TY - JOUR
T1 - FGF21/FGFR1-β-KL cascade in cardiomyocytes modulates angiogenesis and inflammation under metabolic stress
AU - Gare, Sanskruti Ravindra
AU - Ruiz Velasco Hernandez, Andrea
AU - Shen, Jiahan
A2 - Kaur, Namrita
A2 - Miller, Jessica M.
A2 - Abouleisa, Riham
A2 - Ou, Qinghui
A2 - Soran, Handrean
A2 - Mohamed, Tamer
A2 - Liu, Wei
PY - 2023/4/1
Y1 - 2023/4/1
N2 - Diabetes is a metabolic disorder with an increased risk of developing heart failure. Inflammation and damaged vasculature are the cardinal features of diabetes-induced cardiac damage. Moreover, systemic metabolic stress triggers discordant intercellular communication, thus culminating in cardiac dysfunction. Fibroblast growth factor 21 (FGF21) is a pleiotropic hormone transducing cellular signals via fibroblast growth factor receptor 1 (FGFR1) and its co-receptor beta-klotho (β-KL). This study first demonstrated a decreased expression or activity of FGFR1 and β-KL in both human and mouse diabetic hearts. Reinforcing cardiac FGFR1 and β-KL expression can alleviate pro-inflammatory response and endothelial dysfunction upon diabetic stress. Using proteomics, novel cardiomyocyte-derived anti-inflammatory and proangiogenic factors regulated by FGFR1-β-KL signaling were identified. Although not exhaustive, this study provides a unique insight into the protective topology of the cardiac FGFR1-β-KL signaling-mediated intercellular reactions in the heart in response to metabolic stress.
AB - Diabetes is a metabolic disorder with an increased risk of developing heart failure. Inflammation and damaged vasculature are the cardinal features of diabetes-induced cardiac damage. Moreover, systemic metabolic stress triggers discordant intercellular communication, thus culminating in cardiac dysfunction. Fibroblast growth factor 21 (FGF21) is a pleiotropic hormone transducing cellular signals via fibroblast growth factor receptor 1 (FGFR1) and its co-receptor beta-klotho (β-KL). This study first demonstrated a decreased expression or activity of FGFR1 and β-KL in both human and mouse diabetic hearts. Reinforcing cardiac FGFR1 and β-KL expression can alleviate pro-inflammatory response and endothelial dysfunction upon diabetic stress. Using proteomics, novel cardiomyocyte-derived anti-inflammatory and proangiogenic factors regulated by FGFR1-β-KL signaling were identified. Although not exhaustive, this study provides a unique insight into the protective topology of the cardiac FGFR1-β-KL signaling-mediated intercellular reactions in the heart in response to metabolic stress.
KW - Angiogenesis
KW - Diabetic cardiomyopathy
KW - Inflammation
KW - Intercellular communication
KW - Metabolic stress
UR - https://www.scopus.com/pages/publications/85152141156
UR - https://www.mendeley.com/catalogue/267d14f9-c395-3fd1-b2a8-4dca2df45694/
U2 - 10.1016/j.heliyon.2023.e14952
DO - 10.1016/j.heliyon.2023.e14952
M3 - Article
C2 - 37123894
SN - 2405-8440
VL - 9
JO - Heliyon
JF - Heliyon
IS - 4
M1 - e14952
ER -
