ArticleCardio-oncology (London, England)2026
Macrophage surface protein Mac-2 mediates inflammatory and stromal stress pathways in doxorubicin-induced cardiac injury.
Article in Cardio-oncology (London, England), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
1 citing paper in PubMed.
- Expression, Localization and Actions of Galectin-3: Implications in the Pathophysiology and Therapy of Cardiovascular Disease.International journal of molecular sciences · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors.
Funding
Abstract
backgroundDoxorubicin (DOX) cardiotoxicity is a major complication of cancer therapy and involves macrophage-driven inflammation and myocardial remodeling. The macrophage surface protein Mac-2 (galectin-3) is upregulated in cardiac injury, but its role in regulating macrophage function and downstream injury pathways remains undefined.
methodsWe used CRISPR/Cas9-engineered Mac-2-null macrophages to evaluate chemotaxis, cytokine gene expression, and lysosomal stress signaling in vitro. To examine paracrine injury mechanisms, we performed co-culture assays with cardiomyocytes and fibroblasts. In vivo, we studied homozygous Mac-2-mutant mice and used CD45.1/CD45.2 bone marrow transplantation with lineage tracking to define hematopoietic versus stromal contributions to DOX-induced inflammation, apoptosis, fibrosis, and systolic dysfunction.
resultsDoxorubicin induced Mac-2 and inflammatory transcripts (Il6, Tnf, Ccl2) in wild-type macrophages, whereas Mac-2 knockout reduced DOX uptake, chemotaxis, and cytokine induction. In co-culture, DOX-treated WT macrophages increased caspase-3/7 activity in cardiomyocytes and phospho-TFEB in fibroblasts, both attenuated with Mac-2 deletion. In vivo, Mac-2-null mice exhibited less cardiac inflammation, apoptosis, and fibrosis with preserved systolic function and reduced mortality. Bone marrow transplantation demonstrated that hematopoietic Mac-2 suppressed cardiac Tfeb and upregulated Sqstm1 and Tgfb1, enhancing inflammatory and apoptotic responses, whereas Mac-2-deficient marrow restored Tfeb, limited Sqstm1/Tgfb1, and protected cardiac function.
conclusionsMac-2 promotes DOX-induced cardiac injury by facilitating inflammatory activation in macrophages, driving fibroblast lysosomal stress via TFEB and SQSTM1, and augmenting caspase-3–associated apoptosis in cardiomyocytes. Loss of Mac-2 in hematopoietic cells reduces inflammation, fibrosis, and systolic dysfunction in vivo.
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.