CSRP3 mediates polyphenols-induced cardioprotection in hypertension.

Abstract

Berries contain bioactive polyphenols, whose capacity to prevent cardiovascular diseases has been established recently in animal models as well in human clinical trials. However, cellular processes and molecular targets of berries polyphenols remain to be identified. The capacity of a polyphenol-enriched diet (i.e., blueberries, blackberries, raspberries, strawberry tree fruits and Portuguese crowberries berries mixture) to promote animal survival and protect cardiovascular function from salt-induced hypertension was evaluated in a chronic salt-sensitive Dahl rat model. The daily consumption of berries improved survival of Dahl/salt-sensitive rats submitted to high-salt diet and normalized their body weight, renal function and blood pressure. In addition, a prophylactic effect was observed at the level of cardiac hypertrophy and dysfunction, tissue cohesion and cardiomyocyte hypertrophy. Berries also protected the aorta from fibrosis and modulated the expression of aquaporin-1, a channel involved in endothelial water and nitric oxide permeability. Left ventricle proteomics analysis led to the identification of berries and salt metabolites targets, including cystein and glycin-rich protein 3 (CSRP3), a protein involved in myocyte cytoarchitecture. In neonatal rat ventricular cardiomyocytes, CSRP3 was validated as a target of a berries-derived polyphenol metabolite, 4-methylcatechol sulfate, at micromolar concentrations, mimicking physiological conditions of human plasma circulation. Accordingly, siRNA silencing of CSRP3 and 4-methylcatechol sulfate pretreatment reversed cardiomyocyte hypertrophy and CSRP3 overexpression induced by phenylephrine. Our systemic study clearly supports the modulation of CSRP3 by a polyphenol-rich berries diet as an efficient cardioprotective strategy in hypertension-induced heart failure.

• Authors: Carole Oudot, Andreia Gomes, Valérie Nicolas, Morgane Le Gall, Philippe Chaffey, Cédric Broussard, Giuseppe Calamita, Maria Mastrodonato, Patrizia Gena, Jean-Luc Perfettini, Jocelyne Hamelin, Antoinette Lemoine, Rodolphe Fischmeister, Helena L A Vieira, Claudia N Santos, Catherine Brenner
• Journal: The Journal of nutritional biochemistry (J Nutr Biochem) Vol. 66 Pg. 29-42 (04 2019) ISSN: 1873-4847 [Electronic] United States
• PMID: 30703746 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Elsevier Inc. All rights reserved.

Chemical References

• Cardiotonic Agents
• LIM Domain Proteins
• Muscle Proteins
• Polyphenols
• cysteine and glycine-rich protein 3

Topics

• Animals
• Cardiomegaly (diet therapy, prevention & control)
• Cardiotonic Agents (pharmacology)
• Cells, Cultured
• Disease Models, Animal
• Fruit
• Heart (drug effects)
• Hypertension (diet therapy, mortality)
• LIM Domain Proteins (genetics, metabolism)
• Male
• Muscle Proteins (genetics, metabolism)
• Myocytes, Cardiac (drug effects, metabolism, pathology)
• Polyphenols (pharmacology)
• Rats, Inbred Dahl