Abstract
| Original language | English |
|---|---|
| Pages (from-to) | e005596 |
| Journal | Circulation. Heart failure |
| Volume | 12 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - 2019 |
| Externally published | Yes |
Cite this
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Arterial Remodeling and Dysfunction in the ZSF1 Rat Model of Heart Failure With Preserved Ejection Fraction. / Leite, Sara; Cerqueira, Rui J.; Ibarrola, Jaime; Fontoura, Dulce; Fernández-Celis, Amaya; Zannad, Faiez; Falcão-Pires, Inês; Paulus, Walter J.; Leite-Moreira, Adelino F.; Rossignol, Patrick; López-Andrés, Natalia; Lourenço, André P.
In: Circulation. Heart failure, Vol. 12, No. 7, 2019, p. e005596.Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - Arterial Remodeling and Dysfunction in the ZSF1 Rat Model of Heart Failure With Preserved Ejection Fraction
AU - Leite, Sara
AU - Cerqueira, Rui J.
AU - Ibarrola, Jaime
AU - Fontoura, Dulce
AU - Fernández-Celis, Amaya
AU - Zannad, Faiez
AU - Falcão-Pires, Inês
AU - Paulus, Walter J.
AU - Leite-Moreira, Adelino F.
AU - Rossignol, Patrick
AU - López-Andrés, Natalia
AU - Lourenço, André P.
PY - 2019
Y1 - 2019
N2 - BACKGROUND: The interplay between the stiffened heart and vessels has long been viewed as a core mechanism in heart failure with preserved ejection fraction, but the incremental vascular molecular remodeling mechanisms from systemic arterial hypertension to heart failure with preserved ejection fraction remain poorly investigated. Our aim was to characterize central arterial remodeling and dysfunction in ZSF1 obese rats and to compare it with hypertensive ZSF1 lean and healthy Wistar-Kyoto controls. METHODS AND RESULTS: Twenty-week-old male ZSF1 obese (n=9), lean (n=9), and Wistar-Kyoto rats (n=9) underwent left ventricular pressure-volume loop evaluation and synchronous acquisition of ascending aortic flow and pressure. Aortic rings underwent functional evaluation, histology, and molecular biology studies. Although mean arterial pressure, characteristic aortic impedance, and reactivity to phenylephrine were similarly increased in hypertensive ZSF1 lean and obese, only ZSF1 obese showed impaired relaxation and upward-shifted end-diastolic pressure-volume relationships despite preserved systolic function indexes, denoting heart failure with preserved ejection fraction. ZSF1 obese phenotype further showed decreased aortic compliance, increased wave reflection, and impaired direct NO donor and endothelial-mediated vasodilation which were accompanied on structural and molecular grounds by aortic media thickening, higher collagen content and collagen/elastin ratio, increased fibronectin and α-5 integrin protein expression and upregulated TGF (transforming growth factor)-β and CTGF (connective tissue growth factor) levels. CONCLUSIONS: Functional, molecular, and structural disturbances of central vessels and their potentially underlying pathways were newly characterized in experimental heart failure with preserved ejection fraction rendering the ZSF1 obese rat model suitable for preclinical testing.
AB - BACKGROUND: The interplay between the stiffened heart and vessels has long been viewed as a core mechanism in heart failure with preserved ejection fraction, but the incremental vascular molecular remodeling mechanisms from systemic arterial hypertension to heart failure with preserved ejection fraction remain poorly investigated. Our aim was to characterize central arterial remodeling and dysfunction in ZSF1 obese rats and to compare it with hypertensive ZSF1 lean and healthy Wistar-Kyoto controls. METHODS AND RESULTS: Twenty-week-old male ZSF1 obese (n=9), lean (n=9), and Wistar-Kyoto rats (n=9) underwent left ventricular pressure-volume loop evaluation and synchronous acquisition of ascending aortic flow and pressure. Aortic rings underwent functional evaluation, histology, and molecular biology studies. Although mean arterial pressure, characteristic aortic impedance, and reactivity to phenylephrine were similarly increased in hypertensive ZSF1 lean and obese, only ZSF1 obese showed impaired relaxation and upward-shifted end-diastolic pressure-volume relationships despite preserved systolic function indexes, denoting heart failure with preserved ejection fraction. ZSF1 obese phenotype further showed decreased aortic compliance, increased wave reflection, and impaired direct NO donor and endothelial-mediated vasodilation which were accompanied on structural and molecular grounds by aortic media thickening, higher collagen content and collagen/elastin ratio, increased fibronectin and α-5 integrin protein expression and upregulated TGF (transforming growth factor)-β and CTGF (connective tissue growth factor) levels. CONCLUSIONS: Functional, molecular, and structural disturbances of central vessels and their potentially underlying pathways were newly characterized in experimental heart failure with preserved ejection fraction rendering the ZSF1 obese rat model suitable for preclinical testing.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85072260256&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/31525070
U2 - 10.1161/CIRCHEARTFAILURE.118.005596
DO - 10.1161/CIRCHEARTFAILURE.118.005596
M3 - Article
VL - 12
SP - e005596
JO - Circulation. Heart failure
JF - Circulation. Heart failure
SN - 1941-3289
IS - 7
ER -