A5042047227- Sirtuins and Resveratrol in Medicine
- MicroRNA in disease regulation
- Circular RNAs in diseases
- Adipose Tissue and Metabolism
- Autophagy in Disease and Therapy
- Cancer-related molecular mechanisms research
- Endoplasmic Reticulum Stress and Disease
- Cardiac Ischemia and Reperfusion
- PARP inhibition in cancer therapy
- Minimally Invasive Surgical Techniques
- Aortic Disease and Treatment Approaches
- Intestinal Malrotation and Obstruction Disorders
- Advanced biosensing and bioanalysis techniques
- Regulation of Appetite and Obesity
- Cancer-related Molecular Pathways
- Aortic aneurysm repair treatments
- Cerebrovascular and genetic disorders
- RNA Interference and Gene Delivery
- Renal and Vascular Pathologies
- Adipokines, Inflammation, and Metabolic Diseases
- Mechanical Circulatory Support Devices
- Sepsis Diagnosis and Treatment
- Lipid Membrane Structure and Behavior
- Muscle Physiology and Disorders
- Abdominal Surgery and Complications
University of Freiburg
2015-2025
Universitäts-Herzzentrum Freiburg-Bad Krozingen
2021-2025
Max Planck Institute for Heart and Lung Research
2008-2022
University Medical Center Freiburg
1993-2021
University Medical Center Utrecht
2015-2017
Sirt7 is a member of the mammalian sirtuin family consisting 7 genes, Sirt1 to Sirt7, which all share homology founding member, yeast Sir2 gene. Most sirtuins are supposed act as histone/protein deacetylases, use oxidized NAD in sirtuin-specific, 2-step deacetylation reaction. To begin decipher biological role we inactivated gene mice. Sirt7-deficient animals undergo reduction mean and maximum lifespans develop heart hypertrophy inflammatory cardiomyopathy. mutant hearts also characterized...
Significance This paper describes a mechanism of regulation Sirt1 activity by Sirt7. Deacetylases and Sirt7 belong to the mammalian family seven sirtuins, which play important regulatory roles in several biological processes such as metabolism aging. We discovered that is able augment its own catalytical autodeacetylation. binds inhibits activity. The importance this was revealed differentiation maintenance white adipose tissue (WAT). knockout mice contain significantly diminished amount WAT...
The interaction of circulating cells within the vascular wall is a critical event in chronic inflammatory processes, such as atherosclerosis, but control state still largely unclear.This study was undertaken to characterize function endothelial-enriched microRNA miR-100 during inflammation and atherogenesis.Based on transcriptome analysis endothelial after overexpression, we identified potent suppressor adhesion molecule expression, resulting attenuated leukocyte-endothelial vitro vivo shown...
Background— Adaptive neovascularization after arterial occlusion is an important compensatory mechanism in cardiovascular disease and includes both the remodeling of pre-existing vessels to collateral arteries (arteriogenesis) angiogenic capillary growth. We now aimed identify regulatory microRNAs involved modulation femoral artery mice. Methods Results— Using microRNA-transcriptome analysis, we identified miR-155 as a downregulated microRNA during hindlimb ischemia. Correspondingly,...
Significance We discovered that the histone/protein deacetylase SIRT7, which is only member of mammalian sirtuin family residing primarily in nucleolus, stabilizes p53 response to UV-induced DNA damage by enabling binding deacetylated NPM MDM2/HDM2. The study unveils a crucial mechanism nucleolus controls cellular stress responses. Furthermore, it characterizes SIRT7 as potent regulator and offers opportunities manipulate levels, important for development antitumor therapies.
SIRT6 is a NAD+-dependent deacetylase that modulates chromatin structure and safeguards genomic stability. So far, has been assigned to the nucleus only nuclear targets of are known. Here, we demonstrate in response stress, C. elegans SIR-2.4 its mammalian orthologue localize cytoplasmic stress granules (SGs), interact with various SGs components induce their assembly. Loss or inhibition catalytic activity MEF cells impairs formation delays disassembly during recovery, while deficiency...
Abstract The NAD + -dependent SIRT1-7 family of protein deacetylases plays a vital role in various molecular pathways related to stress response, DNA repair, aging and metabolism. Increased activity individual sirtuins often exerts beneficial effects pathophysiological conditions whereas reduced is usually associated with disease conditions. Here, we demonstrate that SIRT6 deacetylates H3K56ac myofibers suppress expression utrophin, dystrophin-related stabilizing the sarcolemma absence...
Abstract Background Diet-induced obesity can result in the development of a diverse spectrum cardiovascular and metabolic diseases, including type 2 diabetes, dyslipidemia, non-alcoholic liver steatosis atherosclerotic disease. MicroRNAs have been described to be important regulators metabolism disease development. Methods In current study, we investigated effects ubiquitous miR-100 overexpression on weight gain phenotype newly generated transgenic mouse strain under normal chow high fat...
Systemic inflammation is a major feature of the post-cardiac arrest syndrome. The three monocyte subpopulations are thought to play an important role in this inflammatory state because they endowed with numerous pattern recognition receptors, such as CD14, that have been associated ischemia-reperfusion injury. By contrast, exaggerated antiinflammatory response has also described following cardiac arrest, which may be mediated by downregulation antigen presentation receptor HLA-DR. We report...
MicroRNAs are key regulators of the cardiac response to injury. MiR-100 has recently been suggested be involved in different forms heart failure, but functional studies lacking. In present study, we examined impact transgenic miR-100 overexpression on structure and function during physiological aging pathological pressure-overload-induced failure mice after transverse aortic constriction surgery. was moderately upregulated induction pressure overload mice. While our model...
Background Members of the mammalian sirtuin family, Sirt1 – Sirt7, are known to regulate metabolic processes especially carbohydrate and fat metabolism [1,2]. Sirt2 inhibit adipocyte differentiation [3,4] while Sirt6 prevent liver steatosis [5]. These examples illustrate a synergistic action different sirtuins in promoting lean, “healthy” phenotypes. We have previously shown that Sirt7 knockout mice display signs premature aging, suffer from progressive cardiomyopathy reduced lifespan [6]....
Objective: The accumulation of inflammatory leukocytes is a prerequisite adipose tissue inflammation during cardiometabolic disease. We previously reported that genetic deficiency the intracellular signaling adaptor TRAF5 (TNF [tumor necrosis factor] receptor–associated factor 5) accelerates atherosclerosis in mice by increasing cell recruitment. Here, we tested hypothesis an impairment modulates and its metabolic complications model diet-induced obesity mice. Approach Results: To induce...
Dedifferentiated vascular smooth muscle cells (vSMCs) play an essential role in neointima formation, and we now aim to investigate the of bone morphogenetic protein (BMP) modulator BMPER (BMP endothelial cell precursor-derived regulator) formation. To assess expression arterial restenosis, used a mouse carotid ligation model with perivascular cuff placement. Overall after vessel injury was increased; however, tunica media decreased compared untreated control. Consistently, proliferative,...
Vascular smooth muscle cells (VSMCs) play a key role in aortic aneurysm formation. Bone morphogenetic proteins (BMPs) have been implicated as important regulators of VSMC phenotype, and dysregulation the BMP pathway has shown to be associated with vascular diseases. The aim this study was investigate for first time effects BMP-4 on phenotype understand its development thoracic aneurysms (TAAs). Using angiotensin II (AngII) osmotic pump model mice, aortas from mice VSMC-specific deficiency...