ABSTRACT
The protective effects of male hormones on the cardiovascular system are still in dispute. There is now ample evidence that testosterone level is negatively correlated to the incidence and mortality of cardiovascular disease in men. Endothelial progenitor cells (EPCs) play a vital role in endothelial healing and vascular integrity, which are useful for promoting cardiovascular health. In this study, we investigated the effects of dihydrotestosterone (DHT), a non-aromatizable androgen, on human EPC function and the activation of the phosphatidylinositol-3-kinase (PI3-K)/Akt pathway in vitro. EPCs were incubated with a series of concentrations (1, 10, or 100 nmol/L in DMSO) of DHT for 24 h or with 10 nmol/L DHT for different time (6, 12, 24, 48 h). EPC adhesion and proliferation and the activation of Akt were assayed by cell counting, 5-ethynyl-2'-deoxyuridine incorporation assay, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and Western blot analysis. Our data demonstrated that DHT significantly increased the proliferative activity and adhesive ability of EPCs in a dose- and time-dependent manner, maximum at 10 nmol/L, 24 h (p < 0.05). Western blot analysis revealed that DHT promoted the phosphorylation of Akt, and the effects of different concentrations of DHT on Akt phosphorylation were consistent with those on EPC proliferation and adhesion (p < 0.05). However, the enhancing effects of DHT on EPCs decreased with administration of the pharmacological PI3-K blocker LY294002 (p < 0.05). In conclusion, DHT can modulate EPC proliferation and adhesion and the PI3-K/Akt pathway plays an important role in this process.
Subject(s)
Cell Adhesion/drug effects , Cell Proliferation/drug effects , Dihydrotestosterone/pharmacology , Endothelial Cells/drug effects , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction/drug effects , Cell Adhesion/physiology , Cell Proliferation/physiology , Dihydrotestosterone/administration & dosage , Dose-Response Relationship, Drug , Endothelial Cells/metabolism , Humans , Male , Stem Cells/drug effects , Stem Cells/metabolismABSTRACT
This study shows the expression pattern of calcitonin gene-related peptide (CGRP) in the anterior and posterior horns of the spinal cord after brachial plexus injury. The animals were divided into three injury groups: group 1, right C(7) anterior root avulsion; group 2, right C(7) anterior root avulsion and cut right C(5)-T(1) posterior roots; and group 3, right C(7) anterior root avulsion plus right hemitransection between the C(5) and C(6) segments of the spinal cord. These animals were killed at 1, 3, 7 and 14 days after injury. In the anterior horn of all three injured groups, the expression of CGRP increased progressively from day 1 to day 7 (p<0.05), peaked on day 7, and then began to decrease slowly. In the posterior horn of all three injured groups, the expression of CGRP decreased gradually from day 1 to day 14 after the operation and was significantly lower on day 14 compared to day 1. At each time point (days 1, 3, 7 and 14), the expression of CGRP was the highest in group 1 and the lowest in group 2, with significant differences among the three groups. The CGRP in the anterior horn of the spinal cord was derived from the cell bodies of motor neurons and was possibly involved in repair mechanisms and regeneration after nerve injury. However, the CGRP in the posterior horn was mainly derived from the posterior root ganglion and was possibly associated with the conduction of noxious stimulation.
Subject(s)
Brachial Plexus Neuropathies/metabolism , Calcitonin Gene-Related Peptide/metabolism , Ganglia, Spinal/metabolism , Nociceptors/metabolism , Spinal Cord/metabolism , Animals , Anterior Horn Cells/cytology , Anterior Horn Cells/metabolism , Biomarkers/analysis , Biomarkers/metabolism , Brachial Plexus Neuropathies/pathology , Brachial Plexus Neuropathies/physiopathology , Denervation , Disease Models, Animal , Ganglia, Spinal/cytology , Ganglia, Spinal/physiopathology , Immunohistochemistry , Male , Motor Neurons/cytology , Motor Neurons/metabolism , Nerve Regeneration/physiology , Nociceptors/cytology , Pain/metabolism , Pain/physiopathology , Posterior Horn Cells/cytology , Posterior Horn Cells/metabolism , Rats , Rats, Sprague-Dawley , Recovery of Function/physiology , Rhizotomy , Sensory Receptor Cells/cytology , Sensory Receptor Cells/metabolism , Spinal Cord/cytology , Spinal Cord/physiopathology , Up-Regulation/physiologyABSTRACT
BACKGROUND: This study aims to obtain the biomechanical properties of ascending aorta and pulmonary trunk between healthy humans and pigs of different months, so as to provide necessary biomechanical experimental basis for anastomosing blood vessel in pig-to-human heart xenotransplantation. METHODS: Ascending aorta and pulmonary trunks of the six deceased donors (male 4, female 2) and 42 Chinese Hubei white pigs aged 1-7 months were performed biomechanical test. The blood vessel was given periodic permanent loading and unloading, and repeated force-deformation data were obtained. The elastic properties of the blood vessels were obtained by curve from experimental data. RESULTS: The biomechanical material constant of ascending aorta and pulmonary trunk of pigs did not increase with the increase of age (F = 14.569, P = 0.126). The biomechanical material constant of humans was basically similar to that of pigs aged 1-7 months (F = 12.264, P = 0.225). The elastic modulus was the biggest in pigs aged 7 months in comparison with that in other ages (F = 27.425, P = 0.032). There was no significant difference of elastic modulus of corresponding blood vessel between humans and pigs of different months (F = 17.328, P = 0.215). CONCLUSIONS: Our present study suggests that there was no significant difference of elastic properties of ascending aorta and pulmonary trunks between humans and pigs. From biomechanical aspects, anastomosis of corresponding ascending aorta and pulmonary trunks in the process of pig-to-human heart xenotransplantation may be feasible.
