Abstract | Introduction: Methods: For this experiment, we used Zucker Diabetic Fatty rats (fa/fa) and their age-matched lean controls (fa/+) that were treated with either vehicle or 20 mg/kg/day of Que for 6 weeks. Animals underwent echocardiographic (echo) examination before the first administration of Que and after 6 weeks. Results: After the initial echo examination, the diabetic rats showed increased E/A ratio, a marker of left ventricular ( LV) diastolic dysfunction, in comparison to the control group which was selectively reversed by Que. Following the echo analysis, Que reduced LV wall thickness and exhibited an opposite effect on LV luminal area. In support of these results, the total collagen content measured by hydroxyproline assay was decreased in the LVs of diabetic rats treated with Que. The follow-up immunoblot analysis of proteins conveying cardiac remodeling pathways revealed that Que was able to interfere with cardiac pro-hypertrophic signaling. In fact, Que reduced relative protein expression of pro-hypertrophic transcriptional factor MEF2 and its counter-regulator HDAC4 along with pSer246-HDAC4. Furthermore, Que showed potency to decrease GATA4 transcription factor, NFAT3 and calcineurin, as well as upstream extracellular signal-regulated kinase Erk5 which orchestrates several pro-hypertrophic pathways. Discussion: In summary, we showed for the first time that Que ameliorated pro-hypertrophic signaling on the level of epigenetic regulation and targeted specific upstream pathways which provoked inhibition of pro-hypertrophic signals in ZDF rats. Moreover, Que mitigated T2DM and obesity-induced diastolic dysfunction, therefore, might represent an interesting target for future research on novel cardioprotective agents.
|
Authors | Linda Bartosova, Csaba Horvath, Peter Galis, Kristina Ferenczyova, Barbora Kalocayova, Adrian Szobi, Adriana Duris-Adameova, Monika Bartekova, Tomas Rajtik |
Journal | Frontiers in endocrinology
(Front Endocrinol (Lausanne))
Vol. 13
Pg. 1029750
( 2022)
ISSN: 1664-2392 [Print] Switzerland |
PMID | 36568083
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Copyright | Copyright © 2022 Bartosova, Horvath, Galis, Ferenczyova, Kalocayova, Szobi, Duris-Adameova, Bartekova and Rajtik. |
Chemical References |
|
Topics |
- Rats
- Animals
- Quercetin
(pharmacology, therapeutic use)
- Diabetes Mellitus, Type 2
(complications, drug therapy, genetics)
- Diabetes Mellitus, Experimental
(complications, drug therapy, genetics)
- Epigenesis, Genetic
- Rats, Zucker
- Cardiomegaly
(genetics)
- Ventricular Dysfunction, Left
(complications)
- Obesity
(complications)
|