Morphology of cardiac and renal microvasculature in spontaneously hypertensive rat. Activity of thioctic acid

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

Effects of stereoisomers of thioctic acid on rat renal vasculature microanatomy

Metabolism of oxygen by cells can generate potentially dangerous reactive oxygen species (ROS). Endothelial cells lining vascular luminal surface are an important site of signalling molecules and a ROS target during ischemia, inflammation and other pathological conditions. Targeted delivery of ROS modulating enzymes conjugated with antibodies to endothelial surface molecules provide site-specific interventions of endothelial ROS. Excessive ROS cause pathological activation of endothelium including exposure to cell adhesion molecules. Intercellular adhesion molecule-1 (ICAM-1) is a member of the Ig superfamily and is also found on the surface of several other cell types, including endothelial cells. These molecules [e.g., ICAM-1, vascular cell adhesion molecule 1 (VCAM-1) and platelet-endothelial cell adhesion molecule-1 (PECAM-1)] exposed on activated endothelium represent attractive targets for delivery of drugs and imaging probes to pathological sites in the vasculature. This study has investigated the effect of different stereoisomers of the antioxidant thioctic acid on the endothelium of rat kidney vasculature. Twenty-week-old spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats were treated for 2 weeks with a daily dose of 12.5 nM/kg racemic (+/-)-, (+)- or (-)-thioctic acid. Kidney vascular microanatomy was Investigated by ICAM-1, VCAM-1 and PECAM-1 immunochemistry and immunohistochemistry. . Treatment with thioctic acid significantly improved renal vascular endothelium status by preventing the ICAM and VCAM adhesion. (+)-Thioctic acid elicited the most sustained effect, (+/-)-thioctic acid was less effective and (-)-thioctic acid worsened activity of the compound. The above data suggest that (+)-thioctic acid, the naturally-occurring enantiomer of the compound, is probably the only form of it able to interfere with endothelial adhesion mechanisms in renal vasculature. The comparatively lower activity of racemic (+/-)- thioctic acid is likely determined by the negative impact of (-)-thioctic acid on the parameters under investigation. Analysis of vascular intercellular adhesion mechanisms could represent an interesting approach for investigating specific vascular disorders and also other pathologies in which vascular involvement plays an important role