FGFR1/KLB-MFG-E8 Maintains Microvascular Integrity and Adaptive Cardiac Remodeling.

Cardiomyocyte FGFR1/KLB signaling is linked to preserved myocardial capillary density in diabetic mice, and loss of either receptor leads to decompensated remodeling.

• Why it matters: Diabetes-associated endothelial defects impair cardiac remodeling and function, but the cardiomyocyte-to-endothelial communication that protects microvasculature is not well defined.
• What they did: Type 2 diabetes was induced in male and female mice with a high-fat, high-sucrose diet plus low-dose streptozotocin; cardiomyocyte FGFR1 or KLB was deleted using α-MHC-Cre, and mechanisms were tested with multiomics, reporter assays, and endothelial angiogenesis readouts.
• The result: CEBPβ regulated cardiomyocyte MFG-E8, which increased endothelial viability and branching; restoring FGFR1 and KLB together rescued capillary rarefaction, and genetic or pharmacologic MFG-E8 enhancement reversed capillary loss and improved cardiac function, with stronger effects in males.

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