Schmederer, Z, Rolim, N, Scott Bowen, T et al. (3 more authors) (2018) Endothelial function is disturbed in a hypertensive diabetic animal model of HFpEF: Moderate continuous vs. high intensity interval training. International Journal of Cardiology, 273. pp. 147-154. ISSN 0167-5273
Abstract
Background: Heart failure with preserved ejection fraction (HFpEF) is associated with endothelial dysfunction, but the molecular mechanisms still remain unclear. Whether exercise training (ET) along with which optimal modality can improve endothelial function is controversial. The present study used a hypertensive, diabetic-driven HFpEF animal model (ZSF1 rats) to determine whether different training modalities (moderate-continuous (MCT) and high-intensity interval training (HIIT)) could reverse endothelial dysfunction and to understand the underlying molecular mechanisms. Methods and results: The development of HFpEF in ZSF1 obese animals was confirmed by echocardiography and hemodynamic measurements. Thereafter, animals were randomized into following groups: 1) sedentary, 2) 8 weeks of MCT, 3) 8 weeks of HIIT. ZSF1 lean animals served as control. In vitro measurement of endothelial function in aortic rings revealed significantly impaired endothelial-dependent and -independent vasodilation in HFpEF, which was reversed by MCT and HIIT. At the molecular level, the development of endothelial dysfunction was associated with a reduced expression / activation of endothelial nitric oxide synthase (eNOS), an increase in NADPH and activation of c-Jun N-terminal protein kinase (JNK), a reduced collagen I/III ratio and a reduced lining of the vessel wall by endothelial cells. ET primarily decreased NADPH oxidase expression, and JNK activation, elevated collagen I/III ratio while further improving aortic endothelial cell coverage. Conclusions: The present study provides evidence that endothelial dysfunction occurs in experimental HFpEF and that ET, independent of the studied training modality, reverses endothelial dysfunction and specific molecular alterations. ET may therefore provide an important therapeutic intervention for HFpEF patients.
Metadata
Item Type: | Article |
---|---|
Authors/Creators: |
|
Copyright, Publisher and Additional Information: | © 2018 Elsevier B.V. This is an author produced version of a paper published in International Journal of Cardiology. Uploaded in accordance with the publisher's self-archiving policy. |
Dates: |
|
Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Biomedical Sciences (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 28 Sep 2018 09:28 |
Last Modified: | 30 Aug 2019 00:42 |
Status: | Published |
Publisher: | Elsevier |
Identification Number: | 10.1016/j.ijcard.2018.08.087 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:136327 |