Thomas Unger

Thomas Unger
Maastricht University | UM · CARIM School for Cardiovascular Diseases

MD PhD

About

1,012
Publications
84,691
Reads
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40,311
Citations
Additional affiliations
April 2012 - present
Maastricht University
Position
  • Managing Director
April 2001 - April 2012
Charité Universitätsmedizin Berlin
Position
  • Managing Director
April 1994 - April 2001
Christian-Albrechts-Universität zu Kiel
Position
  • Managing Director

Publications

Publications (1,012)
Article
Full-text available
The angiotensin AT2 receptor (AT2R) is a main receptor of the protective arm of the renin-angiotensin system and exerts for instance anti-inflammatory effects. The impact of AT2R stimulation on autoimmune diseases such as rheumatoid arthritis (RA) is not yet known. We investigated the therapeutic potential of AT2R-stimulation with the selective non...
Article
Full-text available
The aim of this study was to evaluate the effect of Compound 21 (C21), a selective AT2R agonist, on the prevention of endothelial dysfunction, extracellular matrix (ECM) remodeling and arterial stiffness associated with diet-induced obesity (DIO). 5-week-old male C57BL/6J mice were fed a standard (Chow) or high-fat diet (HF) for 6 weeks. Half of th...
Article
Compound 21 (C21), a selective agonist of angiotensin II type 2 receptor (AT2R), induces vasodilation through NO release. Since AT2R seems to be overexpressed in obesity, we hypothesize that C21 prevents the development of obesity-related vascular alterations. The main goal of the present study was to assess the effect of C21 on thoracic aorta endo...
Article
Full-text available
Introduction Whether ACE inhibitors (ACEi) or angiotensin II receptor blocker (ARB) therapy should be continued, initiated or ceased in patients with COVID-19 is uncertain. Given the widespread use of ACEi/ARBs worldwide, guidance on the use of these drugs is urgently needed. This prospective meta-analysis aims to pool data from randomised controll...
Article
Full-text available
Rationale: Hypertension is a major risk factor for cerebral small vessel disease, the most prevalent cause of vascular cognitive impairment. As we have shown, hypertension induced by a prolonged Angiotensin II infusion is associated with increased permeability of the blood-brain barrier (BBB), chronic activation of microglia and myelin loss. In thi...
Article
Full-text available
Elevated blood pressure remains the single biggest risk factor contributing to the global burden of disease and mortality. May Measurement Month is an annual global screening campaign aiming to improve awareness of blood pressure at the individual and population level. Adults (≥18 years) recruited through opportunistic sampling were screened at sit...
Article
Full-text available
Elevated blood pressure remains the single biggest risk factor contributing to the global burden of disease and mortality. May Measurement Month is an annual global screening campaign aiming to improve awareness of blood pressure at the individual and population level. Adults (≥18 years) recruited through opportunistic sampling were screened at sit...
Article
Elevated blood pressure remains the single biggest risk factor contributing to the global burden of disease and mortality. May Measurement Month is an annual global screening campaign aiming to improve awareness of blood pressure at the individual and population level. Adults ({greater than or equal to}18 years) recruited through opportunistic samp...
Article
Full-text available
Document reviewers: Hind Beheiry (Sudan), Irina Chazova (Russia), Albertino Damasceno (Mozambique), Anna Dominiczak (UK), Anastase Dzudie (Cameroon), Stephen Harrap (Australia), Hiroshi Itoh (Japan), Tazeen Jafar (Singapore), Marc Jaffe (USA), Patricio Jaramillo-Lopez (Colombia), Kazuomi Kario (Japan), Giuseppe Mancia (Italy), Ana Mocumbi (Mozambi...
Article
Full-text available
Brown adipose tissue (BAT) is known to secrete regulatory factors in response to thermo-genic stimuli. Components of the BAT secretome may exert local effects that contribute to BAT recruitment and activation. Here, we found that a thermogenic stimulus leads to enhanced secretion of kininogen (Kng) by BAT, owing to induction of kininogen 2 (Kng2) g...
Preprint
Full-text available
Rationale: Hypertension is a major risk factor for cerebral small vessel disease, the most prevalent cause of vascular cognitive impairment. As we have shown, hypertension induced by a prolonged Ang II infusion is associated with increased permeability of the blood-brain barrier (BBB) and chronic activation of microglia. In this study we therefore...
Article
The actions of angiotensin II (Ang II) are mediated by AT1 and AT2 receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Angiotensin receptors [61, 152]), which have around 30% sequence similarity. The decapeptide angiotensin I, the octapeptide angiotensin II and the heptapeptide angiotensin III are endogenous ligands. losartan, candes...
Article
Full-text available
Objective The receptor MAS, encoded by Mas1, is expressed in microglia and its activation has been linked to anti-inflammatory actions. However, microglia are involved in several different processes in the central nervous system, including the promotion of angiogenesis. We therefore hypothesized that the receptor MAS also plays a role in angiogenes...
Chapter
The renin-angiotensin-aldosterone system (RAAS) represents one of the most important contributors to vascular, cardiac, and renal pathology. Its major effector peptides, notably the octapeptide angiotensin II (AngII), induce vasoconstriction (directly and indirectly via sympathetic activation and vasopressin release) and participate in processes of...
Article
Full-text available
The causal relation between hypertension and cerebral small vessel disease (cSVD) remains elusive, and appropriate animal models are scarce. We aimed to assess the relevance of prolonged angiotensin II-induced hypertension in mice for the study of cSVD. Adult male C57BL/6 mice were continuously infused for 3 months with Angiotensin II (Ang II; 2 µg...
Article
Full-text available
The effects of the selective AT2R (angiotensin AT2 receptor) agonist, Compound 21 (C21), on abdominal aortic aneurysm formation were investigated in normotensive Wistar rats. Abdominal aortic aneurysm was induced by perfusion of isolated aortic segments with elastase. Treatment with C21 (0.03 mg/kg daily) was started after operation and continued f...
Article
Full-text available
Background: Increased blood pressure is the biggest contributor to the global burden of disease and mortality. Data suggest that less than half of the population with hypertension is aware of it. May Measurement Month was initiated to raise awareness of the importance of blood pressure and as a pragmatic interim solution to the shortfall in screen...
Article
Full-text available
Idiopathic Pulmonary Fibrosis (IPF) is a chronic lung disease characterized by scar formation and respiratory insufficiency, which progressively leads to death. Pulmonary hypertension (PH) is a common complication of IPF that negatively impacts clinical outcomes, and has been classified as Group III PH. Despite scientific advances, the dismal progn...
Article
The angiotensin II type 2 receptor (AT2R) and the angiotensin-(1-7) receptor (MasR) play a cardiovascular protective role by counter-regulating angiotensin II type 1 receptor (AT1R)-mediated effects, but whether this involves blunting of adrenocortical hormone secretion is unknown. We investigated the presence of AT1R, AT2R and MasR in aldosterone-...
Chapter
Hormonal systems are largely involved in blood pressure regulation and water and salt hemostasis. Importantly, they are also involved in development and progression of cardiovascular and renal diseases. Here, we discuss recent findings about the impact of renin-angiotensin, aldosterone, vasopressin, and natriuretic peptide systems on blood pressure...
Article
Arterial pressure is age and sex dependent. The angiotensin type 2 receptor (AT 2 R) plays a greater role in the regulation of arterial pressure and renal function in adult females than age-matched males and aging females. In the present study, we investigated the effect of chronic AT 2 R stimulation using the AT 2 R agonist, compound 21 (C21), to...
Article
Full-text available
The renin-angiotensin system (RAS) plays an important role in the initiation and progression of cardiovascular and renal diseases. These actions mediated by AT1 receptor (AT1R) are well established and led to development of selective AT1R blockers (ARBs). In contrast, there is scientific evidence that AT2 receptor (AT2R) mediates effects different...
Article
Full-text available
The renin-angiotensin-system and obesity have been implicated in vascular outward remodeling, including aneurysms, but the precise mechanisms are yet not understood. We investigated the effect of the angiotensin AT1-receptor antagonist telmisartan on aortic outward remodeling in a diet-induced obesity-model in mice. C57/Black6J mice were fed with e...
Article
The angiotensin type 2 receptor (AT2R) and the receptor MAS are receptors of the protective arm of the renin-angiotensin system. They mediate strikingly similar actions. Moreover, in various studies, AT2R antagonists blocked the effects of MAS agonists and vice versa. Such cross-inhibition may indicate heterodimerization of these receptors. Therefo...
Article
Background: The multifactorial origin of cardiovascular diseases has led to polypharmacy in primary and secondary prophylaxis with evidence-based medications, such as statins, antihypertensive drugs and platelet aggregation inhibitors. The number of prescribed drugs correlates inversely to adherence and can lead to treatment failure. Fixed-dose co...
Article
Purpose of review: Angiotensin II is a main regulator of kidney function. Renal actions mediated by the angiotensin AT1 receptor have been well known for many years. In contrast, several details of angiotensin AT2 receptor actions in kidney physiology and pathophysiology were only described very recently. These findings are reviewed in this articl...
Article
Objective: The contribution of hypertension in the pathological cascade of vascular cognitive impairment (VCI) remains elusive, and appropriate models are lacking [1]. We have previously demonstrated an impairment of short-term memory in adult mice exposed to prolonged angiotensin II (Ang II) infusion [2]. We hypothesize that 1) the underlying mec...
Article
The renin-angiotensin system (RAS) plays an important role in the initiation and progression of tissue injuries in the cardiovascular and nervous systems. The detrimental actions of the AT1 receptor (AT1R) in hypertension and vascular injury, myocardial infarction and brain ischemia are well established. In the past twenty-five years, protective ac...
Article
Full-text available
This study investigated the effect of post-stroke, direct AT2-receptor (AT2R) stimulation with the non-peptide AT2R-agonist compound 21 (C21) on infarct size, survival and neurological outcome after middle cerebral artery occlusion (MCAO) in mice and looked for potential underlying mechanisms. C57/BL6J or AT2R-knockout mice (AT2-KO) underwent MCAO...
Article
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Aims/hypothesis: Angiotensin II is well-recognised to be a key mediator in driving the pathological events of diabetes-associated atherosclerosis via signalling through its angiotensin II type 1 receptor (AT1R) subtype. However, its actions via the angiotensin II type 2 receptor (AT2R) subtype are still poorly understood. This study is the first t...
Article
Since its discovery, 25 years ago, the angiotensin AT2 receptor (AT2R) has puzzled the scientific community because of its distinct -localization, regulation, signaling pathways, and biological effects separating it clearly from the classical features of the renin-angiotensin system (RAS) mediated by the angiotensin AT1 receptor. Intensive research...
Article
The AT2 receptor (AT2R) is highly expressed in the nervous system and plays an important role not only in fetal development but also in adult life. During neuronal injuries, including stroke and spinal cord and peripheral nerve damage, a strong upregulation of the AT2R positively correlates with neuroregenerative processes. AT2R stimulation, either...
Article
Full-text available
Cardiovascular and metabolic disorders, such as hypertension, insulin resistance, dyslipidemia or obesity are linked with chronic low-grade inflammation and dysregulation of the renin-angiotensin system (RAS). Consequently, RAS inhibition by ACE inhibitors or angiotensin AT1 receptor (AT1R) blockers is the evidence-based standard for cardiovascular...
Article
Objectifs: La S-nitrosation (fixation d'un résidu NO sur les cystéines des protéines) diminue l'affinité de l'angiotensine II (Ang II) pour ses récepteurs (1). Un pré-traitement par un donneur de NO, le S-nitrosoglutathion (GSNO), abolit spécifiquement la vasoconstriction d'artères cérébrales moyennes (MCA) à l'Ang II (2), suggérant une modificati...
Article
Full-text available
Pulmonary fibrosis (PF) is a fatal disease characterized by scarring of the lung tissue. A dysregulated renin angiotensin system (RAS) has been implicated in the pathology of PF. Recent reports suggest a beneficial role for the angiotensin type II receptor (AT2R) in cardiopulmonary disorders; however, the effects of AT2R in PF have not been studied...
Article
Full-text available
Diabetes is a common and rapidly growing disease that affects more than 380 million people worldwide and is an established risk factor for cardiovascular disease with differential effects on women compared to men. While the general population of women, particularly young women, has more favourable cardiovascular risk profiles than men, this protect...
Article
Cognitive impairment is a major disability increasing due to population ageing. Hypertension is a major risk factor for the development of vascular cognitive impairment. However the contribution of hypertension in the pathological cascade of vascular cognitive impairment remains elusive. Although few cardiovascular models have shown to be relevant...
Article
Full-text available
Myocardial infarction (MI) is a major condition causing heart failure (HF). After MI, the renin angiotensin system (RAS) and its signalling octapeptide angiotensin II (Ang II) interferes with cardiac injury/repair via the AT1 and AT2 receptors (AT1R, AT2R). Our study aimed at deciphering the mechanisms underlying the link between RAS and cellular c...
Article
The hemodynamic and nonhemodynamic effects of angiotensin II on diabetic complications are considered to be primarily mediated by the angiotensin II type 1 receptor subtype. However, its biological and functional effect mediated through the angiotensin II type 2 receptor subtype is still unclear. Activation of the angiotensin II type 2 receptors ha...
Article
Full-text available
Recently, AT2 receptors have been discovered on the surface of human immunocompetent cells such as monocytes. Data on regulative properties of this receptor on the cellular immune response are poor. We hypothesized that direct stimulation of the AT2 receptor mediates anti-inflammatory responses in these cells. Human monocytic THP-1 and U937 cells w...
Article
In most situations, the angiotensin AT2-receptor (AT2R) mediates physiological actions opposing those mediated by the AT1-receptor (AT1R), including a vasorelaxant effect. Nevertheless, experimental evidence vastly supports that systemic application of AT2R-agonists is blood pressure neutral. However, stimulation of AT2R locally within the brain or...
Article
Full-text available
The angiotensin type 2 receptor (AT2R) and the receptor Mas are components of the protective arms of the renin-angiotensin system (RAS), i.e. they both mediate tissue protective and regenerative actions. The spectrum of actions of these two receptors and their signalling mechanisms display striking similarities. Moreover, in some instances, antagon...
Article
Elevated systolic blood pressure (SBP) correlates to cognitive decline and incident dementia. The effects of heart rate (HR), visit to visit HR variation, and visit to visit SBP variation are less well established. Patients without preexisting cognitive dysfunction (N=24 593) were evaluated according to mean SBP, SBP visit to visit variation (coeff...
Article
Full-text available
Background The angiotensin AT2 (AT2R) is upregulated in disease states such as atherosclerosis; with blockade of the AT2R shown to exacerbate plaque formation. Direct stimulation of the AT2R has been shown to be anti-atherogenic but the mechanisms and pathways involved remain unknown.PurposeTo examine the effect of direct AT2R stimulation on the le...
Article
The Protective Arm of the Renin Angiotensin System: Functional Aspects and Therapeutic Implications is the first comprehensive publication to signal the protective role of a distinct part of the renin-angiotensin system (RAS), providing readers with early insight into a complex system which will become of major medical importance in the near future...
Article
Renin is a key enzyme of the renin-angiotensin-aldosterone-system (RAAS), a complex hormone system which regulates the sodium balance, the blood vessel tone and the glomerular filtration. Therefore, it plays a crucial role in the pathology of hypertension. This chapter reviews the structure, the biosynthesis, the processing and the expression of re...
Article
Pulmonary hypertension (PH) is a devastating disease characterized by increased pulmonary arterial pressure, which progressively leads to right heart failure and death. A dysregulated renin angiotensin system (RAS) has been implicated in the development and progression of PH. However, the role of the angiotensin type II receptor (AT2 receptor) in P...
Article
The presence of AT2 receptors in mitochondria and their role in NO generation and cell aging were recently demonstrated in various human and mouse non-tumour cells. We investigated the intracellular distribution of AT2 receptors including their presence in mitochondria and the role in the induction of apoptosis and cell death in cultured human uter...