https://doi.org/10.1007/s00392-025-02625-4
1Universität zu Lübeck Institut für Kardiogenetik Lübeck, Deutschland; 2Zentrum für Innere Medizin III. Medizinische Klinik und Poliklinik (Nephrologie/Rheumatologie/Endokrinologie) Hamburg, Deutschland
BACKGROUND:
Hypertension, a significant risk factor for cardiovascular diseases, is increasingly associated with inflammation. Various hypertensive stimuli cause monocyte/macrophage infiltration into tissues like the heart and kidneys, promoting inflammation and thereby exacerbate hypertension. CRIP1 has been identified to be associated to blood pressure in human monocytes, and recent findings suggest altered CRIP1 expression in monocytes from hypertensive mice. However, its precise role in hypertension-related inflammation remains unknown.
AIM:
This project aimed to investigate the role of CRIP1 in regulating monocyte migration and infiltration, focusing on its potential impact on hypertension-related inflammation.
METHODS:
Monocyte-like THP-1 cells with shRNA-mediated CRIP1 knockdown (>70% reduction) were compared to control cells to assess their migration and infiltration capabilities. Migration in response to chemoattractants was evaluated using transwell assays, while infiltration ability was assessed using kidney organoids derived from human induced pluripotent stem cells iPSCs, which serve as an organ model to simulate immune cell infiltration into tissues. This organoid-based model was specifically chosen to mimic the physiological environment of organs, allowing for a more relevant assessment of monocyte infiltration capabilities into organ-like structures.
RESULTS:
Knockdown of CRIP1 in THP1 monocytes resulted in an approximately 50% reduction in migration ability in response to increasing concentrations of migratory stimuli compared to control cells, as assessed by transwell assays. Infiltration assays demonstrated that CRIP1 knockdown significantly reduced the infiltration capability of THP-1 cells into kidney organoids. Control cells exhibited markedly increased infiltration in the presence of MCP1 or AngII, whereas CRIP1 knockdown cells showed substantially reduced infiltration despite MCP1 or AngII stimulation.
CONCLUSION:
Our results indicate that CRIP1 is crucial for regulating monocyte migration and infiltration, highlighting its potential as a therapeutic target for hypertension-related inflammation. Further studies are necessary to understand how CRIP1 modulates these processes, which could lead to targeted therapies aimed at reducing inflammation and preventing cardiovascular complications in hypertensive patients, given that chronic inflammation and monocytic infiltration play significant roles in this condition.