MD A8: Impact of angiotensin II type 1 receptor antibodies on endothelial dysfunction in systemic sclerosis
Systemic sclerosis (SSc), a chronic autoimmune disease, is characterized by skin and internal organs fibrosis, dysregulation of autoimmunity, and microvascular dysfunction. Emerging evidence indicates that autoantibodies (abs) directed against G protein-coupled receptors (GPCRs) are involved in modulating pathological mechanisms in SSc.1Endothelial dysfunction is central in the early pathogenesis of SSc.3 Under physiological conditions, the upper layer of endothelial cells, the glycocalyx (eGC), exhibits an upright and soft conformation, whereas pathophysiological conditions induce a flat and/or stiff eGC.4 Changes of the eGC are considered as a sign of endothelial cell dysfunction.3 It has been shown that isolated IgG containing angiotensin II type I receptor (AT1R) abs from patients with SSc induces activation of human microvascular endothelial cells in vitro2 , which may cause endothelial dysfunction. Thus, this project aims to investigate the effects of AT1R antibodies on structural features of the eGC. Structural features of the eGC of human umbilical vein endothelial cells (HUVECs) will be assessed using atomic force microscopy (AFM), a nanoindentation technique, after treatment with a monoclonal AT1R antibody as well as IgG from SSc patients and healthy controls. Moreover, functional tests such as neutrophil adhesion assay will be performed to investigate further whether altered eGC of activated endothelial cells might facilitate the adhesion of immune cells. A deeper insight into the relationship between AT1R abs and the eGC could improve our understanding of the pathophysiology of SSc.
References:
1. Akbarzadeh R, et al. Front Immunol. 2023;14:1213804.
2. Kill A, et al. Arthritis Res Ther. 2014; 10.1186/ar4457
3. Altorok N, et al., Curr Opin Rheumatol. 2014; 10.1097/BOR.0000000000000112 4. Cosgun ZC, et al. Am J Pathol. 2020;10.1016/j.ajpath.2019.07.021
5. Giil LM, et al. J Alzheimers Dis. 10.3233/JAD-170882
6. Yue X, et al. Ann Rheum Dis. doi:10.1136/annrheumdis-2021-222088
- Projects
- 1st Generation
- A: Defining Autoimmune Pre-Disease
- B: Targeting of Autoimmune Pre-Disease
- Associated projects
- Medical doctoral researcher projects
- Concluded projects
- Doctoral researchers
- Medical doctoral researchers
- MD A1: Investigation of the influence of specific CDK inhibitors on neutrophil activation
- MD A2: Anatomical expression of target antigens in autoimmune blistering dermatoses as markers for lesion formation
- MD A3: Structural characterization of skin-directed autoantibodies and their interaction with the antigen to gain insights into autoimmune pre-disease
- MD A4: Do interactions between AT1R autoantibodies derived from patients with systemic sclerosis and endothelial cells lead to endothelial dysfunction?
- MD A5: Establishing a human 3D skin model for pemphigus vulgaris
- MD A6: Assessing vasculopathy in systemic sclerosis using optical coherence tomography
- MD A7: Identification of autoantibodies contributing to the break of immunotolerance in immunization induced mucous membrane pemphigus mouse model
- MD A8: Impact of angiotensin II type 1 receptor antibodies on endothelial dysfunction in systemic sclerosis
- MD A9: Impact of glycosylation on IgG4-induced signaling in neutrophils
- MD A10: Testing a new single chain variable fragment for pemphigus foliaceus in the human skin organ culture model
- MD A11: Impact of glycosylation on IgG3-induced signaling in neutrophiles
- MD A12: Screening for inhibitors to prevent keratinocyte dissociation
- MD A13: Investigation of the local and systemic complement activation in bullous pemphigoid patients
- MD A14: Impact of different IgG subclasses and glycosylation patterns on immune complex-induced signaling in neutrophils
- MD A15: Novel target antigens of the lower basal membrane zone as inducers of autoimmunity of bullous autoimmune dermatoses
- MD A16: Identification of the major epitope of the BP180 ectodomain recognized by serum IgA autoantibodies of patients with pemphigoid diseases – IgA autoantibodies as prognostic marker?
- MD A17: Autoantibody-mediated effects on endothelial and immune cell signaling in systemic sclerosis
- MD A18: Molecular and cellular characterization of pre-autoimmune effects induced by aging in mice
- MD A19: Immunogenic effects of Staphylococcus aureus toxins in autoimmune vasculitis
- MD B1: Testing the effect of kinase inhibitors in the human skin organ culture model for pemphigus vulgaris
- MD B2: Investigation of cigarette smoking-induced autoantibodies against human airway epithelial cells in patients with chronic obstructive lung disease
- MD B3: Contribution of taurine, pyridoxine and pantothenic acid to the pathomechanism of pemphigus vulgaris
- MD B4: The influence of prednisolone treatment on split formation in the human skin organ culture model for pemphigus vulgaris
- MD B5: Molecular characterization of the pre-autoimmune effects of Western diet in healthy mice
- MD B6: Testing established MAP kinase inhibitors in a different approach of the human skin organ culture model for pemphigus vulgaris
- MD B7: Testing the effect of kinase inhibitors in the human skin organ culture model for pemphigus foliaceus
- Ass. doctoral researchers
- Ass. medical doctoral researchers
- 2nd Generation
- 1st Generation
Medical doctoral researcher
Participating Researchers
Mentors
