Open AccessSynergism between obesity and HFpEF on neutrophils phenotype and its regulation by adipose tissue‐molecules and SGLT2i dapagliflozin
Author(s) -
Almengló Cristina,
Fu Xiaoran,
FloresArias María Teresa,
Fernández Ángel L.,
Viñuela Juan E.,
MartínezCereijo José M.,
Durán Darío,
RodríguezMañero Moisés,
GonzálezJuanatey José R.,
Eiras Sonia
Publication year - 2022
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.17466
Subject(s) - adipose tissue , dapagliflozin , downregulation and upregulation , heart failure with preserved ejection fraction , medicine , endocrinology , integrin alpha m , endothelial dysfunction , cell adhesion molecule , heart failure , chemistry , receptor , ejection fraction , immunology , diabetes mellitus , biochemistry , type 2 diabetes , gene
The adiposity invokes innate immune activity, coronary microvascular dysfunction and consequently heart failure preserved ejection fraction (HFpEF). Our aim was to study the neutrophils profile on obesity and cardiovascular disease and its regulation by adipose tissue‐secretome and dapagliflozin. We have isolated neutrophils from patients undergoing open heart surgery (19 women and 51 men). Its migration activity was performed with culture‐transwell, transcriptional studies of proteolytic enzymes, adhesion molecules or receptors were analysed by real‐time PCR and proteomics (from 20 patients) analysis by TripleTOF mass spectrometer. Differentiated HL‐60 (dHL‐60) was used as a preclinical model on microfluidic for endothelial cells attaching assays and genes regulation with epicardial and subcutaneous fat secretomes from patients (3 women and 9 men) or dapagliflozin 1–10 μM treatments. The transcriptional and proteomics studies have determined higher levels of adhesion molecules in neutrophils from patients with obesity. The adhesion molecule CD11b levels were higher in those patients with the combined obesity and HFpEF factors (1.70 ± 0.06 a.u. without obesity, 1.72 ± 0.04 a.u. obesity or HFpEF without obesity and 1.79 ± 0.08 a.u. obesity and HFpEF; p < .01). While fat‐secretome induces its upregulation, dapagliflozin can modulated it. Because CD11b upregulation is associated with higher neutrophils migration and adhesion into endothelial cells, dapagliflozin might modulate this mechanism on patients with obesity and HFpEF.