Systemic Loss of FKBPL Uncovers Diabetes-Dependent Pathways of Myocardial and Vascular Injury

BACKGROUND: Impaired angiogenesis underpins cardiovascular disease, particularly in people with diabetes; however, molecular mechanisms are still poorly understood. This study aims to decipher the role of an emerging antiangiogenic protein, FKBPL (FK506-binding protein–like), on cardiac structure and function, vascular integrity, and inflammatory signaling in in vivo and in vitro models of diabetes. METHODS: In vivo, FKBPL transgenic mice ( fkbpl +/− ) were used to examine the metabolic and cardiovascular function and FKBPL-mediated mechanisms in streptozotocin-induced diabetes. In addition, comprehensive in vitro assessments of endothelial function and mechanisms were performed in normal/high-glucose and high/low-FKBPL conditions. RESULTS: Fkbpl +/− mice show signs of early cardiac remodeling (increased E/A [early-to-atrial filling velocity ratio] ratio, P =0.047, and cardiomyocytes size, P =0.0018; reduced collagen deposition, P =0.013; col1a1 mRNA reduction, P =0.0028) and aberrant expression of cardiac vascular dysfunction proteins (ICAM-1 [intercellular adhesion molecule 1], P