Intravenous and oral administration of the synthetic RNA drug, TY1, reverses heart failure with preserved ejection fraction in mice DOI Creative Commons

Kazutaka Miyamoto,

Xaviar Michael Jones,

Shukuro Yamaguchi

et al.

Basic Research in Cardiology, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 31, 2024

TY1, a synthetic non-coding RNA (ncRNA) bioinspired by small Y RNAs abundant in extracellular vesicles (EVs), decreases cGAS/STING activation myocardial infarction and thereby attenuates inflammation. Motivated the concept that heart failure with preserved ejection fraction (HFpEF) is systemic inflammatory disease, we tested TY1 murine model of HFpEF. Intravenous packaged transfection reagent, reversed cardiac manifestations HFpEF two-hit obese-hypertensive mice, without inducing weight loss. The effects were specific, insofar as they not reproduced control same nucleotide content but scrambled order. consistently suppressed stress-induced MAP kinase signaling, well downstream inflammatory, fibrotic, hypertrophic gene pathways tissue. only prevented actually key pathological processes underlying HFpEF, no evidence toxicity. Most noteworthy from practical perspective, intravenous feeding mice an oral micellar formulation TY1. As prototype for novel class ncRNA drugs which target cell stress, exhibits exceptional disease-modifying bioactivity

Language: Английский

Intravenous and oral administration of the synthetic RNA drug, TY1, reverses heart failure with preserved ejection fraction in mice DOI Creative Commons

Kazutaka Miyamoto,

Xaviar Michael Jones,

Shukuro Yamaguchi

et al.

Basic Research in Cardiology, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 31, 2024

TY1, a synthetic non-coding RNA (ncRNA) bioinspired by small Y RNAs abundant in extracellular vesicles (EVs), decreases cGAS/STING activation myocardial infarction and thereby attenuates inflammation. Motivated the concept that heart failure with preserved ejection fraction (HFpEF) is systemic inflammatory disease, we tested TY1 murine model of HFpEF. Intravenous packaged transfection reagent, reversed cardiac manifestations HFpEF two-hit obese-hypertensive mice, without inducing weight loss. The effects were specific, insofar as they not reproduced control same nucleotide content but scrambled order. consistently suppressed stress-induced MAP kinase signaling, well downstream inflammatory, fibrotic, hypertrophic gene pathways tissue. only prevented actually key pathological processes underlying HFpEF, no evidence toxicity. Most noteworthy from practical perspective, intravenous feeding mice an oral micellar formulation TY1. As prototype for novel class ncRNA drugs which target cell stress, exhibits exceptional disease-modifying bioactivity

Language: Английский

Citations

0