Mice with endothelial cell-selective adhesion molecule deficiency develop coronary microvascular rarefaction and left...

Area of Science:

• Cardiovascular Biology
• Endothelial Cell Biology
• Molecular Cardiology

Background:

• Endothelial cell-selective adhesion molecule (ESAM) is known to regulate inflammatory cell interactions and angiogenesis.
• Its specific role in cardiac vascularization and diastolic function under physiological and pathological conditions remains largely unexplored.

Purpose of the Study:

• To investigate the function of ESAM in cardiac vascularization, inflammatory cell infiltration, and left ventricle (LV) diastolic function.
• To determine the impact of ESAM deficiency on cardiac health during basal and hemodynamic stress.

Main Methods:

• Utilized ESAM-deficient (ESAM-/-) mice and wild-type littermates.
• Induced cardiac stress using uninephrectomy and aldosterone infusion (UNX-Aldo).
• Assessed cardiac function via echocardiography, coronary vascular density through 3D reconstruction, and inflammatory markers (cytokines, neutrophils).

Main Results:

• ESAM-/- mice exhibited normal systolic function but developed significant LV diastolic dysfunction.
• Reduced coronary vascular density and impaired endothelial sprouting were observed in ESAM-/- mice.
• ESAM deficiency exacerbated LV diastolic dysfunction and pulmonary edema under UNX-Aldo-induced stress.
• Elevated myocardial inflammation and neutrophil infiltration were noted in ESAM-/- mice.

Conclusions:

• ESAM is essential for maintaining proper myocardial vascularization and LV diastolic function.
• ESAM plays a protective role against cardiac dysfunction during hemodynamic overload.
• Targeting ESAM may offer therapeutic potential for diastolic heart failure.