1,8-Cineole ameliorates right ventricle dysfunction associated with pulmonary arterial hypertension by restoring connexin43 and mitochondrial homeostasis.

Abstract

For the first time, the present study unravels a cardiospecific therapeutic approach for Pulmonary Arterial Hypertension (PAH), a disease with a very poor prognosis and high mortality rates due to right ventricle (RV) dysfunction. We first established a new in vitro model of high-pressure-induced hypertrophy that closely resembles heart defects associated with PAH and validated our in vitro findings on a preclinical in vivo model of monocrotaline (MCT)-induced PAH. Our results showed the in vitro antihypertrophic effect of 1,8-cineole, a monoterpene widely found in several essential oils. Also, a decrease in RV hypertrophy and fibrosis, and an improvement in heart function in vivo was observed, when 1,8-cineole was applied topically. Furthermore, 1,8-cineole restored gap junction protein connexin43 distribution at the intercalated disks and mitochondrial functionality, suggesting it may act by preserving cardiac cell-to-cell communication and bioenergetics. Overall, our results point out a promising therapeutic compound that can be easily applied topically, thus paving the way for the development of effective cardiac-specific therapies to greatly improve PAH outcomes.

• Authors: Jorge M Alves-Silva, Mónica Zuzarte, Carla Marques, Sofia Viana, Inês Preguiça, Rui Baptista, Cátia Ferreira, Carlos Cavaleiro, Neuza Domingues, Vilma A Sardão, Paulo J Oliveira, Flávio Reis, Lígia Salgueiro, Henrique Girão
• Journal: Pharmacological research (Pharmacol Res) Vol. 180 Pg. 106151 (06 2022) ISSN: 1096-1186 [Electronic] Netherlands
• PMID: 35247601 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 Elsevier Ltd. All rights reserved.

Chemical References

• Connexin 43
• Eucalyptol

Topics

• Animals
• Cardiomyopathies
• Connexin 43
• Disease Models, Animal
• Eucalyptol (therapeutic use)
• Heart Ventricles (metabolism)
• Homeostasis
• Humans
• Hypertension, Pulmonary (drug therapy)
• Hypertrophy, Right Ventricular (metabolism)
• Pulmonary Arterial Hypertension (drug therapy)
• Ventricular Dysfunction, Right (metabolism)