Aldosterone remodels human endothelium

Area of Science:

• Endocrinology
• Cell Biology
• Biophysics

Background:

• Aldosterone induces endothelial cell swelling and stiffening.
• The precise mechanisms behind these aldosterone-induced cellular changes remain unclear.
• Amiloride-sensitive sodium and water transport are implicated but not fully understood.

Purpose of the Study:

• To investigate whether intracellular water or organic matter accumulation drives aldosterone-induced endothelial cell alterations.
• To elucidate the underlying mechanisms of endothelial cell structural and functional changes in response to aldosterone.

Main Methods:

• Utilized atomic force microscopy (AFM) for imaging and mechanical nanosensing of endothelial cells.
• Quantified single-cell water content, organic matter, and intracellular pressure in human umbilical vein endothelial cells (HUVEC).
• Assessed the physical robustness of aldosterone-treated endothelium to blood flow using an in vitro perfusion chamber.

Main Results:

• Aldosterone treatment led to a decrease in HUVEC water content (82% to 71%) and a significant increase in organic matter (18% to 29%).
• Intracellular cell pressure rose by 114% in aldosterone-treated HUVEC.
• Aldosterone-treated endothelium exhibited gaps between cells after blood perfusion, indicating vulnerability to shear stress.
• Mineralocorticoid receptor antagonists (spironolactone, eplerenone) successfully blocked aldosterone's effects.

Conclusions:

• Aldosteronism promotes intracellular organic matter accumulation at the expense of cell water, leading to endothelial stiffening.
• The stiffened endothelium becomes vulnerable to shear stress, potentially explaining vascular damage in conditions like hypertension with high aldosterone.
• These findings provide a mechanistic link between aldosterone levels and endothelial dysfunction.