Macrophage adenylyl cyclase 7 protects against myocardial ischemia/reperfusion injury in male mice.
G, X., S, Z., Y, L., Y, S., J, C., J, P., Z, C., P, W., C, S., & A, D. (2026). Macrophage adenylyl cyclase 7 protects against myocardial ischemia/reperfusion injury in male mice.. Nature communications. https://doi.org/10.1038/s41467-026-74706-5
G X, S Z, Y L, Y S, J C, J P, et al. Macrophage adenylyl cyclase 7 protects against myocardial ischemia/reperfusion injury in male mice.. Nature communications. 2026; doi: 10.1038/s41467-026-74706-5
G X, S Z, Y L, et al. Macrophage adenylyl cyclase 7 protects against myocardial ischemia/reperfusion injury in male mice.[J]. Nature communications. 2026. DOI: 10.1038/s41467-026-74706-5.
@article{g2026,
author = {Xia G and Zhu S and Liu Y and Shi Y and Chen J and Pan J and Chen Z and Wei P and Shen C and Du A},
title = {Macrophage adenylyl cyclase 7 protects against myocardial ischemia/reperfusion injury in male mice.},
journal = {Nature communications},
year = {2026},
doi = {10.1038/s41467-026-74706-5},
note = {PMID: 42509235},
}
TY - JOUR AU - Xia G AU - Zhu S AU - Liu Y AU - Shi Y AU - Chen J AU - Pan J AU - Chen Z AU - Wei P AU - Shen C AU - Du A TI - Macrophage adenylyl cyclase 7 protects against myocardial ischemia/reperfusion injury in male mice. T2 - Nature communications PY - 2026 DO - 10.1038/s41467-026-74706-5 AN - PMID:42509235 ER -
Myocardial ischemia/reperfusion (I/R) injury undermines the clinical benefit of percutaneous coronary intervention, with cardiac macrophages playing critical roles. Here, using spatial transcriptomics and flow cytometry, we identified adenylyl cyclase 7 (ADCY7) as a macrophage-specific regulator and potential therapeutic target in myocardial I/R injury, and validated its expression in patient samples. By establishing a macrophage depletion/reconstitution model, we demonstrate that macrophage Adcy7 deficiency significantly exacerbates myocardial I/R injury and cardiac dysfunction in male mice, whereas Adcy7 overexpression attenuates these effects. Macrophage Adcy7 deficiency also increases leukocyte infiltration and pro-inflammatory cytokine production. Mechanistically, transcriptomic and phosphoproteomic analyses reveal that ADCY7 activates cAMP-protein kinase A signaling, thereby inhibiting nuclear translocation of NF-κB and restraining the pro-inflammatory response. Combined with the macrophage depletion/reconstitution approach, we developed a photoactivated adenylyl cyclase system that alleviated cardiac inflammation and I/R injury. Our study identifies ADCY7 as a macrophage-intrinsic anti-inflammatory regulator and a promising therapeutic target for myocardial I/R injury.