TY  - JOUR
A1  - Hoffmann, Linda S.
A1  - Etzrodt, Jennifer
A1  - Willkomm, Lena
A1  - Sanyal, Abhishek
A1  - Scheja, Ludger
A1  - Fischer, Alexander W. C.
A1  - Stasch, Johannes-Peter
A1  - Bloch, Wilhelm
A1  - Friebe, Andreas
A1  - Heeren, Joerg
A1  - Pfeifer, Alexander
T1  - Stimulation of soluble guanylyl cyclase protects against obesity by recruiting brown adipose tissue
JF  - Nature Communications
N2  - Obesity is characterized by a positive energy balance and expansion of white adipose tissue (WAT). In contrast, brown adipose tissue (BAT) combusts energy to produce heat. Here we show that a small molecule stimulator (BAY 41-8543) of soluble guanylyl cyclase (sGC), which produces the second messenger cyclic GMP (cGMP), protects against diet-induced weight gain, induces weight loss in established obesity, and also improves the diabetic phenotype. Mechanistically, the haeme-dependent sGC stimulator BAY 41-8543 enhances lipid uptake into BAT and increases whole-body energy expenditure, whereas ablation of the haeme-containing \(\beta\)\(_{1}\)-subunit of sGC severely impairs BAT function. Notably, the sGC stimulator enhances differentiation of human brown adipocytes as well as induces 'browning' of primary white adipocytes. Taken together, our data suggest that sGC is a potential pharmacological target for the treatment of obesity and its comorbidities.
KW  - decompensated heart failure
KW  - mitochondrial biogenesis
KW  - pulmonary hypertension
KW  - nitric oxide
KW  - erectile dysfunction
KW  - beige adipocytes
KW  - fat development
KW  - cGMP
KW  - riociguat
KW  - white
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-143127
VL  - 6
IS  - 7235
ER  - 
TY  - JOUR
A1  - Korkmaz, Yüksel
A1  - Puladi, Behrus
A1  - Galler, Kerstin
A1  - Kämmerer, Peer W.
A1  - Schröder, Agnes
A1  - Gölz, Lina
A1  - Sparwasser, Tim
A1  - Bloch, Wilhelm
A1  - Friebe, Andreas
A1  - Deschner, James
T1  - Inflammation in the human periodontium induces downregulation of the α\(_1\)- and β\(_1\)-subunits of the sGC in cementoclasts
JF  - International Journal of Molecular Sciences
N2  - Nitric oxide (NO) binds to soluble guanylyl cyclase (sGC), activates it in a reduced oxidized heme iron state, and generates cyclic Guanosine Monophosphate (cGMP), which results in vasodilatation and inhibition of osteoclast activity. In inflammation, sGC is oxidized and becomes insensitive to NO. NO- and heme-independent activation of sGC requires protein expression of the α\(_1\)- and β\(_1\)-subunits. Inflammation of the periodontium induces the resorption of cementum by cementoclasts and the resorption of the alveolar bone by osteoclasts, which can lead to tooth loss. As the presence of sGC in cementoclasts is unknown, we investigated the α\(_1\)- and β\(_1\)-subunits of sGC in cementoclasts of healthy and inflamed human periodontium using double immunostaining for CD68 and cathepsin K and compared the findings with those of osteoclasts from the same sections. In comparison to cementoclasts in the healthy periodontium, cementoclasts under inflammatory conditions showed a decreased staining intensity for both α\(_1\)- and β\(_1\)-subunits of sGC, indicating reduced protein expression of these subunits. Therefore, pharmacological activation of sGC in inflamed periodontal tissues in an NO- and heme-independent manner could be considered as a new treatment strategy to inhibit cementum resorption.
KW  - nitric oxide
KW  - soluble guanylyl cyclase
KW  - cGMP
KW  - cementoclasts
KW  - cementum
KW  - osteoclasts
KW  - alveolar bone
KW  - periodontitis
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-285783
SN  - 1422-0067
VL  - 22
IS  - 2
ER  - 
TY  - JOUR
A1  - Koerdt, Steffen
A1  - Siebers, Joerg
A1  - Bloch, Wilhelm
A1  - Ristow, Oliver
A1  - Kuebler, Alexander C.
A1  - Reuther, Tobias
T1  - Immunohistochemial study on the expression of von Willebrand factor (vWF) after onlay autogenous iliac grafts for lateral alveolar ridge augmentation
N2  - Introduction

The main problems of autogenous bone transplants are their unpredictable atrophy and their loss of structure. One key factor lies in the poor revascularization of simple onlay grafts. The the aim of this study was to evaluate the revascularization processes in autogenous bone grafts from the iliac crest to the alveolar ridge.

Methods

In a sheep model, autogenous bone grafts were harvested from the iliac crest. A combination of a resorbable collagen membrane (CM) and deproteinized bovine bone material (DBBM) was used to modify the bone graft (experiment 2). This was compared with a simple onlay bone graft (control group, experiment 1). The amount of vessels in bone and connective tissue (CT), and the amount of CT were analyzed. The expression of von Willebrand factor (vWF) was compared between the two experimental groups using immunohistochemical analysis.

Results

The ratio of the amount of vessels in bone and CT changed over time, and more vessels could be detected in bone at 12–16 weeks of graft healing. The number of vessels were significantly higher in experiment 2 than in experiment 1. More CT was found in experiment 1, whereas the amount of CT in both experiments decreased over time.

Conclusion

This study shows a more intensive and extensive revascularization in experiment 2, as significantly more vessels were detected. The decreased amount of CT in experiment 2 clarifies its clinical superiority.
KW  - GBR
KW  - Collagen membrane
KW  - Revascularization
KW  - Connective tissue
KW  - Bone graft
KW  - vWF
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-110142
ER  -