Purpose <p>Inflammation is a key contributor to the pathogenesis and progression of heart failure (HF), correlating with increased morbidity and mortality. This study aimed to evaluate the molecular impact of a 24-week nutritional intervention on inflammasome-related components in HF patients, comparing a Mediterranean diet alone versus the same diet supplemented with hypercaloric, high-protein oral nutritional supplements (ONS) enriched with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). In a cohort of 38 patients, expression levels of inflammasome markers were assessed via microfluidic quantitative polymerase chain reaction (PCR) in peripheral blood mononuclear cells at baseline and post-intervention.</p> Results <p>Some components, especially cytokines and apoptosis regulation components are overexpressed in patients with sarcopenia (NLRP1, NLRC4, CASP1, CASP5, CTSL, IFI16, TLR8, PSXR7, CCR1, CHUCK, MAPK14, CDKN1B). We observed a significant downregulation of Nod-like receptors NLRP12 and NLRP6, along with decreased expression of inflammasome activation components CASP5, TLR2, and TLR9 in the intervention group (<i>p</i> &lt; 0.05). Additionally, cytokines and inflammation-related molecules such as CXCR1, CXCR2, TGFB, CCL2, and NF-κB showed reduced expression, while the inhibitor CHUCK increased (<i>p</i> &lt; 0.05). Cell cycle regulators also shifted, with decreased CDKN2D expression (<i>p</i> &lt; 0.05), suggesting potential effects on cellular senescence and DNA repair pathways. Notably, these molecular changes were absent in patients adhering solely to the Mediterranean diet.</p> Conclusions <p>these findings suggest that supplementing a Mediterranean diet with hypercaloric, high-protein, EPA and DHA-enriched ONS induces molecular modifications in inflammasome pathways associated with cardiac remodeling. Therefore, targeted nutritional strategies may offer a promising adjunct to improve cardiac function and disease progression in HF patients.</p>

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Modulation of inflammasome components in patients with heart failure using oral nutritional supplements: investigating the molecular mechanisms beyond the clinical benefit

  • Aura D. Herrera-Martínez,
  • Natalia Hermán-Sánchez,
  • Miguel E. G-García,
  • Concepción Muñoz-Jiménez,
  • Jesús M. Pérez-Gómez,
  • Antonio J. Montero-Hidalgo,
  • José López-Aguilera,
  • Rafael González-Manzanares,
  • María Ángeles Gálvez-Moreno,
  • María José Molina-Puerta,
  • Raúl M. Luque

摘要

Purpose

Inflammation is a key contributor to the pathogenesis and progression of heart failure (HF), correlating with increased morbidity and mortality. This study aimed to evaluate the molecular impact of a 24-week nutritional intervention on inflammasome-related components in HF patients, comparing a Mediterranean diet alone versus the same diet supplemented with hypercaloric, high-protein oral nutritional supplements (ONS) enriched with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). In a cohort of 38 patients, expression levels of inflammasome markers were assessed via microfluidic quantitative polymerase chain reaction (PCR) in peripheral blood mononuclear cells at baseline and post-intervention.

Results

Some components, especially cytokines and apoptosis regulation components are overexpressed in patients with sarcopenia (NLRP1, NLRC4, CASP1, CASP5, CTSL, IFI16, TLR8, PSXR7, CCR1, CHUCK, MAPK14, CDKN1B). We observed a significant downregulation of Nod-like receptors NLRP12 and NLRP6, along with decreased expression of inflammasome activation components CASP5, TLR2, and TLR9 in the intervention group (p < 0.05). Additionally, cytokines and inflammation-related molecules such as CXCR1, CXCR2, TGFB, CCL2, and NF-κB showed reduced expression, while the inhibitor CHUCK increased (p < 0.05). Cell cycle regulators also shifted, with decreased CDKN2D expression (p < 0.05), suggesting potential effects on cellular senescence and DNA repair pathways. Notably, these molecular changes were absent in patients adhering solely to the Mediterranean diet.

Conclusions

these findings suggest that supplementing a Mediterranean diet with hypercaloric, high-protein, EPA and DHA-enriched ONS induces molecular modifications in inflammasome pathways associated with cardiac remodeling. Therefore, targeted nutritional strategies may offer a promising adjunct to improve cardiac function and disease progression in HF patients.