal Science, opens up promising avenues for therapeutic interventions that could revolutionize the control of cholesterol uptake, potentially saving lives.

Cholesterol, a natural fatty substance found in the bloodstream, plays a vital role in the human body. It is primarily synthesized in the liver and is also present in certain foods, including red meat and dairy products.

Furthermore, cooking methods like frying can contribute to the cholesterol content of our diets. While cholesterol is necessary for various bodily functions, an excess of it, known as high cholesterol, can lead to the accumulation of fatty deposits in arteries, increasing the risk of heart disease.

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The research, generously funded by the Leducq Foundation, which awarded $6 million to eight laboratories across the USA and Europe for collaborative research into cholesterol transport within the human body, has unveiled the pivotal role of two proteins, Aster B and Aster C, in facilitating the transport of cholesterol.

These proteins are instrumental in shuttling cholesterol from the cell membrane of the intestinal lining to an internal compartment where it undergoes modification before entering circulation.

Professor John Schwabe, Director of the Institute for Structural and Chemical Biology at the University of Leicester, emphasized the significance of this discovery, stating, "This breakthrough is the result of a long-lasting collaboration and forms part of an international effort to identify ways in which we can combat cardiovascular disease and stroke.

A better understanding of important areas of cholesterol absorption and metabolism and, particularly, how cholesterol moves within cells and tissues is essential. This knowledge will allow us to design new drugs and therapies that target specific proteins involved in these pathways to combat most pressing public health problems such as heart attacks and stroke."

One of the key highlights of this research is its potential to pave the way for innovative therapeutic strategies to control cholesterol absorption. The team at the University of Leicester used their expertise to explore how Ezetimibe, a cholesterol-lowering drug, effectively blocks the ability of Aster B and Aster C to transport cholesterol. By gaining insights into these mechanisms, researchers hope to develop targeted therapies that can prevent excessive cholesterol from being absorbed into cells, thereby reducing the risks of heart disease and stroke.

Professor Schwabe added, "If we can prevent some cholesterol from being absorbed into our cells, we may ultimately be able to prevent individuals from having high cholesterol and cut down their risks of heart attack and stroke and therefore potentially save lives."

This research is part of a broader collaborative effort by the Leducq team, which comprises experts with diverse skills aimed at tackling the issue of cholesterol absorption from various angles. In addition to targeting cholesterol absorption, the team is investigating how cholesterol metabolism and transport impact cholesterol levels and atherosclerotic disease. Cholesterol transporters are essential in regulating blood cholesterol levels, making them prime targets for drug development aimed at lowering the risk of heart attack and stroke.

Postdoctoral Researcher, Dr. Beatriz Romartinez-Alonso, expressed her enthusiasm for the project, stating, "This has been a great project to work on - discovering new science highly relevant to human health."

The implications of this research extend far beyond the laboratory. Cardiovascular disease remains a leading cause of death globally, and high cholesterol levels are a significant risk factor for its development. Therefore, any breakthrough that sheds light on the mechanisms behind cholesterol absorption and transport holds the potential to revolutionize preventive and therapeutic strategies.

Cholesterol is not only synthesized within our bodies but is also introduced through our diet. Understanding how this dietary cholesterol is absorbed and processed within our cells is crucial for developing targeted interventions. With the newfound knowledge of the roles played by Aster B and Aster C proteins in cholesterol transport, researchers are now better equipped to devise strategies that could reduce the risk of heart attacks and strokes, ultimately saving lives.

The Leducq Foundation's generous funding has enabled an international collaboration of scientists to pool their expertise and resources, amplifying the impact of this research. By examining cholesterol absorption and transport at multiple levels and from various angles, these researchers are advancing our understanding of cholesterol-related diseases and paving the way for the development of innovative therapies.

Ezetimibe, the cholesterol-lowering drug investigated in this study, has already demonstrated its efficacy in blocking cholesterol transport proteins. This presents a promising avenue for the development of drugs that can specifically target Aster B and Aster C, ultimately reducing the absorption of dietary cholesterol into our cells.

The global burden of cardiovascular disease is a pressing public health challenge. High cholesterol levels are a modifiable risk factor for heart disease, and controlling cholesterol absorption represents a promising approach to reducing this risk. The discoveries made by the University of Leicester researchers, in collaboration with their international colleagues, represent a significant step forward in our understanding of cholesterol metabolism.

The research conducted by the University of Leicester sheds light on the intricate mechanism by which cholesterol in our diet is absorbed into our cells. This discovery opens up exciting opportunities for therapeutic interventions that could revolutionize the control of cholesterol uptake, potentially saving lives in the process. With the support of the Leducq Foundation's generous funding, researchers are forging ahead in their quest to unravel the complexities of cholesterol absorption and transport, offering hope for a future with reduced rates of heart disease and stroke.

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