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Role of Endothelial Cell Specific Adhesion Molecule in the Development of Pulmonary Microvascular Dysfunction in HFpEF
Author(s) -
Buncha Vadym,
Fopiano Katie Anne,
Tian Yanna,
Bagi Zsolt
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2021.35.s1.03714
Subject(s) - heart failure with preserved ejection fraction , cardiology , medicine , ventricle , vascular resistance , diastole , heart failure , pulmonary artery , pulmonary edema , lung , pulmonary hypertension , endothelial dysfunction , ejection fraction , hemodynamics , blood pressure
Pulmonary complications are common in patients with heart failure with preserved ejection fraction (HFpEF), but the nature of pathomechanisms is poorly understood. The uninephrectomized and aldosterone infused (UNX‐aldo) mice was employed to test the hypothesis that pulmonary microvascular dysfunction develops in HFpEF. Using echocardiography, we found that 4 weeks after UNX‐aldo procedure mice exhibit increased left ventricle (LV) mass and reduced E/A ratio (E=early, A=late mitral inflow peak velocities) and increased DT (E wave deceleration time,) with no change in ejection fraction, similar to that of seen in human HFpEF. The UNX‐Aldo mice had increased lung weight and wet to dry ratios, and displayed an increased pulmonary vascular resistance, when assessed in isolated perfused lungs. UNX‐Aldo mice also had a reduced luminal diameter and increased wall thickness, when measured in isolated and pressurized small pulmonary arteries. Along with these pulmonary vascular changes we found that the serum level and protein expression of endothelial cell specific adhesion molecule (ESAM) in pulmonary arteries were significantly elevated in UNX‐Aldo mice. Mice with genetic deletion of ESAM were protected against the development of LV diastolic dysfunction and displayed reduced pulmonary edema formation and pulmonary vascular resistance. Collectively, these results indicate a novel pathological role for ESAM in the development of pulmonary microvascular dysfunction in HFpEF.