A new study published in BMC Genomics by Liang-Hao Ding of The University of Texas Health Science Center at Tyler and UT Southwestern Medical Center, together with Michael D. Story, Shoukath Sulthana, R Burke Squires, Elijah F. Edmondson, Michael M. Weil and colleagues, addresses this question at the level of whole genomes. The team performed whole genome sequencing on hepatocellular carcinoma (HCC), the most common form of primary liver cancer, that arose in mice after exposure to heavy-ion particle radiation or gamma-ray radiation, and compared the resulting mutational profiles with those of spontaneously arising liver tumors. Their goal was to identify genomic features that could serve as fingerprints of radiogenic cancer, and in particular of cancers caused by the HZE ions that dominate the deep-space radiation field.

The choice of experimental model is a critical part of the study’s design. Laboratory cancer experiments have traditionally relied on inbred mouse strains, which offer genetic uniformity but poorly reflect the genetic heterogeneity of human populations. In this work, the researchers used outbred mice, whose genomes carry a broad mosaic of genetic variants similar to the diversity seen in humans. This genetically diverse background provides a more realistic substrate for tumor development, allowing cancers to emerge through the interplay of random mutations, environmental insults and individual genetic susceptibility. An earlier study using the same model had already revealed a wide spectrum of cancer histotypes linked to different types of ionizing radiation, with hepatocellular carcinoma emerging as one of the most prevalent solid tumors following HZE ion exposure. That observation made radiation-associated HCC a natural target for deeper genomic interrogation.

The sequencing effort focused on three complementary layers of genomic information. The first was tumor mutation burden, or TMB, the total number of somatic mutations accumulated in a tumor’s genome. Mutation burden is a coarse but informative metric: radiation, particularly high linear energy transfer (LET) radiation, tends to inflict dense, clustered DNA damage that can elevate mutation counts above what spontaneous processes produce. The second layer was mutational signatures, the characteristic patterns of base substitutions and other mutation types that different mutagenic processes imprint on the genome. Just as forensic scientists match bullets to specific weapons, cancer geneticists decompose a tumor’s mutation catalogue into signatures attributable to specific causes, from ultraviolet light to tobacco smoke to defective DNA repair. The third layer comprised regions of hypermutation, localized stretches of the genome where mutations cluster at rates far exceeding the background, often marking sites of catastrophic or localized DNA damage and repair.

Across these layers, the analysis revealed both shared genomic features and distinct characteristics associated with the different radiation types. Radiation-associated tumors differed from spontaneous ones in their mutation burdens, their signature compositions and their hypermutation landscapes, and within the radiation-exposed group there were features that separated HZE-induced tumors from gamma-ray-induced ones. This distinction matters scientifically because gamma rays, as low-LET photons, produce sparse ionizations similar to X-rays, whereas HZE ions produce dense ionization tracks. If the genomic consequences of these two exposure types can be reliably separated, it opens the possibility of reading a tumor’s genome as a dosimeter of sorts, inferring not just that radiation played a role in its genesis but which kind of radiation was responsible.

One of the most striking findings concerns the gene Ctnnb1, which encodes beta-catenin, a central component of the Wnt signaling pathway that governs cell proliferation, differentiation and liver homeostasis. In human medicine, activating mutations in CTNNB1 are a well-known hallmark of non-viral, well-differentiated hepatocellular carcinoma, and they carry prognostic and diagnostic significance. In the mouse study, beta-catenin emerged as one of the most frequently mutated genes in the radiation-associated HCCs, mirroring its prominence in the human disease. By contrast, the spontaneous tumors showed a significantly lower frequency of Ctnnb1 mutation. This asymmetry suggests that radiation-driven liver carcinogenesis in this model converges on the same beta-catenin pathway that human non-viral HCC commonly exploits, while spontaneous tumors in these mice take other routes to malignancy. The convergence strengthens the translational relevance of the model, indicating that the radiation-induced mouse tumors recapitulate a molecular feature of the human cancers that mission planners ultimately care about.

The study also uncovered a chromosomal structural variant affecting the Cdk6 gene specifically in tumors from HZE-irradiated animals. CDK6 is a cyclin-dependent kinase that drives progression through the G1 phase of the cell cycle, and its dysregulation through amplification, translocation or altered regulation is a recognized mechanism of unchecked proliferation in several human cancers. Structural variants of this kind, which rearrange chromosomal segments rather than simply altering single DNA bases, are precisely the type of damage expected from the clustered, complex DNA breaks that dense ionization tracks produce. When a high-charge particle traverses the double helix, it can generate multiple breaks in close proximity, and the cell’s repair machinery, in stitching the fragments back together, can join the wrong ends, producing deletions, inversions, translocations and other rearrangements. Finding a Cdk6-affecting structural variant in the HZE group, and not in the comparison tumors, is consistent with this mechanistic picture and provides a candidate marker of heavy-ion exposure.

The broader implications of the work extend in two directions. For radiation biology, the results suggest that radiogenic hepatocellular carcinoma possesses unique genomic features, some of which are specifically tied to HZE radiation, offering a mechanistic window into how dense ionization tracks sculpt the cancer genome differently from sparse ionizations. For spaceflight risk assessment, the findings carry direct translational relevance. NASA’s cancer risk models for astronauts currently rest on thin empirical foundations, because epidemiological data for human HZE exposure are essentially limited to occupational cohorts such as atomic bomb survivors and radiation workers, whose exposures were predominantly low-LET. Experimental systems like the outbred mouse model used here, funded through NASA’s Specialized Center of Research on Radiation Carcinogenesis (NSCOR) program, help fill that gap by generating tumors under controlled, space-relevant exposure conditions and by supplying the genomic data needed to validate or refine risk extrapolations from mice to humans.

The technical infrastructure behind the study is also worth noting. Whole genome sequencing of multiple tumors, particularly from outbred animals whose reference-guided read alignment is complicated by genetic diversity, demands substantial computational resources. The authors acknowledge the support of the BioHPC facility at UT Southwestern and the Texas Advanced Computing Center, as well as the NASA Space Radiation Laboratory, where the radiation exposures were delivered. The work was funded by the NASA NSCOR programs under award NNX15AK13G, and all animal procedures were approved by the Colorado State University Institutional Animal Use and Care Committee. The article, published open access on 30 September 2026, was received in June 2025 and accepted in August 2026, reflecting the extended timeline typical of large-scale sequencing studies.

As human spaceflight moves from low Earth orbit toward the Moon and eventually Mars, the stakes of radiation carcinogenesis research rise accordingly. A round trip to Mars could expose crew members to doses and radiation qualities for which no human epidemiological data exist, and liver cancer, as this study shows, is among the malignancies that heavy-ion exposure promotes in a genetically diverse mammalian model. The mutational fingerprints described by Ding and colleagues, from elevated tumor mutation burdens and distinctive signatures to hypermutation regions, frequent beta-catenin mutation and HZE-specific structural variants affecting Cdk6, provide both a mechanistic foundation and a practical toolkit. If future studies confirm that these features reliably distinguish radiation-induced tumors, clinicians and researchers could one day examine a tumor’s genome and infer the radiation quality behind it, while mission designers could use the same knowledge to build more accurate cancer risk models and to develop shielding and countermeasure strategies grounded in the actual genomic consequences of the radiation astronauts will face.

Subject of Research: Mutational profiles of radiation-induced hepatocellular carcinoma in outbred mice exposed to heavy-ion and gamma-ray radiation

Article Title: Mutational profiles of hepatocellular carcinoma that arose in outbred mice after heavy-ion particle and γ-ray radiation

Article References: Ding, L.-H., Story, M. D., Sulthana, S., Squires, R. B., Edmondson, E. F., & Weil, M. M. (2026). Mutational profiles of hepatocellular carcinoma that arose in outbred mice after heavy-ion particle and γ-ray radiation. BMC Genomics. https://doi.org/10.1186/s12864-026-13304-7

Image Credits: AI Generated

DOI: 10.1186/s12864-026-13304-7

Keywords: space radiation, HZE ions, hepatocellular carcinoma, whole genome sequencing, mutational signatures, tumor mutation burden, beta-catenin, Cdk6, outbred mice, radiation carcinogenesis, liver cancer, NASA

The research team, working at the Korea Research Institute of Bioscience and Bioscience-affiliated laboratories, took an approach that sidesteps a long-standing obstacle in the field. Bone marrow from children with Legg-Calvé-Perthes disease is scarce and difficult to study, and even when mesenchymal stromal cells, the body’s principal skeletal progenitors, are isolated from osteonecrotic bone, they carry the imprint of a diseased, inflamed, poorly perfused tissue environment. Any abnormality observed in such cells could reflect that hostile microenvironment rather than an intrinsic flaw. To separate the two, the researchers reprogrammed skin fibroblasts from two patients with the disease, and from a healthy donor, into induced pluripotent stem cells using a non-integrating Sendai virus system that delivers the reprogramming factors OCT4, SOX2, KLF4 and c-MYC. Because skin cells can be reset to an embryonic-like state and then steered into mesenchymal stem cells under identical, standardized conditions, any difference that emerges between patient-derived and healthy cells must be written into the cells themselves rather than imposed by the tissue around them.

The quality control on this cellular reset was rigorous. The resulting induced pluripotent stem cell lines formed compact colonies with the characteristic morphology of embryonic stem cells, stained strongly for alkaline phosphatase, and expressed the canonical pluripotency markers OCT4, NANOG, TRA-1-60, TRA-1-81, SSEA-3 and SSEA-4 at levels comparable across all three lines. Quantitative PCR confirmed expression of OCT4 and REX1 in the undifferentiated state, and when the cells were allowed to spontaneously differentiate into embryoid bodies, they activated ectodermal markers such as SOX1 and PAX6, mesodermal markers including HAND1 and PDGFRA, and endodermal markers SOX7 and AFP. Immunostaining for TUJ1, NESTIN, DESMIN, alpha-SMA, FOXA2 and SOX17 confirmed protein-level differentiation into all three germ layers, and teratoma assays in immunodeficient mice produced tissues representing ectoderm, mesoderm and endoderm. G-band karyotyping showed normal diploid chromosomes in every line, ensuring that any phenotype found later was not an artefact of culture stress or genomic instability.

With validated stem cell lines in hand, the team differentiated them into induced mesenchymal stem cells using a defined, xeno-free protocol, first patterning the cells toward the mesodermal lineage for four days and then maturing them for a further seventeen days on fibronectin-coated plates. Flow cytometry confirmed that the resulting cells expressed the canonical mesenchymal markers CD73 and CD105 and lacked the haematopoietic markers CD34 and CD45, consistent with bona fide MSC identity. One subtlety stood out: the two patient-derived lines expressed CD90, a surface glycoprotein involved in adhesion and MSC immunophenotype, at only about sixty to seventy percent of the level seen in healthy donor cells, which reached roughly ninety-five percent. Proliferation rates, however, were indistinguishable between the groups, meaning the patient cells grew normally even as they showed this subtle phenotypic deviation, hinting that the real differences lay deeper, in what the cells could become rather than how fast they could multiply.

What the cells could become turned out to be the central finding. Under osteogenic induction, healthy donor cells produced abundant mineralized matrix, revealed by intense Alizarin Red S staining, and strongly upregulated the osteoblast genes RUNX2 and BGLAP. Both patient-derived lines formed dramatically fewer mineral deposits and mounted only weak induction of the same genes. Adipogenesis fared no better: healthy cells accumulated plentiful lipid droplets stained by Oil Red O and induced the adipogenic regulators PPARG and ADIPOQ, while patient cells showed markedly reduced lipid accumulation and gene induction. Chondrogenesis, assessed by Alcian Blue staining of sulfated glycosaminoglycans and by expression of SOX9 and COL2A1, was also reduced but comparatively better preserved. Crucially, this pattern of a simultaneous, broad suppression of all three mesenchymal lineages argues against the classic idea of a simple lineage shift, in which bone-forming cells are diverted into fat cells. Instead, it points to a deeper loss of overall differentiation competence within the patient-derived progenitors themselves.

The molecular culprit emerged when the researchers examined the Wnt/beta-catenin pathway, the master regulator of mesenchymal lineage commitment. Beta-catenin, the transcriptional co-activator at the heart of canonical Wnt signalling, promotes osteogenesis and chondrogenesis while restraining adipogenesis, and its intracellular abundance is normally kept in check by glycogen synthase kinase-3, which phosphorylates beta-catenin and tags it for proteasomal destruction. In the patient-derived cells, the team found a striking double abnormality. Transcripts for CTNNB1, the gene encoding beta-catenin, were significantly reduced, while GSK3B mRNA was markedly elevated. At the protein level, phosphorylation of GSK3alpha at Tyr279 and GSK3beta at Tyr216, the modifications associated with enhanced enzymatic activity, was substantially increased, reaching roughly 1.8- to 2.2-fold above healthy donor levels in the more severely affected patient line. Total beta-catenin protein and intracellular beta-catenin fluorescence were correspondingly diminished, painting a coherent picture of a kinase pushed into overdrive and a key transcriptional regulator destroyed faster than it should be.

The disease signature extended into inflammation, a domain long suspected to matter in this condition because children with active disease show elevated IL-6 and HMGB1 in synovial fluid. Even without any inflammatory stimulus, the patient-derived mesenchymal cells expressed higher baseline levels of IL6, PTGS2 and CCL2, indicating a primed inflammatory state. When the cells were challenged with IL-1beta, the patient cells responded with larger fold increases in these cytokines than healthy cells, and the Wnt target genes AXIN2 and LEF1, already slightly reduced at baseline, were driven down even further. Western blotting showed that IL-1beta pushed GSK3 phosphorylation higher in patient cells than in controls while beta-catenin, already low, declined still more. These exaggerated responses persisted after osteogenic differentiation, where patient-derived osteoblasts displayed stronger NF-kappaB phosphorylation and greater degradation of its inhibitor I-kappa-B-alpha upon inflammatory stimulation. Transcriptomic sequencing reinforced the theme, revealing enriched alterations in inflammatory signalling, extracellular matrix organization and Wnt-related regulatory pathways in both patient fibroblasts and patient-derived mesenchymal cells, with upregulation of multiple extracellular Wnt antagonists including DKK1, SFRP1, SFRP2, WIF1 and SOST.

The most striking result, and the one with the clearest translational implication, came next. When the researchers treated the patient-derived cells with lithium chloride, a long-established inhibitor of GSK3, beta-catenin fluorescence recovered to levels comparable to untreated healthy donor cells, with the rescue being strongest precisely where the deficit had been greatest. More importantly, the functional defect yielded to the same treatment. Lithium chloride substantially increased mineralized nodule formation and Oil Red O staining in both patient lines during osteogenic and adipogenic induction, and quantitative PCR confirmed that either lithium chloride or the more selective inhibitor CHIR99021 significantly boosted expression of BGLAP, RUNX2, ADIPOQ and PPARG. The differentiation programs had not been deleted; they had merely been silenced by an overactive kinase, and silencing the kinase switched them back on. This established that the mesenchymal failure in Legg-Calvé-Perthes disease reflects a reversible, kinase-dependent signalling imbalance rather than irreversible cellular damage.

The study’s authors are careful to place their findings in context. Observations in patients, such as elevated circulating leptin and increased adipose tissue within the affected femoral head, reflect systemic and tissue-level changes that arise from ischemia, inflammation and altered marrow mechanics, and the in vitro reduction in adipogenesis seen here does not contradict that clinical picture. Rather, the platform isolates the intrinsic cellular component of the disease, complementing animal models in which ischemia was surgically induced in piglets and rodents. Those models have shown that ischemia activates hypoxia-inducible factor 1-alpha and drives inflammatory and angiogenic responses, and the new human data now connect those tissue-level events to a specific, druggable intracellular node inside the progenitors that must rebuild the bone. The authors propose a reciprocal feedback loop in which inflammatory activation sustains GSK3 activity, further destabilizing beta-catenin and progressively compromising skeletal regeneration.

For a disease whose current treatments range from conservative containment to major reconstructive surgery, the prospect of a pharmacological strategy that restores the bone-building capacity of a child’s own progenitor cells is genuinely exciting. Lithium is an old drug with a well-characterized safety profile in other contexts, and the iPSC-based model developed here provides a patient-specific testing ground for optimizing GSK3-targeted regenerative therapies before they reach the clinic. Much work remains, including validating the findings in larger patient cohorts and determining how a GSK3 inhibitor could be delivered safely to the developing femoral head. But the central message stands: the cellular failure underlying a devastating childhood hip disease is not a life sentence written into the genome, but a reversible regulatory state, and with the right key, the machinery of skeletal repair can be switched back on.

Subject of Research: Reversible GSK3/beta-catenin dysregulation in patient-derived iPSC-mesenchymal stem cells from children with Legg-Calvé-Perthes disease

Article Title: Patient‐Derived iPSC‐MSC Modelling Reveals Reversible GSK3‐Mediated Suppression of Mesenchymal Lineage Differentiation in Legg‐Calvé‐Perthes Disease

Article References: Seol, B., Lim, H. J., Song, C. L., Lee, J., & Cho, Y. S. (2026). Patient‐Derived iPSC ‐ MSC Modelling Reveals Reversible GSK3 ‐Mediated Suppression of Mesenchymal Lineage Differentiation in Legg‐Calvé‐Perthes Disease. Journal of Cellular and Molecular Medicine, 30(17), Article e71350. https://doi.org/10.1111/jcmm.71350

Image Credits: AI Generated

DOI: 10.1111/jcmm.71350

Keywords: Legg-Calvé-Perthes disease, induced pluripotent stem cells, mesenchymal stem cells, GSK3, beta-catenin, Wnt signalling, osteonecrosis, osteogenesis, inflammation, lithium chloride, CHIR99021, paediatric orthopaedics

The significance of the finding lies in its dual mechanism. Cardiovascular researchers have traditionally treated endothelial dysfunction and macrophage-driven inflammation as related but distinct strands of the atherosclerosis story. The endothelium, a single-cell-thick lining that governs vascular tone, barrier integrity, and leukocyte trafficking, is often the first casualty of cardiovascular risk factors such as hypertension, hyperlipidemia, and diabetes. When endothelial cells malfunction, they express fewer protective molecules such as nitric oxide and more adhesion molecules that invite circulating monocytes to breach the vessel wall. Meanwhile, once inside the intima, monocytes differentiate into macrophages that gorge on oxidized lipids, transform into foam cells, and release a cascade of inflammatory cytokines that amplify lesion growth. The new work suggests that PLCE1 is a single upstream node that helps orchestrate both of these pathological processes at once.

PLCE1 encodes an enzyme belonging to the phospholipase C family, proteins that cleave the membrane phospholipid PIP2 into two potent second messengers, inositol trisphosphate and diacylglycerol. These messengers mobilize intracellular calcium and activate protein kinase C, triggering a wide range of cellular responses. PLCE1 is unusual among phospholipases because it also carries a Ras-associating domain and a Ras-GEF domain, linking it directly to small GTPase signaling pathways that control cell proliferation, migration, and survival. Genetic studies over the past decade and a half have repeatedly flagged variants within the PLCE1 gene locus in genome-wide association studies of coronary artery disease, and even earlier of stroke risk in some populations. What those association studies could not resolve was whether PLCE1 is merely a bystander genetically linked to true disease drivers, or an active participant in the disease process. The new findings argue firmly for the latter.

Using a combination of cellular models, animal experiments, and mechanistic analyses, the research team demonstrated that elevated PLCE1 activity worsens endothelial dysfunction. In endothelial cells, increased PLCE1 expression was associated with impaired endothelial function markers, disturbed barrier behavior, and a shift toward the pro-inflammatory, pro-adhesive state that characterizes early lesion formation. When the investigators suppressed PLCE1 in experimental models of atherosclerosis, the resulting lesions were less severe, and the endothelial lining displayed healthier functional characteristics. This directional evidence, that manipulation of PLCE1 changes disease severity rather than simply tracking with it, is the kind of causal data that genetic association studies alone can never provide.

The second arm of the mechanism concerns macrophages, the immune workhorses whose transformation into lipid-laden foam cells defines the atherosclerotic plaque. The study found that PLCE1 promotes a pro-inflammatory phenotype in macrophages, driving the production and release of inflammatory mediators that recruit further immune cells and destabilize plaques. Macrophage inflammation is now recognized as a central engine of atherosclerotic progression, a view powerfully validated by the landmark CANTOS clinical trial, which showed that directly targeting the inflammatory cytokine IL-1 beta reduces cardiovascular events independently of cholesterol lowering. By implicating PLCE1 upstream of macrophage inflammatory activation, the new research adds a candidate control point that could, in principle, restrain this inflammatory engine at its source.

The most consequential discovery, however, may be the identification of CTNNB1 as the molecular target linking PLCE1 to both pathologies. CTNNB1 encodes beta-catenin, the central transducer of the canonical Wnt signaling pathway and a transcriptional co-regulator with its finger in countless developmental and inflammatory processes. In the study’s experimental framework, PLCE1 was shown to act on beta-catenin signaling, and beta-catenin in turn mediated the downstream effects on endothelial cells and macrophages. When beta-catenin was experimentally depleted, the harmful consequences of PLCE1 overexpression were blunted. This epistatic relationship, in which removing the target abolishes the effect of the driver, is a classic hallmark of a genuine signaling axis, and it suggests a linear pathway: PLCE1 acts upon beta-catenin, and beta-catenin drives the gene expression programs that produce endothelial dysfunction and macrophage inflammation.

This proposed axis is biologically plausible in light of prior literature. Beta-catenin signaling has been repeatedly implicated in vascular inflammation, with Wnt-beta-catenin activity reported to increase endothelial permeability and to promote inflammatory gene expression in both endothelial cells and macrophages under atherosclerotic conditions. What the new study contributes is the placement of PLCE1 upstream of this pathway in the specific context of arterial disease, transforming scattered mechanistic hints into a coherent, testable model. It also offers a potential explanation for longstanding genetic associations between PLCE1 variants and cardiovascular outcomes: those variants may alter the intensity of beta-catenin signaling in the vessel wall, tuning the inflammatory set point of atherosclerotic tissue.

From a therapeutic standpoint, the findings are provocative but must be tempered by important caveats. Both PLCE1 and beta-catenin are pleiotropic molecules, meaning they perform essential functions far beyond the vascular system. Beta-catenin, in particular, is indispensable for stem cell maintenance in the intestine, bone formation, and a host of developmental processes, which is why systemic Wnt-pathway inhibitors have repeatedly stumbled in cancer trials due to toxicity. Any attempt to translate the PLCE1-beta-catenin axis into a cardiovascular therapy would almost certainly require highly targeted delivery, perhaps to vascular endothelium or lesional macrophages, or the identification of downstream effectors that are more vascular-specific. The study does not itself report a candidate drug or clinical intervention, and its conclusions rest on experimental models whose fidelity to human atherosclerosis, while substantial, is never complete.

Nevertheless, the work exemplifies a broader and encouraging trend in cardiovascular biology: the convergence of human genetics, molecular signaling, and immunology into unified mechanistic accounts of atherosclerosis. For decades, the field’s therapeutic triumphs came almost exclusively from lipid metabolism, embodied by statins and more recently PCSK9 inhibitors. Yet a large residual risk persists in patients whose cholesterol is well controlled, and that residual burden is increasingly attributed to inflammation and vascular dysfunction. Identifying molecules like PLCE1 that couple inflammatory and endothelial pathologies through a defined signaling route gives researchers exactly the kind of targets needed to address this residual risk. It also enriches the interpretation of existing genetic risk scores, which currently aggregate thousands of variants of unknown function. Each variant that is functionally resolved, as PLCE1 variants now partly are, converts statistical prediction into biological insight.

For now, the immediate value of the study lies in its demonstration of a principle: that a single enzyme can coordinate two of the most destructive processes in atherosclerosis through a well-defined molecular partner. Future work will need to confirm the PLCE1-beta-catenin axis in human tissue, map precisely how PLCE1 activity modifies beta-catenin at the molecular level, and determine whether existing or novel pharmacological tools can safely modulate this pathway in patients at risk. If those steps succeed, a gene discovered through population association studies may finally graduate from statistical curiosity to therapeutic target, offering a new angle of attack on the world’s leading cause of death. In a disease as complex and multifactorial as atherosclerosis, every newly charted junction in the signaling map is a potential checkpoint at which progression might be halted, and PLCE1 has just been added to that map in bold.

Subject of Research: The role of PLCE1 in driving atherosclerosis through endothelial dysfunction and macrophage inflammation via CTNNB1

Article Title: PLCE1 exacerbates the development of atherosclerosis by driving endothelial dysfunction and macrophage inflammation via targeting CTNNB1

Article References: Cheng, W.-L., Shi, Y., Zhang, Q., Cai, Z., Jiang, F.-X., Kong, X., Cao, J.-L., Peng, L., Chen, M., He, T., & Wang, H. (2026). PLCE1 exacerbates the development of atherosclerosis by driving endothelial dysfunction and macrophage inflammation via targeting CTNNB1. Cell Death Discovery. https://doi.org/10.1038/s41420-026-03309-2

Image Credits: AI Generated

DOI: 10.1038/s41420-026-03309-2

Keywords: PLCE1, atherosclerosis, CTNNB1, beta-catenin, endothelial dysfunction, macrophage inflammation, cardiovascular disease, Cell Death Discovery, Wnt signaling, foam cells, heart disease, molecular mechanism