PhD Scientific Days 2024

Cardiovascular Medicine and Research I.

High FABP4 Plasma Levels, Associated With Low-voltage Area, Increases the Epicardial Fibrosis and Its Glucose Metabolism

Text of the abstract

Introduction. High plasma levels of FABP4 were associated with epicardial fat volume on persistent atrial fibrillation (AF) patients. FABP4 can be released by differentiated adipocytes and macrophages, which may be involved in fibrosis.

Aims. Our aim was to study the association between FABP4 and epicardial fibrosis, which may explain the existence of low-voltage area (LVA) and AF.

Methods. Peripheral FABP4 and galectin-3 levels were analyzed in patients with persistent AF undergoing pulmonary vein isolation (PVI) (n=299) after informed consent. During the intervention, LVA was assessed by invasive electroanatomic voltage mapping (EAM). Epicardial (EAT) and subcutaneous adipose tissue (SAT) (n=6) were obtained from patients undergoing open heart surgery. Stromal cells were isolated by collagenase digestion, cultured and treated with and without FABP4 100ng/ml and/or galectin-3 30ng/ml for 24 hours. The proliferation and migration rates were measured by wound healing assay; mitochondrial activity was studied by MTT assay; and glucose and lactate consumption was detected by colorimetric and fluorescence assays, respectively. Gene expression was assessed by real-time PCR.

Result. Regression analysis determined that the main independent predictors of LVA were age, left atrial area and FABP4 levels. Preclinical "in vitro" studies have shown that FABP4 100ng/mL induced fibrosis in epicardial stromal cells, evidenced by wound healing assay and the increased expression of fibroblast-associated genes. Moreover high FABP4 levels modulates the protein levels and metabolic gene expression on EAT stromal cells and its effect on glucose metabolism without lactate production.

Conclusion. High FABP4 plasma levels are predictors of LVA. Its effect on epicardial fibrosis and glycemic metabolism suggests a possible explanatory mechanism for this association. Although future studies are required, modulation of the effect or production of FABP4 could protect against atrial remodeling and prevent the perpetuation of AF.

Founding. Fondo de Investigaciones Sanitarias (PI19/01330) and co-funded by ISCIII-Subdirección General de Evaluación y Fomento de la Investigación el Fondo Europeo de Desarrollo Regional, Educación e Ordenación Universitaria da Xunta de Galicia (IN607B 2022/04).

xocas.vazquez@rai.usc.es
University of Santiago de Compostela
Supervisor: Sonia Eiras Penas