Thanks, Maya! we need to develop: 1) testing of ImP in blood samples; 2) treatments for people with high ImP to inhibit its sensing (as in the paper) or its production (by inhibiting bacterial UrdA enzyme). Ideally, along with other treatments (e.g. potential synergy with lipid-lowering treatments).

Many thanks, Luis! 🫂 @lferreiramoita.bsky.social

Thanks for the post, Ivan @lozanzi.bsky.social ! 🫂

Gracias!!! 🤗🤗🤗

Thanks, Toño!!! 🫂

¡Gracias Carlos! 😊

🙏🏻Main funding by @caixaresearch.bsky.social (1M€).
Additional support by @ageinves.bsky.social @erc.europa.eu ERC-2016-Consolidator Grant 725091; ERC-2023-PoC;
Other funders: @comunidadmadrid.extwitter.link @contracancerinv.bsky.social @worldwidecancer.bsky.social
DOI nature.com/articles/s41...

📝 Study led by @annalaura-m.bsky.social & @iroblesv.bsky.social
🙏🏻collab #CNIC_CARDIO, #Borjaibanez1 starting this with me 7 years ago, Valentin Fuster, Fredrik Bäckhed on all ImP work, Göran Bergström IGT cohort, Kostas Stellos, Gabriel Nuñez Coral Barbas & many other col.

🧪 ImP is a circulating biomarker of early and active #atherosclerosis, with diagnostic and therapeutic potential.
📉 Its effects are lipid-independent: ImP–I1R–mTOR axis in myeloid cells as a new therapeutic target for atherosclerosis. Synergy with lipid-lowering therapy?
#immunosky #cardiosky

🧠 Mechanism: ImP acts through the imidazoline receptor I1R (Nischarin) in myeloid cells, activating mTOR and inducing TNF production.
🧬 Genetic or pharmacological blockade of I1R prevents #atherosclerosis development without lowering cholesterol.
#immunosky #cardiosky #microbiomesky

🐭 In mice, oral ImP administration is sufficient to drive #atherosclerosis, without altering cholesterol or glucose.
🧪 It triggers #innate and #adaptive #immune activation and systemic inflammation.
#immunosky #cardiosky #microbiomesky

In two independent human 🚶‍♀️🚶‍♂️cohorts (PESA @CNIC_CARDIO and IGT), plasma ImP levels were higher in people with subclinical #atherosclerosis, defined by multimodal advanced imaging (ultrasound, CT, PET-FDG). ImP linked to ACTIVE atherosclerosis in PESA.
#immunosky #cardiosky #microbiomesky

🔬 Using #untargeted #metabolomics in #atherosclerosis-prone mice, we identified ImP as strongly associated with plaque formation, even in the absence of cholesterol changes.
🦠 ImP concentration depend on gut #microbiota composition.
#immunosky #cardiosky #microbiomesky

Thank you to my co-author @iroblesv.bsky.social and
@sancholab.bsky.social for believing in this project and to all the researchers who contributed to this work!!

Thanks, Christian! many years of team effort! 🫂