A Study On The Pathological Changes Of The Skeletal Muscle Microvessels And Their Pathogenesis In DM/PM

Objective: To study the expression of CD34, VE-cadherin, CD61 and HLA-DR in the skeletal muscle microvessels of dermatomyositis (DM) / polymyositis (PM), the effect of the serum of the DM/PM patients on HUVEC in vitro. We also examined the positive rate of Anti-Endothelial Cells antibodies (AECA) to clarify the pathological changes of microvessels and the pathogenetic mechanism in DM/PM to give new view for earlier diagnosis and pathogenesis.Methods: The expression of CD34, VE-cadherin, CD61 and HLA-DR was detected in the skeletal muscle of DM/PM with the immunohistochemistry compared with normal skeletal muscle from bone surgery. The effect of the serum of patients on HUVEC was examined by MTT assay. AECA in patients with DM/PM was determined by cell-ELISA method.Result: (1) The lower expression of CD34 in the microvascular endothelial cells of skeletal muscle showed a decreased numbers of microvessel in DM. However, its expression in PM was normal; (2) The expression of VE-cadherin reduced in the microvessels in the perifascicular aera of DM patients compared with normal group. And there was an negtive relation to the infliltration of inflammatory cells (r=-0.9278, P<0.0001). But there was no obvious change in PM; (3) The HLA-DR antigens expressed in muscle fibers and blood vessels in 13 out of 16 DM patients (87.5%), 4 out of the 5 PM patients. They expressed only in some endothelial cells in the 9 health controls. (4) The expression of CD61 in the perifascicular area of skeletal muscle was 5 positive and 5 weakly positive in the 16 DM patients(62.5%). And there was only one PM patient with weak expression. The normal group was negative. (5) There was significant difference about the OD values of serum AECA between the DM/PM group and the normal group(0.9078±0.3038 versus 0.4399±0.1820, P=0.000), and there was a positive relevance between the serum AECA and the serum IgM(r=0.5473,P=0.0428). The values of AECA in the patients of DM/PM with ILD were much higer than those without(P=0.035). There was significant difference about the OD values of AECA between the pre-treatment and the post-treatment groups(1.2266±0.3098 versus 0.8701±0.2018, P<0.001). (6) There was no significant difference about the activity of HUVEC between DM/PM group and the normal control group by MTT assay(P>0.05). The serum of the post-treatment group and the AECA-positve group suppressed the proliferation of HUVEC compared with the pre-treatment group after 24h(P<0.05). However There was no significant difference between the pre-treatment group and the post-treatment group after 48h or 72h(P>0.05).Conclusion: (1) The up-regulation of HLA-DR in the skeletal muscle microvessels and fibers in DM/PM suggests it may play a role in the pathogenesis of DM/PM, and it can also provide marker for the diagnosis of DM/PM. (2) The reduction of microvessels in DM/PM indicates that they were injured and decreased. (3)The higer expression of CD61 in skeletal muscle microvessels indicates there is angiogenesis in DM. When combined with the decreased microvessel in DM, it may provide method for distinguishing DM and PM; (4) The expression of VE-cadherin in muscle microvascular endothelial cells in DM/PM patients down-regulated and there was negative relevance to inflammation. The integrity of microvessels is damaged, and it can do favor for the exudation of inflammatory cells and the formation of inflamation. (5) The level of AECA is much higer in serum of patients with DM/PM than the control group, and the level of DM/PM patients with ILD is higher than those without. The level of serum AECA in the patients of post-treatment group went down. The serum AECA may play an important role in the pathological course of DM/PM and the pathogenesis of ILD. The serum AECA could serve as useful indicators for disease activity and the efficacy of treatment. (6) The serum of DM/PM patients had no effect on the activity of HUVEC in vitro. However, the serum of the AECA-positve and the post-treatment DM/PM patients may inhibit the proliferation of HUVEC after 24h.