Dataset Information

Therapeutic CD14 heart proteome

ABSTRACT: Therapeutic remodelling and repair of murine heart induced by CD14 antibody treatment. Global (apex) heart and macrophage-derived (FACS) proteome remodelling of CD14 antibody-based therapeutic.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Heart, Macrophage

DISEASE(S): Myocardial Ischemia

SUBMITTER: david greening

LAB HEAD: David Greening

PROVIDER: PXD041192 | Pride | 2026-01-19

REPOSITORIES: Pride

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Publications

CD14 Blockade Modulates Macrophage-Mediated Immunological Injury in a Translational Model of Reperfused ST-Segment Elevation Myocardial Infarction.

D'Elia Nee Brown Aascha A AA Kiriazis Helen H Bloom Jason J Noonan Jonathan J Hsu Ian I Farrugia Gabriella E GE Fang Haoyun H Jansen Stephanie S Carvajal Natalia N Krstevski Crisdion C Shihata Waled A WA Tham Yow Keat YK Vais Angela A Cohen Camilla C Parslow Adam C AC Johnson Chad C Thomas Anita C AC Dona Malathi S I MSI Grigolon Kyah K Loh Scott J Y SJY Krippner Guy G Wright David K DK Wang Bing H BH Abbate Antonio A Amrute Junedh J Lavine Kory K Appleby Mark W MW Crowe David D Redlich Garry G Ziegelaar Brian W BW McMullen Julie R JR Greening David W DW Pinto Alexander R AR Kaye David M DM Donner Daniel G DG

JACC. Basic to translational science 20251023 11

These preclinical trials provide the first evidence of cluster of differentiation 14 (CD14) blockade with a murine analogue of atibuclimab, a CD14-neutralizing antibody, preventing secondary immunological exacerbation of cardiac injury in a translational mouse model of reperfused ST-segment elevation myocardial infarction (STEMI), assessed using multiple clinical modalities. Multiomic studies suggest CD14 blockade downregulated macrophage-specific proinflammatory and tissue-wide remodeling proce ...[more]

PMID: 41134248

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Project description:Objectives: To test whether (1) electromechanical dyssynchrony induces region-specific alterations in the myocardial transcriptome and (2) dyssynchrony-induced gene expression changes can be corrected by cardiac resynchronization (CRT). Background: To date, CRT is the only heart failure treatment that can both acutely and chronically increase systolic function and prolong survival, something not yet achieved by a drug therapy. However, the mechanisms underlying the benefits of CRT remain elusive. Methods: Adult dogs underwent left bundle branch ablation (LBBB) and right atrial pacing at 200 bpm for either 6 weeks (dyssynchronous heart failure, DHF, n=12) or 3 weeks followed by 3 weeks of resynchronization by bi-ventricular pacing at the same pacing rate (CRT, n=10). Control animals without LBBB were not paced (NF, n=14). Echocardiography and invasive hemodynamic measurements were performed at 3 and 6 weeks. At 6 weeks, RNA was isolated from the anterior and lateral LV walls and hybridized onto canine-specific 44K microarrays. Results: In DHF, transcriptional changes consistent with re-expression of a fetal gene program were primarily observed in the anterior LV, resulting in increased regional heterogeneity of gene expression within the left ventricle. Dyssynchrony-induced region-specific expression changes in 1050 transcripts were reversed by CRT to levels of NF hearts (false discovery rate <5%). CRT remodeled transcripts with metabolic and cell signaling function and greatly reduced regional heterogeneity of gene expression compared with DHF. Conclusions: Our results demonstrate a profound effect of electromechanical dyssynchrony on the regional cardiac transcriptome, causing gene expression changes primarily in the anterior LV wall. CRT corrected the alterations in gene expression in the anterior wall by reversing the fetal gene expression pattern, supporting a global effect of biventricular pacing on the ventricular transcriptome that extends beyond the pacing site in the lateral wall. Designed as a 1-color experiments, samples from anterior and lateral left ventricular myocardium from non-failing, DHF and CRT animals were labeled with Cy3 and hybridized onto Agilent 44K long oligonucleotide arrays.

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Dataset Information

Therapeutic CD14 heart proteome

Dataset's files

Publications

CD14 Blockade Modulates Macrophage-Mediated Immunological Injury in a Translational Model of Reperfused ST-Segment Elevation Myocardial Infarction.

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