Envenomation caused by human contact with the caterpillar Lonomia is characterized by deleterious effects on coagulation and patency of blood vessels. The cellular effects induced by Lonomia obliqua venom highlights its capacity to activate endothelial cells, leading to a proinflammatory phenotype. Having more knowledge about the mechanisms involved in envenomation may contribute to better treatment. We aimed to evaluate the effects of Lonomia obliqua caterpillar bristle extract (LOCBE) on vascular smooth muscle cells (VSMC). We observed that LOCBE induced VSMC migration, which was preceded by alterations in actin cytoskeleton dynamics and Focal Adhesion Kinase activation. LOCBE also induced Extracellular Signal-Regulated Kinase (ERK) phosphorylation in VSMC, and the inhibition of this pathway impaired cell proliferation. Stimulation of VSMC with LOCBE triggered reactive oxygen species (ROS) production through the activation of NADPH oxidase. The rapid increase in these ROS further induced mitochondrial ROS production, however only NADPH oxidase-derived ROS were involved in ERK activation in VSMC. We that demonstrated the chemotactic and proliferative effects of LOCBE on VSMC were dependent on ROS production, mainly through NADPH oxidase. Together, the data show that Lonomia obliqua venom can interact with and activate VSMC. These effects rely on ROS production, suggesting new potential targets for treatment against vascular damage during envenomation.

Background: Diabetic retinopathy (DR) is a chronic diabetic complication occurring in most diabetic patients after 20 years of disease. Progression of DR to its sight threatening stages is usually associated with worsening of underlying retinal vascular dysfunction and disease. The plasma kallikrein kinin system is activated during vascular injury, mediating important functions in inflammation, blood flow, and coagulation. Bradykinin B1 receptor (B1R) is expressed in human retina, and retinal B1R levels are increased in murine models of diabetes. Furthermore, experimental studies reveal that B1R antagonists ameliorate retinal functional abnormalities caused by diabetes in rodents. Thus, B1R gene (BDKRB1) is a candidate gene for DR. Objective: To investigate the association between rs12050217A/G polymorphism in the BDKRB1 gene and DR in patients with type 2 diabetes mellitus (T2DM). Methods: We analyzed 1129 T2DM patients and 416 non-diabetic subjects. T2DM patients were categorized by the presence of non-proliferative DR (NPDR, n=476), proliferative DR (PDR, n=275) and absence of DR (n=200). The local ethic committee approved the study, and all subjects signed a consent form. The BDKRB1 rs12050217A/G polymorphism was genotyped by Real-Time PCR using TaqMan MGB probes. Results: The genotype frequencies of the BDKRB1 rs12050217A/G polymorphism are in Hardy-Weinberg equilibrium, and did not differ between T2DM patients and normoglycemic subjects (P>0.05). The presence of the minor G allele of the rs12050217 polymorphism was less frequent mainly in patients with PDR when compared to patients with NPDR and without DR (31.5, 41.8 and 41.2%, P=0.034; respectively). Interestingly, we observed that the presence of the G allele was associated with protection for PDR, which was confirmed after correction for the presence of hypertension, ethnicity, diabetes duration and age ((95% CI) =0.580 (0.398–0.843); P=0.004). Conclusions: The BDKRB1 rs12050217 G allele is associated with protection for the advanced stage of DR in T2DM patients.