Arterioscler Thromb Vasc Biol. 2026 Apr 2. doi: 10.1161/ATVBAHA.125.324171. Online ahead of print.

ABSTRACT

BACKGROUND: Joint use of multiple molecular layers can be useful to prioritize targets for mechanistic studies. Application of coronary disease in large populations is an emerging field.

METHODS: We used reported circulating proteomic data (Somascan aptamer-based) from ≈3000 individuals in the CARDIA study (Coronary Artery Risk Development in Young Adults), measuring association with prevalent and 10-year incident coronary artery calcium (CAC) score. We used a multiparametric approach to prioritize circulating protein-CAC associations via genomics of circulating protein levels and coronary artery transcription.

RESULTS: Proteins linked to prevalent/incident CAC in CARDIA implicated pathogenic mechanisms of vascular disease, including fibrosis and inflammation (GDF-15 [growth/differentiation factor 15], CDCP1 [CUB domain-containing protein 1], GSN [gelsolin], THBS2 [thrombospondin-2], chemokines, RNAS6), oxidative lipid metabolism (CILP2), extracellular matrix remodeling and signaling (MMPs [matrix metalloproteinases], TIMP-1, integrins), calcification (Notch 1, ARHGAP36 [Rho GTPase-activating protein 36]), and metabolism (GIP [gastric inhibitory polypeptide]), as well as new proteins not previously reported. Using protein-wide association study genetic approaches, several targets with nominal evidence in CAC proteomics were associated with atherosclerosis or myocardial infarction in over 300K individuals, including PCSK9 (proprotein convertase subtilisin/kexin type 9) and APO C₁. Finally, the coronary artery-specific transcriptome-wide association study of CAC yielded genes with previously implicated mechanistic roles in vascular homeostasis, inflammation, and metabolism, as well as genes without previously described function in CAC. Overlap across CAC proteomics and transcriptome-wide association study highlighted genes involved in vascular inflammation (S100A9), cardiac development (HES1), vessel wall structure (SPARCL1), and vascular dysfunction or plaque (NOTCH3, TNFSF12, S100A12).

CONCLUSIONS: These results report population-level multiomics in human coronary calcification, presenting a method to identify disease-relevant targets through integration of human genetic approaches with multiomics.

PMID:41924874 | DOI:10.1161/ATVBAHA.125.324171

Aging Dis. 2026 Mar 19. doi: 10.14336/AD.2025.1571. Online ahead of print.

ABSTRACT

Gastric cancer (GC) remains a leading cause of cancer-related morbidity and mortality worldwide, with poor prognosis for advanced-stage patients. Therefore, in-depth exploration of the mechanisms underlying GC initiation and progression, as well as the development of novel therapeutic strategies, is of crucial importance. Cellular senescence is a stable cell cycle arrest program that plays a dual role in GC. It exerts tumor-suppressive effects via growth arrest but also promotes tumor progression and immune evasion by remodeling the tumor microenvironment (TME) through senescence-associated secretory phenotype (SASP). This review comprehensively elucidates the molecular mechanisms of cellular senescence in GC and the core regulatory networks involving gene regulation, epigenetic modifications, metabolic reprogramming, and cell cycle arrest. Additionally, the review highlights how senescent cells foster an immunosuppressive microenvironment via SASP, forming a self-reinforcing feed-forward loop. Regarding therapeutic strategies, we summarize potential approaches targeting cellular senescence, including senescence induction, senescent cell clearance, SASP modulation, and multi-target synergistic therapy by integrating epigenetic regulation, metabolic intervention, and immune microenvironment modulation. Despite progress, numerous challenges remain. Future studies should leverage multi-omics technologies, novel models' development, and large-scale clinical trials to advance the clinical translation of GC cellular senescence research, providing new insights for improving prognosis.

PMID:41910653 | DOI:10.14336/AD.2025.1571