The thymus is where T cells mature, the training ground for the footsoldiers of the adaptive immune system. As the thymus declines in size and function with age, the supply of new T cells falls. This constrains and distorts the existing population of T cells, resulting eventually in chronic inflammation and immunosenescence, the failure the immune response and resulting vulnerability to pathogens and cancer. Atherosclerosis, meanwhile, is a condition of the innate immune system, in that it is caused by macrophages - a type of innate immune cell with origins that have nothing to do with the thymus - flocking to try and fail to remove deposits of cholesterol from blood vessel walls. The resultant dysfunction and death of those macrophages generates growing plaques of fat and cell debris that narrow and weaken blood vessels.

Given these two quite separate sets of mechanisms, what is the link between the two? The answer is chronic inflammation. The processes of atherosclerosis respond strongly to inflammation, as inflammatory signaling changes the behavior of macrophages for the worse. Badly behaving macrophages do less to clean up cholesterol in blood vessel walls, and may even actively make the situation worse by propagating inflammatory signals themselves. That much is straightforward and well-explored by the research community. The novel speculation in the open access paper here is a link between low-density lipoprotein and decline in thymic function, making a feedback loop of sorts. This is the first time I've seen that put forward as a hypothesis, and I have no idea as to its plausibility.

Atherosclerosis is a complex disease characterized by smooth muscle cell proliferation, cholesterol deposition, and the infiltration of mononuclear cells. The formation and progression of atherosclerotic plaques result in the disruption of organ perfusion, causing cardiovascular and cerebrovascular diseases. It has been proved that immune responses participate in every phase of atherosclerosis. There is increasing evidence show that both adaptive and innate immunity tightly regulate the development and progression of atherosclerosis.

Atherosclerosis is considered as an immune inflammatory disease, and the T cell-mediated immune inflammatory response plays an important role in the pathogenesis of atherosclerosis. T cells mature in the thymus and are involved in the process of atherosclerosis induced by inflammation and immune response. Inflammatory mechanisms and immune system mechanisms are crucially involved in the pathophysiology of atherosclerosis and cardiovascular disease. T lymphocytes are involved and play an important role in both the inflammatory response and the immune response. An imbalance of the degree of activation of the protective Treg lymphocytes, the pro-inflammatory and cytotoxic macrophages and T-effector lymphocytes could thus be at the origin of the triggering or not of progression of vascular injury. However, all of these processes are closely associated with thymus function. In other words, changes in the function of thymus will be deeply affecting the process.

Based on previous research, we can speculate that the changes of thymus function may have an impact on the process of atherosclerosis. The mechanism of thymus involvement in the process of atherosclerosis is assumed as follows: Low density lipoprotein or cholesterol reduces the expression of the thymus transcription factor Foxn1 via low density lipoprotein receptors (LDLR) on the membrane surface and low density lipoprotein receptor-related proteins on the cell surface, which cause the thymus function decline or degradation. The imbalance of T cell subgroups and the decrease of naive T cells due to thymus dysfunction cause the increase or decrease in the secretion of various inflammatory factors, which in turn aggravates or inhibits atherosclerosis progression and cardiovascular events. NK T cell, dendritic cells, and macrophages can affect the process of atherosclerosis by affecting the production of naive T cells through the thymus. Furthermore, these cells can also participate in the progression of atherosclerosis via the direct secretion of cytokines or inducing other cells to secrete cytokines.

According to our hypothesis, various biotechnologies can be selected to improve aging thymus function in animal experiments. In the clinical treatment of atherosclerosis, and even other immune-related diseases, we may consider improving the expression of foxn1 in the human body, thereby improving or restoring aging thymus function and resisting the related-diseases caused by the decline of immunity. Further investigation on changes of thymus function will help to develop new therapeutic targets that may improve outcomes in atherosclerosis and cardiovascular disease and discover novel approaches in the treatment of atherosclerosis and vascular disease.