Key result
Transcriptomic analysis reveals endothelial and fibroblast activation in HF, with higher CCL3/CCL4-CCR5-driven inflammation in ICM.
Why the study?
Owing to high mortality rates and the elusive pathogenesis of heart failure, a thorough identification of genetic factors was needed to provide novel insights into its molecular basis.
Observational (n=79)
Integrative transcriptomic analysis identifies distinct cellular and molecular mechanisms, particularly heightened inflammation and immune activity, differentiating ischemic from dilated cardiomyopathy.
Hypothesis-generating for CCR5-targeted therapies in ischemic cardiomyopathy; prospective validation required before clinical consideration.
Owing to the high mortality rates of heart failure (HF), a more detailed description of the HF becomes extremely urgent. Since the pathogenesis of HF remain elusive, a thorough identification of the genetic factors will provide novel insights into the molecular basis of this cardiac dysfunction. In our research, we performed publicly available transcriptome profiling datasets, including non-failure (NF), dilated cardiomyopathy (DCM) and ischemic cardiomyopathy (ICM) hearts tissues. Through principal component analysis (PCA), gene differential expression analysis, gene set enrichment analysis (GSEA), and gene Set Variation Analysis (GSVA), we figured out the candidate genes noticeably altered in HF, the specific biomarkers of endothelial cell (EC) and cardiac fibrosis, then validated the differences of the inflammation-related cell adhesion molecules (CAMs), extracellular matrix (ECM) genes, and immune responses. Taken together, our results suggested the EC and fibroblast could be activated in response to HF. DCM and ICM had both commonality and specificity in the pathogenesis of HF. Higher inflammation in ICM might related to autocrine CCL3/CCL4-CCR5 interaction induced chemokine signaling activation. Furthermore, the activities of neutrophil and macrophage were higher in ICM than DCM. These findings identified features of the landscape of previously underestimated cellular, transcriptomic heterogeneity between ICM and DCM.
No takes yet. Share an insight, caveat, or question.
A 2022 study conducted an observational in Heart Failure (n=79). Heart failure (Dilated and Ischemic Cardiomyopathy) vs. Non-failure (NF) controls was evaluated on Differential gene expression and cell type specific marker enrichment. Integrative transcriptomic analysis revealed that endothelial cells and fibroblasts are activated in heart failure, with ischemic cardiomyopathy showing higher inflammation driven by CCL3/CCL4-CCR5 signaling.