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Article ; Online: What Makes Antibodies Against G Protein-Coupled Receptors so Special? A Novel Concept to Understand Chronic Diseases

Gabriela Riemekasten / Frank Petersen / Harald Heidecke

Frontiers in Immunology, Vol

2020 Volume 11

Abstract: Expressions of G protein-coupled receptors (GPCR) on immune and tissue resident cells are the consequence of the cellular environment, which is highly variable. As discussed here, antibodies directed to GPCR (GPCR abs), their levels and correlations to ... ...

Abstract	Expressions of G protein-coupled receptors (GPCR) on immune and tissue resident cells are the consequence of the cellular environment, which is highly variable. As discussed here, antibodies directed to GPCR (GPCR abs), their levels and correlations to other abs, serve as biomarkers for various diseases. They also could reflect the individual interplay between the environment and the immune system. Thus, GPCR abs could display pathogenic chronic conditions and could help to identify disease-related pathways. Moreover, by acting as ligands to their corresponding receptors, GPCR abs modulate autoimmune as well as non-autoimmune diseases. This article introduces GPCR abs as drivers for diseases by their capability to induce a specific signaling and by determining immune cell homeostasis. The identification of the individual GPCR ab function is challenging but might be pivotal in the comprehension of the aetiology of diseases. This, hopefully, will lead to the identification of novel therapeutic strategies. This article provides an overview about concepts and recent developments in research. Accordingly, GPCR abs could represent ideal candidates for precision medicine. Here, we introduce the term antibodiom to cover the network of abs with GPCR abs as prominent players.
Keywords	G protein-coupled receptors ; anti-G protein-coupled receptor antibodies ; immune cell homeostasis ; precision medicine ; angiotensin receptor 1 ; Immunologic diseases. Allergy ; RC581-607
Language	English
Publishing date	2020-12-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Autoantibody Release in Children after Corona Virus mRNA Vaccination

Reiner Buchhorn / Carlotta Meyer / Kai Schulze-Forster / Juliane Junker / Harald Heidecke

Vaccines, Vol 9, Iss 1353, p

A Risk Factor of Multisystem Inflammatory Syndrome?

2021 Volume 1353

Abstract: Multisystem inflammatory syndrome (MIS) is a new systemic inflammatory acute onset disease that mainly affects children (MIS-C) and, at a lesser frequency, adults (MIS-A); it typically occurs 3–6 weeks after acute SARS-CoV infection. It has been ... ...

Abstract	Multisystem inflammatory syndrome (MIS) is a new systemic inflammatory acute onset disease that mainly affects children (MIS-C) and, at a lesser frequency, adults (MIS-A); it typically occurs 3–6 weeks after acute SARS-CoV infection. It has been postulated and shown in adults that MIS may occur after SARS-CoV-2 vaccination (MIS-V). Our current case is one of the first published cases with a multisystem inflammatory syndrome in an 18-year-old adolescent after the SARS-CoV-2 vaccine from Pfizer/BionTech (BNT162b2), who fulfills the published level 1 criteria for a definitive disease: age < 21 years, fever > 3 consecutive days, pericardial effusion, elevated CRP/NT-BNP/Troponin T/D-dimeres, cardiac involvement, and positive SARS-CoV-2 antibodies. The disease starts 10 weeks after the second vaccination, with a fever (up to 40 °C) and was treated with amoxicillin for suspected pneumonia. The SARS CoV-2-PCR and several antigen tests were negative. With an ongoing fever, he was hospitalized 14 days later. A pericardial effusion (10 mm) was diagnosed by echocardiography. The C-reactive protein (174 mg/L), NT-BNP (280 pg/mL), and Troponin T (28 pg/mL) values were elevated. Due to highly elevated D-dimeres (>35,000 μg/L), a pulmonary embolism was excluded by thoracal computer tomography. If the boy did not improve with intravenous antibiotics, he was treated with intravenous immunoglobulins; however, the therapy was discontinued after 230 mg/kg if he developed high fever and hypotension. A further specialized clinic treated him with colchicine and ibuprofen. The MIS-V was discovered late, 4 months after the onset of the disease. As recently shown in four children with MIS-C after SARS-CoV-2 infection and a girl with Hashimoto thyroiditis after BNT162b2 vaccination, we found elevated functional autoantibodies against G-protein-coupled receptors that may be important for pathophysiology but are not conclusive for the diagnosis of MIS-C. Conclusion: We are aware that a misattribution of MIS-V as a severe ...
Keywords	COVID-19 ; autoantibodies ; children ; multisystem inflammatory syndrome ; SARS-CoV-2 vaccination ; Hashimoto thyroiditis ; Medicine ; R
Subject code	610
Language	English
Publishing date	2021-11-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The Prevalence of Hearing Impairments in Women with Silicone Breast Implants

Assaf Greenbaum / Gilad Halpert / Arad Dotan / Shaked Shivatzki / Harald Heidecke / Ricky Kaplan Neeman / Michael Ehrenfeld / Amit Wolfovitz / Howard Amital / Yael Henkin / Yehuda Shoenfeld

Diseases, Vol 11, Iss 31, p

2023 Volume 31

Abstract: Many women with silicone breast implants (SBIs) report non-specific complaints, including hearing impairments. Hearing impairment appears to be associated with a number of autoimmune conditions. The current study aimed to evaluate the prevalence and ... ...

Abstract	Many women with silicone breast implants (SBIs) report non-specific complaints, including hearing impairments. Hearing impairment appears to be associated with a number of autoimmune conditions. The current study aimed to evaluate the prevalence and severity of hearing impairments among women with SBIs and to explore potential improvements in their hearing capability following implant removal. Symptomatic women with SBIs ( n = 160) underwent an initial anamnestic interview, and women who reported hearing impairments were selected for the study. These women completed self-report telephone questionnaires regarding their hearing difficulties. Some of these women underwent subjective and objective hearing tests. Out of 159 (50.3%) symptomatic women with SBIs, 80 reported hearing impairments, including hearing loss (44/80; 55%) and tinnitus (45/80; 56.2%). Five out of seven (71.4%) women who underwent an audiologic evaluation exhibited hearing loss. Of women who underwent silicone implant removal, 27 out of 47 (57.4%) reported the improvement or resolution of their hearing complaints. In conclusion, hearing impairment is a frequent complaint among symptomatic women with SBIs, and tinnitus was found to be the most common complaint. A significant reduction in hearing difficulties was observed following silicone implant removal. Further studies using larger populations are needed to verify the occurrence of hearing impairments in these women.
Keywords	silicone breast implants ; hearing impairments ; tinnitus ; autoimmune/inflammatory syndrome induced by adjuvants (ASIA) ; autoimmunity ; autonomic nervous system ; Medicine ; R
Language	English
Publishing date	2023-02-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Functional IgG Autoantibodies against Autonomic Nervous System Receptors in Symptomatic Women with Silicone Breast Implants

Efrosiniia Talalai / Denis Gorobets / Gilad Halpert / Avishai M. Tsur / Harald Heidecke / Yair Levy / Abdulla Watad / Miri Blank / Izhak Michaelevski / Yehuda Shoenfeld / Howard Amital

Cells, Vol 12, Iss 1510, p

2023 Volume 1510

Abstract: The association between the clinical picture of symptomatic women with silicone breast implants (SBI) and dysregulated immunity was in dispute for decades. In the current study, we describe for the first time the functional activity of purified IgG ... ...

Abstract	The association between the clinical picture of symptomatic women with silicone breast implants (SBI) and dysregulated immunity was in dispute for decades. In the current study, we describe for the first time the functional activity of purified IgG antibodies derived from symptomatic women with SBIs (suffering from subjective/autonomic-related symptoms), both in vitro and in vivo. We found that IgGs, derived from symptomatic women with SBIs, dysregulate inflammatory cytokines (TNFα, IL-6) in activated human peripheral blood mononuclear cells, compared to healthy-women-derived IgGs. Importantly, behavioral studies conducted following intracerebroventricular injection of IgGs derived from symptomatic women with SBIs (who have dysregulated circulating level of IgG autoantibodies directed against autonomic nervous system receptors) into mice brains demonstrated a specific and transient significant increment (about 60%) in the time spent at the center of the open field arena compared with mice injected with IgG from healthy women (without SBIs). This effect was accompanied with a strong trend of reduction of the locomotor activity of the SBI-IgG treated mice, indicating an overall apathic-like behavior. Our study is the first to show the potential pathogenic activity of IgG autoantibodies in symptomatic women with SBIs, emphasizing the importance of these antibodies in SBI-related illness.
Keywords	silicone breast implants ; autoantibodies ; autonomic nervous system ; dysautonomia ; G-protein coupled-receptors ; Biology (General) ; QH301-705.5
Subject code	150
Language	English
Publishing date	2023-05-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Autoantibodies from Patients with Scleroderma Renal Crisis Promote PAR-1 Receptor Activation and IL-6 Production in Endothelial Cells

Michèle Simon / Christian Lücht / Isa Hosp / Hongfan Zhao / Dashan Wu / Harald Heidecke / Janusz Witowski / Klemens Budde / Gabriela Riemekasten / Rusan Catar

International Journal of Molecular Sciences, Vol 22, Iss 11793, p

2021 Volume 11793

Abstract: Background. Scleroderma renal crisis (SRC) is a life-threatening complication of systemic sclerosis (SSc). Autoantibodies (Abs) against endothelial cell antigens have been implicated in SSc and SRC. However, their detailed roles remain poorly defined. ... ...

Abstract	Background. Scleroderma renal crisis (SRC) is a life-threatening complication of systemic sclerosis (SSc). Autoantibodies (Abs) against endothelial cell antigens have been implicated in SSc and SRC. However, their detailed roles remain poorly defined. Pro-inflammatory cytokine interleukin-6 (IL-6) has been found to be increased in SSc, but its role in SRC is unclear. Here, we aimed to determine how the autoantibodies from patients with SSc and SRC affect IL-6 secretion by micro-vascular endothelial cells (HMECs). Methods. Serum IgG fractions were isolated from either SSc patients with SRC (n = 4) or healthy individuals (n = 4) and then each experiment with HMECs was performed with SSc-IgG from a separate patient or separate healthy control. IL-6 expression and release by HMECs was assessed by quantitative reverse transcription and quantitative PCR (RT-qPCR) and immunoassays, respectively. The mechanisms underlying the production of IL-6 were analyzed by transient HMEC transfections with IL-6 promoter constructs, electrophoretic mobility shift assays, Western blots and flow cytometry. Results. Exposure of HMECs to IgG from SSc patients, but not from healthy controls, resulted in a time- and dose-dependent increase in IL-6 secretion, which was associated with increased AKT, p70S6K, and ERK1/2 signalling, as well as increased c-FOS/AP-1 transcriptional activity. All these effects could be reduced by the blockade of the endothelial PAR-1 receptor and/or c-FOS/AP-1silencing. Conclusions. Autoantibodies against PAR-1 found in patients with SSc and SRC induce IL-6 production by endothelial cells through signalling pathways controlled by the AP-1 transcription factor. These observations offer a greater understanding of adverse endothelial cell responses to autoantibodies present in patients with SRC.
Keywords	systemic sclerosis ; scleroderma renal crisis ; PAR-1 receptor ; IL-6 ; autoantibodies ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	616
Language	English
Publishing date	2021-10-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Specific Autoantibodies in Neovascular Age-Related Macular Degeneration

Michelle Prasuhn / Caroline Hillers / Felix Rommel / Gabriela Riemekasten / Harald Heidecke / Khaled Nassar / Mahdy Ranjbar / Salvatore Grisanti / Aysegül Tura

Journal of Personalized Medicine, Vol 11, Iss 1207, p

Evaluation of Morphological and Functional Progression over Five Years

2021 Volume 1207

Abstract: 1) Background: Altered levels of autoantibodies (aab) and their networks have been identified as biomarkers for various diseases. Neovascular age-related macular degeneration (nAMD) is a leading cause for central vision loss worldwide with highly ... ...

Abstract	(1) Background: Altered levels of autoantibodies (aab) and their networks have been identified as biomarkers for various diseases. Neovascular age-related macular degeneration (nAMD) is a leading cause for central vision loss worldwide with highly variable inter- and intraindividual disease courses. Certain aab networks could help in daily routine to identify patients with a high disease activity who need to be visited and treated more regularly. (2) Methods: We analyzed levels of aab against Angiotensin II receptor type 1 (AT1-receptor), Protease-activated receptors (PAR1), vascular endothelial growth factor (VEGF) -A, VEGF-B, and VEGF-receptor 2 in sera of 164 nAMD patients. In a follow-up period of five years, we evaluated changes in functional and morphological characteristics. Using correlation analyses, multiple regression models, and receiver operator characteristics, we assessed whether the five aab have a clinical significance as biomarkers that correspond to the clinical properties. (3) Results: Neither the analyzed aab individually nor taken together as a network showed statistically significant results that would allow us to draw conclusions on the clinical five-year course in nAMD patients. (4) Conclusions: The five aab that we analyzed do not correspond to the clinical five-year course of nAMD patients. However, larger, prospective studies should reevaluate different and more aab to gain deeper insights.
Keywords	autoantibodies ; age-related macular degeneration ; biomarkers ; AT1-receptor ; PAR1 ; VEGF-A ; Medicine ; R
Subject code	616 ; 610
Language	English
Publishing date	2021-11-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Nailfold Videocapillaroscopy for Non-Invasive Assessment of Microcirculation and Prognostic Correlation with Endothelial Dysfunction, Cardiovascular Risk Factors, and Non-HLA Antibodies in Heart Transplant Recipients

Dorota Sikorska / Dorota Kamińska / Rusan Catar / Dashan Wu / Hongfan Zhao / Pinchao Wang / Julian Kamhieh-Milz / Mirosław Banasik / Mariusz Kusztal / Magdalena Cielecka / Michał Zakliczyński / Rafał Rutkowski / Katarzyna Korybalska / Harald Heidecke / Guido Moll / Włodzimierz Samborski

Journal of Clinical Medicine, Vol 12, Iss 2302, p

A Pilot Study

2023 Volume 2302

Abstract: Early identification of allograft vasculopathy and the concomitant elimination of adverse risk factors is essential for improving the long-term prognosis of heart transplant (HTx) recipients with underlying cardiovascular disease (CVD). The major aim of ... ...

Abstract	Early identification of allograft vasculopathy and the concomitant elimination of adverse risk factors is essential for improving the long-term prognosis of heart transplant (HTx) recipients with underlying cardiovascular disease (CVD). The major aim of this pilot study was to conduct a non-invasive imaging evaluation of the HTx patient microcirculation by employing nailfold video-capillaroscopy (NVC) in a well-characterized patient and control cohort, and to correlate these data with endothelial cell function, accompanied by studies of traditional cardiovascular risk factors and non-HLA antibodies in HTx recipients. Ten patients undergoing HTx (mean age of 38 ± 14 years) were recruited for the study and compared to a control group of 12 well-matched healthy volunteers (mean age 35 ± 5 years) with normal body mass index (BMI). Detailed medical records were collected from all individuals. NVC was performed using CapillaryScope 200 MEDL4N microscope. For functional readout and correlation analysis, endothelial cell network formation in conjunction with measurements of patient serum levels of vascular endothelial growth factor (VEGF) and non-HLA autoantibodies directed against the angiotensin II type-1-receptor (anti-AT1R-Ab), endothelin-1 type-A-receptor (anti-ETAR-Ab), protease-activated receptor-1 (anti-PAR-1-Ab), and VEGF-A (anti-VEGF-A-Ab) were studied. Our NVC analysis found that the average apical loop diameter of nailfold capillaries was significantly increased in HTx recipients ( p = 0.001). In addition, HTx patients with more prominent changes in capillaroscopic patterns were characterized by the presence of traditional cardiovascular risk factors, and HTx patients had increased levels of anti-AT1R-ab, anti-ETAR-ab, and anti-VEGF-A-Ab ( p = 0.017, p = 0.025, and p = 0.003, respectively). Capillary diameters most strongly correlated with elevated serum levels of troponin T and triglycerides (R = 0.69, p = 0.028 and R = 0.81, p = 0.004, respectively). In conclusion, we found that an abnormal NVC pattern in ...
Keywords	nailfold videocapillaroscopy (NVC) ; heart transplantation (HTx) ; cardiac allograft vasculopathy (CAV) ; cardiovascular disease (CVD) risk factors ; non-HLA autoantibodies ; Medicine ; R
Subject code	610 ; 616
Language	English
Publishing date	2023-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Non-HLA Antibodies in Hand Transplant Recipients Are Connected to Multiple Acute Rejection Episodes and Endothelial Activation

Dorota Sikorska / Dorota Kamińska / Rusan Catar / Mirosław Banasik / Harald Heidecke / Kai Schulze-Forster / Katarzyna Korybalska / Rafał Rutkowski / Joanna Łuczak / Jerzy Jabłecki / Andrzej Oko / Przemysław Daroszewski / Mariusz Kusztal / Włodzimierz Samborski

Journal of Clinical Medicine, Vol 11, Iss 833, p

2022 Volume 833

Abstract: The role of anti-HLA antibodies in transplant rejection is well-known but the injury associated with non-HLA antibodies is now widely discussed. The aim of our study was to investigate a role of non-HLA antibodies in hand allografts rejection. The study ... ...

Abstract	The role of anti-HLA antibodies in transplant rejection is well-known but the injury associated with non-HLA antibodies is now widely discussed. The aim of our study was to investigate a role of non-HLA antibodies in hand allografts rejection. The study was performed on six patients after hand transplantation. The control group consisted of: 12 kidney transplant recipients and 12 healthy volunteers. The following non-HLA antibodies were tested: antibody against angiotensin II type 1 receptor (AT1R-Ab), antibody against endothelin-1 type-A-receptor (ETAR-Ab), antibody against protease-activated receptor 1 (PAR-1-Ab) and anti-VEGF-A antibody (VEGF-A-Ab). Chosen proinflammatory cytokines (Il-1, IL-6, IFNγ) were used to evaluate the post-transplant humoral response. Laboratory markers of endothelial activation (VEGF, sICAM, vWF) were used to assess potential vasculopathy. The patient with the highest number of acute rejections had both positive non-HLA antibodies: AT1R-Ab and ETAR-Ab. The same patient had the highest VEGF-A-Ab and very high PAR1-Ab. All patients after hand transplantation had high levels of laboratory markers of endothelial activation. The existence of non-HLA antibodies together with multiple acute rejections observed in patient after hand transplantation should stimulate to look for potential role of non-HLA antibodies in humoral injury in vascular composite allotransplantation.
Keywords	hand transplantation ; non-HLA antibodies ; rejection ; vasculopathy ; vascularized composite allotransplantation ; Medicine ; R
Subject code	616 ; 570
Language	English
Publishing date	2022-02-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Autoantibodies Targeting AT 1 - and ET A -Receptors Link Endothelial Proliferation and Coagulation via Ets-1 Transcription Factor

Rusan Catar / Melanie Herse-Naether / Nan Zhu / Philine Wagner / Oskar Wischnewski / Angelika Kusch / Julian Kamhieh-Milz / Andreas Eisenreich / Ursula Rauch / Björn Hegner / Harald Heidecke / Angela Kill / Gabriela Riemekasten / Gunnar Kleinau / Patrick Scheerer / Duska Dragun / Aurelie Philippe

International Journal of Molecular Sciences, Vol 23, Iss 244, p

2022 Volume 244

Abstract: Scleroderma renal crisis (SRC) is an acute life-threatening manifestation of systemic sclerosis (SSc) caused by obliterative vasculopathy and thrombotic microangiopathy. Evidence suggests a pathogenic role of immunoglobulin G (IgG) targeting G-protein ... ...

Abstract	Scleroderma renal crisis (SRC) is an acute life-threatening manifestation of systemic sclerosis (SSc) caused by obliterative vasculopathy and thrombotic microangiopathy. Evidence suggests a pathogenic role of immunoglobulin G (IgG) targeting G-protein coupled receptors (GPCR). We therefore dissected SRC-associated vascular obliteration and investigated the specific effects of patient-derived IgG directed against angiotensin II type 1 (AT 1 R) and endothelin-1 type A receptors (ET A R) on downstream signaling events and endothelial cell proliferation. SRC-IgG triggered endothelial cell proliferation via activation of the mitogen-activated protein kinase (MAPK) pathway and subsequent activation of the E26 transformation-specific-1 transcription factor (Ets-1). Either AT 1 R or ET A R receptor inhibitors/shRNA abrogated endothelial proliferation, confirming receptor activation and Ets-1 signaling involvement. Binding of Ets-1 to the tissue factor (TF) promoter exclusively induced TF. In addition, TF inhibition prevented endothelial cell proliferation. Thus, our data revealed a thus far unknown link between SRC-IgG-induced intracellular signaling, endothelial cell proliferation and active coagulation in the context of obliterative vasculopathy and SRC. Patients’ autoantibodies and their molecular effectors represent new therapeutic targets to address severe vascular complications in SSc.
Keywords	angiotensin ; renin–angiotensin system ; endothelin-1 ; systemic sclerosis ; renal crisis ; autoantibodies ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	616
Language	English
Publishing date	2022-12-01T00:00:00Z
Publisher	MDPI AG
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Article ; Online: Molecular Effects of Auto-Antibodies on Angiotensin II Type 1 Receptor Signaling and Cell Proliferation

Aurélie Philippe / Gunnar Kleinau / Jason Jannis Gruner / Sumin Wu / Daniel Postpieszala / David Speck / Harald Heidecke / Simon J. Dowell / Gabriela Riemekasten / Peter W. Hildebrand / Julian Kamhieh-Milz / Rusan Catar / Michal Szczepek / Duska Dragun / Patrick Scheerer

International Journal of Molecular Sciences, Vol 23, Iss 3984, p

2022 Volume 3984

Abstract: The angiotensin II (Ang II) type 1 receptor (AT 1 R) is involved in the regulation of blood pressure (through vasoconstriction) and water and ion homeostasis (mediated by interaction with the endogenous agonist). AT 1 R can also be activated by auto- ... ...

Abstract	The angiotensin II (Ang II) type 1 receptor (AT 1 R) is involved in the regulation of blood pressure (through vasoconstriction) and water and ion homeostasis (mediated by interaction with the endogenous agonist). AT 1 R can also be activated by auto-antibodies (AT 1 R-Abs), which are associated with manifold diseases, such as obliterative vasculopathy, preeclampsia and systemic sclerosis. Knowledge of the molecular mechanisms related to AT 1 R-Abs binding and associated signaling cascade (dys-)regulation remains fragmentary. The goal of this study was, therefore, to investigate details of the effects of AT 1 R-Abs on G-protein signaling and subsequent cell proliferation, as well as the putative contribution of the three extracellular receptor loops (ELs) to Abs-AT 1 R signaling. AT 1 R-Abs induced nuclear factor of activated T-cells (NFAT) signaling, which reflects G q/11 and G i activation. The impact on cell proliferation was tested in different cell systems, as well as activation-triggered receptor internalization. Blockwise alanine substitutions were designed to potentially investigate the role of ELs in AT 1 R-Abs-mediated effects. First, we demonstrate that Ang II-mediated internalization of AT 1 R is impeded by binding of AT 1 R-Abs. Secondly, exclusive AT 1 R-Abs-induced G q/11 activation is most significant for NFAT stimulation and mediates cell proliferation. Interestingly, our studies also reveal that ligand-independent, baseline AT 1 R activation of G i signaling has, in turn, a negative effect on cell proliferation. Indeed, inhibition of G i basal activity potentiates proliferation triggered by AT 1 R-Abs. Finally, although AT 1 R containing EL1 and EL3 blockwise alanine mutations were not expressed on the human embryonic kidney293T (HEK293T) cell surface, we at least confirmed that parts of EL2 are involved in interactions between AT 1 R and Abs. This current study thus provides extended insights into the molecular action of AT 1 R-Abs and associated mechanisms of interrelated pathogenesis.
Keywords	angiotensin II type 1 receptor ; AT 1 R ; auto-antibodies ; G protein-coupled receptors ; systemic sclerosis ; angiotensin ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	290
Language	English
Publishing date	2022-04-01T00:00:00Z
Publisher	MDPI AG
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