beta-hydroxybutyrate induces acute pulmonary endothelial dysfunction in rabbits

Area of Science:

• Physiology
• Endothelial Cell Biology
• Metabolic Research

Background:

• Endothelial cells (EC) play a crucial role in vascular homeostasis.
• Ketone bodies and glucose are key metabolic fuels with potential effects on EC function.
• Understanding the impact of varying metabolic states on pulmonary ECs is vital for respiratory health.

Purpose of the Study:

• To investigate the effects of high concentrations of beta-hydroxybutyrate (beta OHB) and glucose on endothelial cell (EC) function in perfused rabbit lungs.
• To compare the impact of beta OHB, acetoacetate (AcAc), and glucose on pulmonary vascular integrity and EC activity.

Main Methods:

• Perfused rabbit lungs were exposed to different concentrations of beta OHB, AcAc, and glucose.
• Endothelial angiotensin-converting enzyme (eACE) activity was measured.
• Lung tissue was assessed for dry to wet weight ratios.
• Histological examination was performed to evaluate neutrophil infiltration and tissue damage.

Main Results:

• A high concentration of beta-hydroxybutyrate (5 mM) significantly decreased eACE activity and lung dry to wet weight ratios.
• The same concentration of beta OHB induced massive hemorrhage and neutrophil infiltration in lung tissue.
• Lower concentrations of beta OHB (1 mM), acetoacetate (10 mM), or high glucose (25 mM) did not elicit significant adverse effects on EC function or lung tissue.

Conclusions:

• Acute perfusion with high beta-hydroxybutyrate concentrations leads to pulmonary endothelial cell dysfunction in rabbit lungs.
• Beta-hydroxybutyrate, but not acetoacetate or glucose, causes significant vascular damage and inflammatory responses.
• These findings highlight the specific detrimental effects of elevated beta OHB on pulmonary endothelial integrity.