Senescent heart and aortic cells accelerated fibrin formation and slowed its breakdown in cell culture experiments
Senescent heart and aortic cells accelerated fibrin formation and slowed its breakdown in cell culture experiments
In a paper published on August 1, researchers induced senescence in cultured human heart and aortic cells. Fibrin formed faster and broke down more slowly near these cells. Rapamycin reduced the accelerated fibrin formation in the same cell culture system.
When a clot forms, thrombin converts soluble fibrinogen into fibrin. The fibrin strands assemble into a mesh that traps blood cells. During clot dissolution, tPA activates plasmin, an enzyme that cuts through this mesh.
The authors used primary human fibroblasts from the cardiac ventricle and endothelial cells that line the aorta. Doxorubicin induced senescence in these cells: they stopped dividing and changed the range of substances they secreted. After 14 days, the researchers added fibrinogen to the culture and measured how quickly it was converted into fibrin.
In senescent endothelial cells, the maximum fibrin signal increased by 16%, while in fibroblasts it increased by 26%. Thrombin activity increased by 62% and 47%, respectively. Argatroban, a thrombin inhibitor, reduced fibrin formation. The authors attribute the faster fibrin formation to increased thrombin activity.
In the clot breakdown experiment, tPA was added externally. Even so, fibrin persisted longer near senescent cells. These cells showed increased expression of PAI-1, a protein that inhibits tPA. This change is consistent with the slower fibrin breakdown observed in the same system.
In this cell model, senescence both accelerated the formation of the fibrin mesh and slowed its breakdown. Rapamycin was added during the induction of senescence and throughout the following 14 days. In senescent cells, the area under the fibrin formation curve was 23% lower in endothelial cells and 15% lower in fibroblasts. The researchers thus established two measurable outcomes that can be used to compare how interventions affect fibrin near senescent cells.