Pathological mechanism of heart failure with preserved ejection fraction in rats based on iTRAQ technology

Xu, Hang; Gao, Kai; Liu, Chao; Tian, Li; Ding, Yi; Ma, Jing

doi:10.7717/peerj.15280

Cited by 2 publications

(2 citation statements)

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“…In our study, canonical pathway analysis demonstrated inhibition of PPARα/RXRα, and upstream regulator analysis demonstrated significant inhibition of PGC-1α, PPARα, and PPARδ. A combination of gene and protein expression analysis reported abnormal PPAR signaling in a rodent model of HFpEF [21]. Abnormal PPAR signaling is extensively linked to abnormal substrate metabolism, reduced mitochondrial biogenesis, mitochondrial dysfunction, and energy deficiency in HF [20,21].…”

Section: Discussionmentioning

confidence: 99%

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Effect of Low-Level Tragus Stimulation on Cardiac Metabolism in Heart Failure with Preserved Ejection Fraction: A Transcriptomics-Based Analysis

Chakraborty,

Niewiadomska,

Farhat

et al. 2024

IJMS

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Abnormal cardiac metabolism precedes and contributes to structural changes in heart failure. Low-level tragus stimulation (LLTS) can attenuate structural remodeling in heart failure with preserved ejection fraction (HFpEF). The role of LLTS on cardiac metabolism is not known. Dahl salt-sensitive rats of 7 weeks of age were randomized into three groups: low salt (0.3% NaCl) diet (control group; n = 6), high salt diet (8% NaCl) with either LLTS (active group; n = 8), or sham stimulation (sham group; n = 5). Both active and sham groups received the high salt diet for 10 weeks with active LLTS or sham stimulation (20 Hz, 2 mA, 0.2 ms) for 30 min daily for the last 4 weeks. At the endpoint, left ventricular tissue was used for RNA sequencing and transcriptomic analysis. The Ingenuity Pathway Analysis tool (IPA) was used to identify canonical metabolic pathways and upstream regulators. Principal component analysis demonstrated overlapping expression of important metabolic genes between the LLTS, and control groups compared to the sham group. Canonical metabolic pathway analysis showed downregulation of the oxidative phosphorylation (Z-score: −4.707, control vs. sham) in HFpEF and LLTS improved the oxidative phosphorylation (Z-score = −2.309, active vs. sham). HFpEF was associated with the abnormalities of metabolic upstream regulators, including PPARGC1α, insulin receptor signaling, PPARα, PPARδ, PPARGC1β, the fatty acid transporter SLC27A2, and lysine-specific demethylase 5A (KDM5A). LLTS attenuated abnormal insulin receptor and KDM5A signaling. HFpEF is associated with abnormal cardiac metabolism. LLTS, by modulating the functioning of crucial upstream regulators, improves cardiac metabolism and mitochondrial oxidative phosphorylation.

show abstract

Section: Discussionmentioning

confidence: 99%

“…A combination of gene and protein expression analysis reported abnormal PPAR signaling in a rodent model of HFpEF [21]. Abnormal PPAR signaling is extensively linked to abnormal substrate metabolism, reduced mitochondrial biogenesis, mitochondrial dysfunction, and energy deficiency in HF [20,21].…”

Section: Discussionmentioning

confidence: 99%