Theory 02/Transplant & Immune Tolerance/Vascular biology
Chronic Rejection Is a Shear Response
Transplant arteriopathy is treated as immune. The vessel may be trying to restore the flow it was built for.
Chronic rejection is driven by the mismatch between the graft's design shear stress and the recipient's flow, so the disease is a remodelling response to a haemodynamic error rather than an antibody attack on the vessel wall.
01The evidence
Transplant arteriopathy thickens the intima concentrically in a pattern distinct from atherosclerosis, and the degree of thickening correlates with flow indices.
02The tension
The dominant account is antibody-mediated endothelial injury. That explains inflammation and fails to explain why the lesion is concentric and flow-dependent.
03The mechanism
Endothelium senses shear stress and remodels the wall to keep it within a set range. A graft transplanted into a circulation with different flow, or with a different calibre, is outside that range from the first day.
The intimal thickening restores the shear by narrowing the lumen, which is why the lesion progresses until flow indices normalise. Antibodies accelerate it by damaging the sensor, but the set point is haemodynamic.
04What this is not
That account makes antibody the driver. This makes shear mismatch the driver and antibody an accelerator, which predicts flow-dependent progression.
05Predictions
- P1Thickening should track the shear mismatch at implantation.
- P2Flow reduction should slow progression.
- P3Matched-calibre grafts should develop less arteriopathy at equal immunology.
06Refutation
Arteriopathy independent of shear at matched immunology would remove the haemodynamic set point.
07What it changes
It would add graft sizing and flow matching to transplant planning.