According to a recent Yale study, aged bone marrow encourages the growth of vascular smooth muscle cells (SMCs) and worsens the accumulation of plaque in artery walls. It is unclear what happens to arterial SMCs as bone marrow cells age.
Bone marrow cell aging explains plaque accumulation in arteries
Senior author Daniel Greif and his associates employed single-cell and clonal-cell analyses to define the effects. First study author Inamul Kabir who is an associate researcher in the Greif Lab, has previously worked on a study demonstrating how fibrotic lung disease works. In the latest work, they reveal that older people’s bone marrow encourages the growth of SMCs while aggravating atherosclerosis, the accumulation of fatty deposits termed plaques in arterial walls.
Atherosclerosis, the main cause of strokes and heart attacks, is significantly increased with age. Age-related clonal hematopoiesis of indeterminate potential (CHIP) is a process wherein mutations build up in bone marrow stem cells. Such altered stem cells produce dominant copies of inflammatory white blood cells like macrophages. CHIP has been linked to negative cardiovascular results. Atherosclerotic plaques are mostly made up of macrophages and SMCs, and scientists have previously shown how rare SMCs are drawn to the plaques and clonally expanded there.
Aging reduces the TET2 gene
In the study published in the Nature Aging journal, the researchers transplanted bone from an aged rodent to young mice and genetically altered atheropine mice to show that aged bone marrow makes SMCs enter plaques which worsens atherosclerosis. From the study, researchers discovered that aging leads to the reduction of the TET2 gene, which is responsible for age-related CHIP. Reduced TET2 levels regulate the expansion and regulation of SMCs in the plaque.
The study authors indicate that they demonstrate that older macrophages express low TET2 levels, exhibiting Itgb3 expression. In addition, they demonstrated that low integrin three levels in macrophages increase levels of tumor necrosis factor, which cause polyclonal multiplication of SMCs in atherosclerotic plaque and exacerbate the disease. Therefore, the study put forth deficient SMC clonal multiplication regulation by aged bone marrow-derived macrophages to be important in understanding atherogenesis.
