Exosomes in ultrastructural resistance artery remodeling of human hypertension.

Abstract

We previously reported that human hypertension is associated with ultrastructural remodeling of systemic resistance arteries. Endothelial and smooth muscle cells (SMC) displayed mitochondrial and sarco-endoplasmic reticulum stress, accompanied by SMC migration toward the intima. Exosomes, nano-sized phospholipid bilayer-enclosed vesicles released from cells upon fusion of multivesicular bodies (MVB) with the plasma membrane, are thought to be involved in the endothelial-to-SMC communication regulating these adaptations. However, there is a dearth of ultrastructural studies on microvascular exosomes during hypertension. Therefore, we characterized and quantified exosomes in omental resistance-sized arteries (200-400 μm), obtained during surgery in 19 women (9 hypertensive), mean age 42 y (SE 1). The number of MVBs was around 7-fold higher in hypertensives, mean, 3.8 (SE 0.2)/cell vs 0.5 (0.1) in normotensives, with a shift from a scant dispersion of intracellular MVBs in normotensives, toward a prominent abluminal endothelial location in hypertensives. MVBs also contained significantly more exosomes in hypertensives, mean 7.9 (0.2) vs 5.0 (0.2)/MVB in normotensives.