Genetics-Informed Mapping Identifies a CRIM1-Associated Endocardial Inflammatory Remodeling State in Acute Myocardial Infarction.
R, R., X, X., Q, L., F, X., L, L., L, S., & Q, Y. (2026). Genetics-Informed Mapping Identifies a CRIM1-Associated Endocardial Inflammatory Remodeling State in Acute Myocardial Infarction.. Medical science monitor : international medical journal of experimental and clinical research. https://doi.org/10.12659/MSM.953619
R R, X X, Q L, F X, L L, L S, et al. Genetics-Informed Mapping Identifies a CRIM1-Associated Endocardial Inflammatory Remodeling State in Acute Myocardial Infarction.. Medical science monitor : international medical journal of experimental and clinical research. 2026; doi: 10.12659/MSM.953619
R R, X X, Q L, et al. Genetics-Informed Mapping Identifies a CRIM1-Associated Endocardial Inflammatory Remodeling State in Acute Myocardial Infarction.[J]. Medical science monitor : international medical journal of experimental and clinical research. 2026. DOI: 10.12659/MSM.953619.
@article{r2026,
author = {Ruan R and Xu X and Liu Q and Xiang F and Luo L and Shi L and Yang Q},
title = {Genetics-Informed Mapping Identifies a CRIM1-Associated Endocardial Inflammatory Remodeling State in Acute Myocardial Infarction.},
journal = {Medical science monitor : international medical journal of experimental and clinical research},
year = {2026},
doi = {10.12659/MSM.953619},
note = {PMID: 42661361},
}
TY - JOUR AU - Ruan R AU - Xu X AU - Liu Q AU - Xiang F AU - Luo L AU - Shi L AU - Yang Q TI - Genetics-Informed Mapping Identifies a CRIM1-Associated Endocardial Inflammatory Remodeling State in Acute Myocardial Infarction. T2 - Medical science monitor : international medical journal of experimental and clinical research PY - 2026 DO - 10.12659/MSM.953619 AN - PMID:42661361 ER -
BACKGROUND Acute myocardial infarction (AMI) reflects inherited susceptibility and inflammatory remodeling, but the cellular contexts linking genetic risk to disease remain unclear. MATERIAL AND METHODS We integrated a meta-transcriptome-wide association study (TWAS) with a human cardiac single-nucleus RNA-sequencing atlas contained 11 individuals (5 AMI and 6 donor) to identify genetics-informed cellular programs. Composite program states were defined by global score quartiles. A fixed 5-gene panel was evaluated for nucleus-level endocardial low-transcriptional-state (Endo_LTS) vs endocardial high-transcriptional-state (Endo_HTS) discrimination within the AMI endocardium using 5-fold leave-1-patient-out cross-validation. Functional follow-up used CRIM1 silencing in hypoxia-treated human induced pluripotent stem cell (hiPSC)-derived endocardial endothelial-like cells and complementary peripheral blood analyses. RESULTS The endocardium exhibited the most prominent infarction-associated increase in TWAS-anchored program activity, with expansion of program-high states and higher CytoTRACE scores. A consensus 5-gene panel (RPS8, PLEC, CFDP1, CRIM1, TNS2) was identified. Among 2163 AMI endocardial nuclei from 5 patients, the state classifier included 364 Endo_LTS and 751 Endo_HTS nuclei; 1048 Endo_MTS nuclei were excluded. Pooled out-of-fold ROC-AUCs ranged from 0.665 to 0.831. The panel also showed discriminatory value in an independent peripheral-blood AMI-vs-control cohort. CRIM1 was prioritized as a candidate linked to the remodeling program. CRIM1 silencing attenuated ACTA2/alpha-SMA, vimentin, LDHA, CCL2, and VEGFA and partially restored CD31, whereas TGF-ß remained elevated. CONCLUSIONS These findings identify a genetics-informed endocardial inflammatory remodeling state in AMI and define a 5-gene surrogate of its activated state. CRIM1 is prioritized as a candidate linked to selected inflammatory, metabolic, and structural outputs. Persistent TGF-b elevation after CRIM1 silencing argues against a simple linear regulatory model and indicates that further mechanistic validation is required.