Lamin A/C expression in hematopoietic cells declines during human aging and constrains atherosclerosis in mice

Aging is the main risk factor for atherosclerotic cardiovascular disease, a condition caused by immune cells that leads to the buildup of plaques in arteries and is the top cause of death worldwide. Earlier studies on premature aging diseases have linked this condition to problems with A-type lamins, important parts of the cell's nuclear envelope. In this study, we looked at how aging changes the levels of lamin A/C in white blood cells and how changing these levels in blood-forming cells affects their behavior and the development of atherosclerosis Atheroprone Ldlr-/- mice were used as recipients in BM transplantation (BMT) experiments. During 4 weeks after BMT, mice were on standard diet for BM reconstitution and then placed on a high-fat diet (HFD) for 6 weeks to induce hypercholesterolemia and atherosclerosis development. Mouse studies were conducted with male and female 8-14 week old, except for BMT with lamin A/C-null BM, which was obtained from 3–4 week old. Experimental groups are: 1) WT BM, mice transplanted with WT BM donors 2) Lmna-/- BM, mice transplanted with BM from donors lacking lamin A/C ubiquitously. 3) Lmnatg BM, mice transplanted with BM from Lmnatg silent donors. 3) Lmna-OE BM, mice transplanted with BM from Lmnatg Overexpressing donors.