Accumulation of intimal vascular smooth muscle cells is a trait of atherosclerosis.
Endothelial cells lining vascular luminal surface represent an important site of signalling
and development of damage induced by reactive oxygen species (ROS) during
ischemia, inflammation and other pathological conditions. Targeted delivery of ROS
modulating enzymes conjugated with antibodies to endothelial surface molecules
provides site-specific interventions leading to endothelial damage. Excessive ROS
production causes pathological activation of endothelium including exposure of cell
adhesion molecules.
The intercellular adhesion molecule-1 (ICAM-1) is a member of the immunoglobulin
(Ig) superfamily which is present on the surface of several other cell types, including
endothelial cells. Adhesion molecules [e.g., ICAM-1, vascular cell adhesion molecule
1 (VCAM-1) and platelet-endothelial cell adhesion molecule-1 (PECAM-1)] if in
contact with an activated endothelium could represent attractive targets for delivery
of drugs and imaging probes to vascular pathological sites.
The present study was designed to investigate, with immunochemical and immunohistochemical
techniques, the effect of treatment with thioctic acid enantiomers
on heart and kidney endothelium in spontaneously hypertensive rats (SHR) used as
a model of hypertensive end organ damage. Normotensive Wistar-Kyoto rats were
used as a reference group. Arterial hypertension was accompanied by an increased
oxidative stress status in the kidney and heart. ICAM, VCAM and PECAM expression
was significantly greater in the renal endothelium of SHR. In the heart VCAM
expression was higher than ICAM and PECAM and increased in SHR. (+/-)-Thioctic
acid and (+)-thioctic acid treatment prevented adhesion molecules expression in renal
and cardiac vascular endothelium.
Based on these data, it is possible to conclude that endothelial molecules investigated
can be used for studying vascular injury on target organs of hypertension. The
effects observed after treatment with thioctic acid could open new perspectives for
countering heart and kidney microvascular injury, quite common in several diseases
affecting these organs
