Saxagliptin Prevents Increased Coronary Vascular Stiffness in Aortic-Banded Mini Swine
| Autor: | Melissa S. Cobb, Craig A. Emter, Gianmaria Minervini, An Ouyang, T. Dylan Olver, Bradley S. Fleenor, Jessica A. Hiemstra |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty animal structures Swine Adipose tissue Adamantane Aorta Thoracic 030204 cardiovascular system & hematology 03 medical and health sciences chemistry.chemical_compound Vascular Stiffness 0302 clinical medicine Internal medicine Internal Medicine medicine Animals Ligation Heart Failure Dipeptidyl-Peptidase IV Inhibitors Ejection fraction Ventricular Remodeling business.industry Nitrotyrosine Stroke Volume Dipeptides medicine.disease Coronary Vessels Coronary arteries Disease Models Animal 030104 developmental biology medicine.anatomical_structure chemistry Heart failure Cardiology Swine Miniature Advanced glycation end-product Aortic stiffness business Artery |
| Zdroj: | Hypertension. 72:466-475 |
| ISSN: | 1524-4563 0194-911X |
| Popis: | Increased peripheral conduit artery stiffness has been shown in patients with heart failure (HF) with preserved ejection fraction. However, it is unknown whether this phenomenon extends to the coronary vasculature. HF with preserved ejection fraction may be driven, in part, by coronary inflammation, and inhibition of the enzyme DPP-4 (dipeptidyl-peptidase 4) reduces inflammation and oxidative stress. The purpose of this study was to determine the effect of saxagliptin—a DPP-4 inhibitor—on coronary stiffness in aortic-banded mini swine. We hypothesized saxagliptin would prevent increased coronary artery stiffness in a translational swine model with cardiac features of HF with preserved ejection fraction by inhibiting perivascular adipose tissue inflammation. Yucatan mini swine were divided into 3 groups: control, aortic-banded untreated HF, and aortic-banded saxagliptin-treated HF. Ex vivo mechanical testing was performed on the left circumflex and right coronary arteries, and advanced glycation end product, NF-κB (nuclear factor-κB), and nitrotyrosine levels were measured. An increase in the coronary elastic modulus of HF animals was associated with increased vascular advanced glycation end products, NF-κB, and nitrotyrosine levels compared with control and prevented by saxagliptin treatment. Aortas from healthy mice were treated with media from swine perivascular adipose tissue culture to assess its role on vascular stiffening. Conditioned media from HF and saxagliptin-treated HF animals increased mouse aortic stiffness; however, only perivascular adipose tissue from the HF group showed increased advanced glycation end products and NF-κB levels. In conclusion, our data show increased coronary conduit vascular stiffness was prevented by saxagliptin and associated with decreased advanced glycation end products, NF-κB, and nitrotyrosine levels in a swine model with potential relevance to HF with preserved ejection fraction. |
| Databáze: | OpenAIRE |
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