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  • LDL‑induced NLRC3 inflammasome activation in cardiac fibroblasts contributes to cardiomyocytic dysfunction.

LDL‑induced NLRC3 inflammasome activation in cardiac fibroblasts contributes to cardiomyocytic dysfunction.

Molecular medicine reports (2021-05-27)
Peng Wang, Wenbo Zhang, Zhen Feng, Jian Zhang, Ying Sun, Wei Zhang
ABSTRACT

Heart failure (HF) is a progressive myocardial disease that affects pulse rate. Notably, chronic inflammation serves a crucial role in cardiac dysfunction and HF. Appropriate cardiomyocyte‑fibroblast communication is essential for cardiac function. In addition, cardiac fibroblasts (CFs) are the main cellular population in the cardiac microenvironment; therefore, determining the role of CFs in HF progression and the associated molecular basis is important. In the present study, ELISAs were performed to detect inflammatory factors in the sera of patients with HF and their association with CF activation was analyzed using Pearson's correlation coefficient. The mechanism underlying the proinflammatory phenotype of CFs was investigated via western blotting. Notably, the levels of IL10 and TNF‑α were significantly increased in the sera of patients with HF. Further analysis revealed that CFs were extensively activated in the cardiac tissues of patients with HF and released excessive amounts of cytokines, which could impair the viability of cardiomyocytes. Moreover, low‑density lipoprotein (LDL)‑induced NLRC3 inflammasome was activated in CFs, which gave rise to proinflammatory phenotypes. Targeting LDL in CFs significantly improved the functioning of cardiomyocytes and inhibited apoptosis. These findings highlighted the critical role of LDL in inflammasome activation; to the best of our knowledge, the present study is the first to reveal that CF‑induced microenvironmental inflammation may suppress cardiomyocyte viability. The present study established the cellular basis for CF activation during HF progression and provided information on the cellular interactions important for HF treatment.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-Mouse IgG (whole molecule)–Peroxidase antibody produced in rabbit, IgG fraction of antiserum, buffered aqueous solution
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Mouse IL-1 β ELISA Kit, for cell and tissue lysates
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Human IL-10 ELISA Kit
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Human IL-18 BPa  ELISA Kit, for serum, plasma, cell culture supernatant and urine