RAAZ LAB

INTRODUCTION

Uwe Raaz’s research group at the Heart Research Center Göttingen focuses on the role of biomechanics and (epi-) genetics in the vascular aging process and in the development of cardiovascular diseases (such as heart failure, hypertension, stroke, or aneurysm formation). The group employs a wide interdisciplinary approach at the interface of molecular biology, medicine, mechanical engineering, chemistry, and bioinformatics. The ultimate goal of our research is to identify novel therapeutic targets and treatment options that are critically needed to reduce cardiovascular morbidity and mortality.

RESEARCH AREAS

Arterial stiffness

a major player driving cardiovascular disease

Arterial stiffness has long been recognized as a feature of arterial aging. Recently, arterial stiffness has received increasing attention in cardiovascular medicine, emerging as an independent risk factor for cardiovascular disease and mortality. Additionally, patients with highly prevalent metabolic disorders, such as diabetes mellitus, feature a dramatically increased cardiovascular risk coming along with accelerated arterial stiffening. As such, the group’s major interests are to delineate the molecular mechanisms leading to increased arterial stiffness and to better understand the pathomechanistic role of arterial stiffness in specific cardiovascular

diseases (such as atherosclerosis, aortic aneurysm/dissection, heart failure and stroke). As a result, we seek to define novel pharmaceutical targets to prevent arterial stiffening processes as well as develop strategies to reduce biomechanical stress arising from adverse vascular remodeling. As part of our functional studies we are employing in vivo vascular ultrasound methods, ex vivo material testing (pressure myography) as well as computer-based finite elements analysis (FEA).

Non-coding RNAs (ncRNAs )

promising therapeutical targets and biomarkers of cardiovascular disease

Non-coding RNAs (such as microRNAs, long non-coding RNAs) have recently attracted much attention not only as a novel class of gene and disease regulators but also as attractive targets for pharmaceutical intervention. In various projects the group is addressing the role of ncRNAs as mechanosensitive regulators of distinct vascular pathologies (such as aortic aneurysms, atherosclerosis, or age-related arterial stiffness).

Employing a comprehensive approach using human biobank materials as well as in vitro, in vivo and bioinformatical models we identify ncRNAs potentially involved in disease pathophysiology, taking advantage of latest profiling technologies (such as RNAseq). Subsequently, selected ncRNAs are subjected to rigorous mechanistic studies in vitro as well as in vivo to validate their utility as therapeutic targets.

Major collaborations

Philip S. Tsao (Divison of Cardiovascular Medicine, Stanford University School of Medicine, USA)
Ellen Kuhl (Department of Mechanical Engineering, Stanford University, USA)
Lars Maegdefessel (Technical University Munich, Germany/ Karolinska Institute Stockholm, Sweden)
Sebastian Kruss (Institute of Physical Chemistry, Göttingen, Germany)

SELECTED PUBLICATIONS

Lyle AN and Raaz U. Killing Me Unsoftly: Causes and Mechanisms of Arterial Stiffness.
Arteriosclerosis Thrombosis Vascular Biology. 2017;37:e1-e11.
Eken SM, Jin H, Chernogubova E, Li Y, Simon N, Sun C, Korzunowicz G, Busch A, Backlund A, Osterholm C, Razuvaev A, Renne T, Eckstein HH, Pelisek J, Eriksson P, Gonzalez Diez M, Perisic Matic L, Schellinger IN, Raaz U, Leeper NJ, Hansson GK, Paulsson-Berne G, Hedin U and Maegdefessel L. MicroRNA-210 Enhances Fibrous Cap Stability in Advanced Atherosclerotic Lesions.
Circulation Research 2017;120:633-644.
Riegler J, Tiburcy M, Ebert A, Tzatzalos E, Raaz U, Abilez OJ, Shen Q, Kooreman NG, Neofytou E, Chen VC, Wang M, Meyer T, Tsao PS, Connolly AJ, Couture LA, Gold JD, Zimmermann WH and Wu JC. Human Engineered Heart Muscles Engraft and Survive Long Term in a Rodent Myocardial Infarction Model.
Circulation Research 2015;117:720-30.
Raaz U, Schellinger IN, Chernogubova E, Warnecke C, Kayama Y, Penov K, Hennigs JK, Salomons F, Eken S, Emrich FC, Zheng WH, Adam M, Jagger A, Nakagami F, Toh R, Toyama K, Deng A, Buerke M, Maegdefessel L, Hasenfuss G, Spin JM and Tsao PS. Transcription Factor Runx2 Promotes Aortic Fibrosis and Stiffness in Type 2 Diabetes Mellitus.
Circulation Research 2015;117:513-24.
Raaz U, Zöllner AM, Schellinger IN, Toh R, Nakagami F, Brandt M, Emrich FC, Kayama Y, Eken SM, Adam M, Maedgefessel L, Hertel T, Deng A, Jagger A, Buerke M, Dalman RL, Spin JM, Kuhl E and Tsao PS. Segmental aortic stiffening contributes to experimental abdominal aortic aneurysm development.
Circulation. 2015;131:1783-95.
Maegdefessel L, Spin JM, Raaz U, Eken SM, Toh R, Azuma J, Adam M, Nagakami F, Heymann HM, Chernugobova E, Jin H, Roy J, Hultgren R, Caidahl K, Schrepfer S, Hamsten A, Eriksson P, McConnell MV, Dalman RL and Tsao PS. miR-24 limits aortic vascular inflammation and murine abdominal aneurysm development.
Nature communications. 2014;5:5214.
Raaz U, Toh R, Maegdefessel L, Adam M, Nakagami F, Emrich F, Spin J and Tsao P. Hemodynamic reglation of reactive oxygen species: implications of vascular diseases.
Antioxidants & Redox Signaling 2014;20:914-28.
Hong G, Lee JC, Robinson JT, Raaz U, Xie L, Huang NF, Cooke JP and Dai H. Multifunctional in vivo vascular imaging using near-infrared II fluorescence.
Nature Medicine 2012;18:1841-6.
Maegdefessel L, Azuma J, Toh R, Deng A, Merk D, Raiesdana A, Leeper N, Raaz U, Schoelmerich A, McConnell M, Dalman R, Spin J and Tsao P. MicroRNA-21 Blocks Abdominal Aortic Aneurysm Development and Nicotine-Augmented Expansion.
Science Translational Medicine 2012;4:122ra22.
Maegdefessel L, Azuma J, Toh R, Merk D, Deng A, Chin J, Raaz U, Schoelmerich A, Raiesdana A, Leeper N, McConnell M, Dalman R, Spin J and Tsao P. Inhibition of microRNA-29b reduces murine abdominal aortic aneurysm development.
Journal of Clincial Investigation 2012;122:497-506.