Altered Expression of Intestinal Tight Junction Proteins in Heart Failure Patients with Reduced or Preserved Ejection Fraction: A Pathogenetic Mechanism of Intestinal Hyperpermeability
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
Affiliations
Eleni-Evangelia Koufou
Department of Cardiology, Patras University Hospital, 26504 Patras, Greece
Stelios F. Assimakopoulos
Department of Internal Medicine and Division of Infectious Diseases, University of Patras Medical School, 26504 Patras, Greece
Pinelopi Bosgana
Department of Pathology, Medical School of Patras, 26504 Patras, Greece
Anne-Lise de Lastic
Laboratory of Immunohematology, Division of Hematology, Department of Internal Medicine, Medical School, University of Patras, 26504 Patras, Greece
Ioanna-Maria Grypari
Cytology Department, Aretaieion University Hospital, National Kapodistrian University of Athens, 11528 Athens, Greece
Georgia-Andriana Georgopoulou
Department of Nephrology and Transplantation, Patras University Hospital, 26504 Patras, Greece
Stefania Antonopoulou
Department of Medicine, University of Patras, 26504 Patras, Greece
Athanasia Mouzaki
Laboratory of Immunohematology, Division of Hematology, Department of Internal Medicine, Medical School, University of Patras, 26504 Patras, Greece
Helen P. Kourea
Department of Pathology, Medical School of Patras, 26504 Patras, Greece
Konstantinos Thomopoulos
Division of Gastroenterology, Department of Internal Medicine, Medical School, University of Patras, University Hospital of Patras, 26504 Patras, Greece
Periklis Davlouros
Department of Cardiology, Patras University Hospital, 26504 Patras, Greece
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 (p p p p p p p p p < 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.
