Exercise Reduces Inflammatory Leukocyte Production, Slowing Development of Atherosclerosis

Researchers here report on the investigation of a lesser known mechanism by which exercise lowers risk of cardiovascular mortality. It alters cell signaling that drives the creation of inflammatory immune cells, and in turn thus accelerates the development of atherosclerosis. Atherosclerosis is the buildup of fatty deposits called plaques that narrow and weaken blood vessels, leading to heart attack and stroke. It is a condition resulting from dysfunction in the innate immune cells called macrophages that are responsible for clearing out fats from blood vessel walls. Once atherosclerosis has started, chronic inflammation from any source will accelerate its progression, by making it even harder for macrophages in an atherosclerotic plaque to adopt the set of behaviors required to help clear the damage.

Researchers examined how physical activity affects the activity of bone marrow, specifically hematopoietic stem and progenitor cells (HSPCs). HSPCs can turn into any type of blood cell, including white blood cells called leukocytes, which promote inflammation. The body needs leukocytes to defend against infection and remove foreign bodies. But when these cells become overzealous, they start inflammation in places where they shouldn't, including the walls of arteries.

Researchers studied a group of laboratory mice who were housed in cages with treadmills. Some of the mice ran as much as six miles a night on the spinning wheels. Mice in a second group were housed in cages without treadmills. After six weeks, the running mice had significantly reduced HSPC activity and lower levels of inflammatory leukocytes than other mice who simply sat around their cages all day. Exercising caused the mice to produce less leptin, a hormone made by fat tissue that helps control appetite, but also signals HSPCs to become more active and increase production of leukocytes. In two large studies, the team detected high levels of leptin and leukocytes in sedentary humans who have cardiovascular disease linked to chronic inflammation.

Reassuringly, the study found that lowering leukocyte production levels by exercising didn't make the running mice vulnerable to infection. This study underscores the importance of regular physical activity, but further focuses on how mechanisms by which exercise dampens inflammation could lead to novel strategies for preventing heart attacks and strokes.

Link: https://www.eurekalert.org/pub_releases/2019-11/mgh-she110619.php

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