Altered Expression of Intestinal Tight Junction Proteins in Heart Failure Patients with Reduced or Preserved Ejection Fraction: A Pathogenetic Mechanism of Intestinal Hyperpermeability
Although intestinal microbiota alterations (dysbiosis) have been described in heart failure (HF) patients, the possible mechanisms of intestinal barrier dysfunction leading to endotoxemia and systemic inflammation are not fully understood. In this study, we investigated the expression of the intesti...
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MDPI AG
2024-01-01
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| author | Eleni-Evangelia Koufou Stelios F. Assimakopoulos Pinelopi Bosgana Anne-Lise de Lastic Ioanna-Maria Grypari Georgia-Andriana Georgopoulou Stefania Antonopoulou Athanasia Mouzaki Helen P. Kourea Konstantinos Thomopoulos Periklis Davlouros |
| author_facet | Eleni-Evangelia Koufou Stelios F. Assimakopoulos Pinelopi Bosgana Anne-Lise de Lastic Ioanna-Maria Grypari Georgia-Andriana Georgopoulou Stefania Antonopoulou Athanasia Mouzaki Helen P. Kourea Konstantinos Thomopoulos Periklis Davlouros |
| author_sort | Eleni-Evangelia Koufou |
| collection | DOAJ |
| description | Although intestinal microbiota alterations (dysbiosis) have been described in heart failure (HF) patients, the possible mechanisms of intestinal barrier dysfunction leading to endotoxemia and systemic inflammation are not fully understood. In this study, we investigated the expression of the intestinal tight junction (TJ) proteins occludin and claudin-1 in patients with HF with reduced (HFrEF) or preserved ejection fraction (HFpEF) and their possible association with systemic endotoxemia and inflammation. Ten healthy controls and twenty-eight patients with HF (HFrEF (n = 14), HFpEF (n = 14)) underwent duodenal biopsy. Histological parameters were recorded, intraepithelial CD3+ T-cells and the expression of occludin and claudin-1 in enterocytes were examined using immunohistochemistry, circulating endotoxin concentrations were determined using ELISA, and concentrations of cytokines were determined using flow cytometry. Patients with HFrEF or HFpEF had significantly higher serum endotoxin concentrations (<i>p</i> < 0.001), a significantly decreased intestinal occludin and claudin-1 expression (in HfrEF <i>p</i> < 0.01 for occludin, <i>p</i> < 0.05 for claudin-1, in HfpEF <i>p</i> < 0.01 occludin and claudin-1), and significantly increased serum concentrations of IL-6, IL-8, and IL-10 (for IL-6 and IL-10, <i>p</i> < 0.05 for HFrEF and <i>p</i> < 0.001 for HFpEF; and for IL-8, <i>p</i> < 0.05 for both groups) compared to controls. Occludin and claudin-1 expression inversely correlated with systemic endotoxemia (<i>p</i> < 0.05 and <i>p</i> < 0.01, respectively). Heart failure, regardless of the type of ejection fraction, results in a significant decrease in enterocytic occludin and claudin-1 expression, which may represent an important cellular mechanism for the intestinal barrier dysfunction causing systemic endotoxemia and inflammatory response. |
| first_indexed | 2024-03-08T09:56:38Z |
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| institution | Directory Open Access Journal |
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| language | English |
| last_indexed | 2024-03-08T09:56:38Z |
| publishDate | 2024-01-01 |
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| spelling | doaj.art-2a31494dffec4238a370497a55a1c54a2024-01-29T13:47:37ZengMDPI AGBiomedicines2227-90592024-01-0112116010.3390/biomedicines12010160Altered Expression of Intestinal Tight Junction Proteins in Heart Failure Patients with Reduced or Preserved Ejection Fraction: A Pathogenetic Mechanism of Intestinal HyperpermeabilityEleni-Evangelia Koufou0Stelios F. Assimakopoulos1Pinelopi Bosgana2Anne-Lise de Lastic3Ioanna-Maria Grypari4Georgia-Andriana Georgopoulou5Stefania Antonopoulou6Athanasia Mouzaki7Helen P. Kourea8Konstantinos Thomopoulos9Periklis Davlouros10Department of Cardiology, Patras University Hospital, 26504 Patras, GreeceDepartment of Internal Medicine and Division of Infectious Diseases, University of Patras Medical School, 26504 Patras, GreeceDepartment of Pathology, Medical School of Patras, 26504 Patras, GreeceLaboratory of Immunohematology, Division of Hematology, Department of Internal Medicine, Medical School, University of Patras, 26504 Patras, GreeceCytology Department, Aretaieion University Hospital, National Kapodistrian University of Athens, 11528 Athens, GreeceDepartment of Nephrology and Transplantation, Patras University Hospital, 26504 Patras, GreeceDepartment of Medicine, University of Patras, 26504 Patras, GreeceLaboratory of Immunohematology, Division of Hematology, Department of Internal Medicine, Medical School, University of Patras, 26504 Patras, GreeceDepartment of Pathology, Medical School of Patras, 26504 Patras, GreeceDivision of Gastroenterology, Department of Internal Medicine, Medical School, University of Patras, University Hospital of Patras, 26504 Patras, GreeceDepartment of Cardiology, Patras University Hospital, 26504 Patras, GreeceAlthough intestinal microbiota alterations (dysbiosis) have been described in heart failure (HF) patients, the possible mechanisms of intestinal barrier dysfunction leading to endotoxemia and systemic inflammation are not fully understood. In this study, we investigated the expression of the intestinal tight junction (TJ) proteins occludin and claudin-1 in patients with HF with reduced (HFrEF) or preserved ejection fraction (HFpEF) and their possible association with systemic endotoxemia and inflammation. Ten healthy controls and twenty-eight patients with HF (HFrEF (n = 14), HFpEF (n = 14)) underwent duodenal biopsy. Histological parameters were recorded, intraepithelial CD3+ T-cells and the expression of occludin and claudin-1 in enterocytes were examined using immunohistochemistry, circulating endotoxin concentrations were determined using ELISA, and concentrations of cytokines were determined using flow cytometry. Patients with HFrEF or HFpEF had significantly higher serum endotoxin concentrations (<i>p</i> < 0.001), a significantly decreased intestinal occludin and claudin-1 expression (in HfrEF <i>p</i> < 0.01 for occludin, <i>p</i> < 0.05 for claudin-1, in HfpEF <i>p</i> < 0.01 occludin and claudin-1), and significantly increased serum concentrations of IL-6, IL-8, and IL-10 (for IL-6 and IL-10, <i>p</i> < 0.05 for HFrEF and <i>p</i> < 0.001 for HFpEF; and for IL-8, <i>p</i> < 0.05 for both groups) compared to controls. Occludin and claudin-1 expression inversely correlated with systemic endotoxemia (<i>p</i> < 0.05 and <i>p</i> < 0.01, respectively). Heart failure, regardless of the type of ejection fraction, results in a significant decrease in enterocytic occludin and claudin-1 expression, which may represent an important cellular mechanism for the intestinal barrier dysfunction causing systemic endotoxemia and inflammatory response.https://www.mdpi.com/2227-9059/12/1/160heart failureintestinal hyperpermeabilitysystemic endotoxemiasystemic inflammationtight junction dysfunction |
| spellingShingle | Eleni-Evangelia Koufou Stelios F. Assimakopoulos Pinelopi Bosgana Anne-Lise de Lastic Ioanna-Maria Grypari Georgia-Andriana Georgopoulou Stefania Antonopoulou Athanasia Mouzaki Helen P. Kourea Konstantinos Thomopoulos Periklis Davlouros Altered Expression of Intestinal Tight Junction Proteins in Heart Failure Patients with Reduced or Preserved Ejection Fraction: A Pathogenetic Mechanism of Intestinal Hyperpermeability Biomedicines heart failure intestinal hyperpermeability systemic endotoxemia systemic inflammation tight junction dysfunction |
| title | Altered Expression of Intestinal Tight Junction Proteins in Heart Failure Patients with Reduced or Preserved Ejection Fraction: A Pathogenetic Mechanism of Intestinal Hyperpermeability |
| title_full | Altered Expression of Intestinal Tight Junction Proteins in Heart Failure Patients with Reduced or Preserved Ejection Fraction: A Pathogenetic Mechanism of Intestinal Hyperpermeability |
| title_fullStr | Altered Expression of Intestinal Tight Junction Proteins in Heart Failure Patients with Reduced or Preserved Ejection Fraction: A Pathogenetic Mechanism of Intestinal Hyperpermeability |
| title_full_unstemmed | Altered Expression of Intestinal Tight Junction Proteins in Heart Failure Patients with Reduced or Preserved Ejection Fraction: A Pathogenetic Mechanism of Intestinal Hyperpermeability |
| title_short | Altered Expression of Intestinal Tight Junction Proteins in Heart Failure Patients with Reduced or Preserved Ejection Fraction: A Pathogenetic Mechanism of Intestinal Hyperpermeability |
| title_sort | altered expression of intestinal tight junction proteins in heart failure patients with reduced or preserved ejection fraction a pathogenetic mechanism of intestinal hyperpermeability |
| topic | heart failure intestinal hyperpermeability systemic endotoxemia systemic inflammation tight junction dysfunction |
| url | https://www.mdpi.com/2227-9059/12/1/160 |
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