scholarly journals Arterial Stiffening in Western Diet-Fed Mice Is Associated with Increased Vascular Elastin, Transforming Growth Factor-β, and Plasma Neuraminidase

2016 ◽  
Vol 7 ◽  
Author(s):  
Christopher A. Foote ◽  
Jorge A. Castorena-Gonzalez ◽  
Francisco I. Ramirez-Perez ◽  
Guanghong Jia ◽  
Michael A. Hill ◽  
...  
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Western Diet ◽  
Arterial Stiffening ◽  
Vascular Elastin

scholarly journals Regional variation in arterial stiffening and dysfunction in Western diet-induced obesity

2015 ◽  
Vol 309 (4) ◽  
pp. H574-H582 ◽  
Author(s):  
Shawn B. Bender ◽  
Jorge A. Castorena-Gonzalez ◽  
Mona Garro ◽  
Constantino C. Reyes-Aldasoro ◽  
James R. Sowers ◽  
...  
Keyword(s):  
Coronary Arteries ◽  
Regional Variation ◽  
Transforming Growth Factor ◽  
Ex Vivo ◽  
Transforming Growth Factor Β ◽  
Western Diet ◽  
Internal Elastic Lamina ◽  
Arterial Stiffening ◽  
Femoral Arteries

Increased central vascular stiffening, assessed in vivo by determination of pulse wave velocity (PWV), is an independent predictor of cardiovascular event risk. Recent evidence demonstrates that accelerated aortic stiffening occurs in obesity; however, little is known regarding stiffening of other disease-relevant arteries or whether regional variation in arterial stiffening occurs in this setting. We addressed this gap in knowledge by assessing femoral PWV in vivo in conjunction with ex vivo analyses of femoral and coronary structure and function in a mouse model of Western diet (WD; high-fat/high-sugar)-induced obesity and insulin resistance. WD feeding resulted in increased femoral PWV in vivo. Ex vivo analysis of femoral arteries revealed a leftward shift in the strain-stress relationship, increased modulus of elasticity, and decreased compliance indicative of increased stiffness following WD feeding. Confocal and multiphoton fluorescence microscopy revealed increased femoral stiffness involving decreased elastin/collagen ratio in conjunction with increased femoral transforming growth factor-β (TGF-β) content in WD-fed mice. Further analysis of the femoral internal elastic lamina (IEL) revealed a significant reduction in the number and size of fenestrae with WD feeding. Coronary artery stiffness and structure was unchanged by WD feeding. Functionally, femoral, but not coronary, arteries exhibited endothelial dysfunction, whereas coronary arteries exhibited increased vasoconstrictor responsiveness not present in femoral arteries. Taken together, our data highlight important regional variations in the development of arterial stiffness and dysfunction associated with WD feeding. Furthermore, our results suggest TGF-β signaling and IEL fenestrae remodeling as potential contributors to femoral artery stiffening in obesity.

Perianale Fisteln bei CED: vom Mausmodell zur Klinik

2018 ◽  
Vol 75 (5) ◽  
pp. 287-294
Author(s):  
Michael Scharl
Keyword(s):  
Growth Factor ◽  
Morbus Crohn ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Interleukin 13

Zusammenfassung. Fisteln stellen nach wie vor eine der wichtigsten Komplikationen bei Patienten mit Morbus Crohn dar. Bei mindestens einem Drittel aller Morbus Crohn Patienten treten im Laufe der Erkrankung Fisteln auf. Eine dauerhafte Heilung der Fistel wird jedoch, auch unter Ausschöpfung sämtlicher medikamentöser und chirurgischer Therapieoptionen, nur in rund einem Drittel dieser Patienten erreicht. Der genaue molekulare Mechanismus der Fistelentstehung ist bis heute nicht ganz klar. Aus histopathologischer Sichtweise stellen Fisteln eine röhrenartige Struktur dar, welche von flachen epithelartigen Zellen ausgekleidet ist. Als ursächlicher Entstehungsmechanismus wird dabei die sogenannte epitheliale-zu-mesenchymale Transition (EMT) angesehen und es kann eine starke Expression der Entzündungsmediatoren Tumor Nekrose Faktor, Interleukin-13 und Transforming Growth Factor β in den Fistelarealen nachgewiesen werden. Zusätzlich zu den bereits etablierten, medikamentösen Therapieoptionen, also Antibiotika, Immunmodulatoren und anti-TNF Antikörper, stellt insbesondere der Einsatz der mesenchymalen Stammzelltherapie einen erfolgversprechenden Therapieansatz für die Zukunft dar.

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