LRRC10 is required to maintain cardiac function in response to pressure overload

Area of Science:

• Cardiology
• Molecular Biology
• Physiology

Background:

• The cardiomyocyte-specific leucine-rich repeat containing protein (LRRC)10 has known critical functions in the mammalian heart.
• The role of LRRC10 in the heart's response to biomechanical stress was previously undetermined.

Purpose of the Study:

• To investigate the function of LRRC10 in the heart's response to biomechanical stress.
• To determine the impact of LRRC10 absence on cardiac structure and function under pressure overload.

Main Methods:

• Transverse aortic constriction was performed on Lrrc10-null (Lrrc10(-/-)) mice and control mice.
• Cardiac function, ventricular dimensions, heart weight, and cardiomyocyte contractility were assessed.
• LRRC10's interaction with actin and the effect of pressure overload on this interaction were examined.

Main Results:

• Lrrc10(-/-) mice exhibited severe cardiac dysfunction, ventricular dilation, and increased heart weight under mild pressure overload compared to controls.
• Absence of LRRC10 led to greater cardiac hypertrophy and structural remodeling, but not increased fibrosis or myocyte dropout.
• Lrrc10(-/-) cardiomyocytes showed reduced contractility, and the LRRC10-actin interaction was diminished after pressure overload.

Conclusions:

• LRRC10 is essential for maintaining cardiac performance and structural integrity under biomechanical stress.
• The interaction between LRRC10 and actin is critical for the heart's response to mechanical stress.
• Dysregulation or mutation of LRRC10 may increase susceptibility to severe cardiac disease in humans.