Expression of high-mobility group box protein 1 in diabetic foot atherogenesis.

The role of high mobility group box 1 (HMGB1) has been demonstrated in stroke and coronary artery disease but not in peripheral arterial occlusive disease (PAOD). The pathogenesis of HMGB1 in acute and chronic vascular injury is also not well understood. We hypothesized that HMGB1 induces inflammatory markers in diabetic PAOD patients. We studied 36 diabetic patients, including 29 patients with PAOD, who had undergone amputation for diabetic foot and 7 nondiabetic patients who had undergone amputation after traumatic injury. Expression of HMGB1 and inflammatory markers were quantified using immunohistochemical staining. Mitochondrial DNA copy number was quantified using real-time polymerase chain reaction. Compared with that in the traumatic amputation group, HMGB1 expression in vessels was significantly higher in the diabetes and diabetic PAOD groups. In all subjects, arterial stenosis grade was positively correlated with the expression levels of HMGB1, 8-hydroxyguanosine, malondialdehyde, vascular cell adhesion molecule 1, and inflammatory markers CD3, and CD68 in both the intima and the media of vessels. Furthermore, HMGB1 expression level was positively correlated with 8-hydroxyguanosine, vascular cell adhesion molecule 1, nuclear factor-kB, CD3, and CD68 expression. Within the PAOD subgroup, subjects with HMGB1 expression had higher expression of the autophagy marker LC3A/B and higher mitochondrial DNA copy number. HMGB1 may be an inflammatory mediator with roles in oxidative damage and proinflammatory and inflammatory processes in diabetic atherogenesis. Moreover, it may have dual effects by compensating for increased mitochondrial DNA copy number and increased autophagy marker expression.

Local capsaicin application to the stellate ganglion and stellatectomy attenuate neurogenic inflammation in rat bronchi.

The present study investigated the contributions of vagal and nonvagal sensory nerve fibers on neurogenic inflammation in rat bronchial airways. A surgical procedure was developed via the rat mediastinum ventral intercostal space to prepare an intercostal opening without causing pneumothorax for performing stellate ganglionectomy alone, thoracic vagus nerve section alone, and stellatectomy plus thoracic vagotomy, and for injecting capsaicin (2 microl, 10 mg/ml) and 6-hydroxydopamine (2 microl, 50 mg/ml) into the ganglion. One week later in our procedure, we investigated if neurogenic inflammation induced by an intravenous injection of capsaicin (300 nmol/ml/kg) and innervation density of substance P-immunoreactive sensory axons could be decreased after chronic denervation in the rat lower airways. The major findings were that surgical removal of the right stellate ganglion and local capsaicin application resulted in a significant attenuation of neurogenic plasma extravasation in the right bronchial tree evoked by systemic capsaicin application. Reduction of neurogenic plasma extravasation was totally abolished by combined stellatectomy and thoracic vagotomy. The number of substance P-containing axons was also greatly decreased following these surgical and capsaicin treatments. It is concluded that sensory nerve fibers from both vagal source and nonvagal (spinal) source, which associated with the stellate ganglion, contributed significantly to neurogenic inflammation in the bronchial airways with a slightly higher contribution from the vagus nerve.

Thoracic vagus section distal to the recurrent laryngeal nerve reduces substance. P-immunoreactive innervation in the rat bronchial tree.

The vagal nerve trunk in the mediastinum of mammals divides into two main branches, the thoracic vagus nerve and the recurrent laryngeal nerve, in which the sensory nerve axons are largely involved in neurogenic inflammation in the tracheobronchial airways. A previous study demonstrated that cutting the right-side thoracic vagus nerve but not the recurrent laryngeal nerve inhibited capsaicin-induced neurogenic inflammation in the right bronchial tree of the rat. The effect of left thoracic vagus nerve section is still not known. The main purpose of the present study was to investigate the effect of sectioning the right or left thoracic vagus nerve on the innervation density of substance P-immunoreactive axons in bilateral bronchial trees. Following nerve degeneration, the whole mounts of airway tissues were processed with substance P immunohistochemistry. Denervation of either thoracic vagus nerve reduced the innervation density of axons by 38-71% in different parts of the ipsilateral bronchial tree. The effect of right recurrent laryngeal nerve section was less specific; the innervation density was reduced by 21-39% in the trachea and bronchi of both sides. Capsaicin-induced neurogenic plasma leakage was decreased in the left mainstem bronchus and lobar bronchi after left thoracic vagus nerve section. It is concluded that the thoracic vagus nerve largely contributed to the sensory innervation in the ipsilateral bronchial airways and modulated their functions.