Cardioprotective Role for Paraoxonase-1 in Chronic Kidney Disease.

Autor:	Dube P; Department of Medicine, College of Medicine and Life Sciences, University of Toledo, Toledo, OH 43606, USA., Khalaf FK; Department of Medicine, College of Medicine and Life Sciences, University of Toledo, Toledo, OH 43606, USA.; Department of Clinical Pharmacy, University of Alkafeel, Najaf 54001, Iraq., DeRiso A; Department of Medicine, College of Medicine and Life Sciences, University of Toledo, Toledo, OH 43606, USA., Mohammed CJ; Department of Medicine, College of Medicine and Life Sciences, University of Toledo, Toledo, OH 43606, USA., Connolly JA; Department of Medicine, College of Medicine and Life Sciences, University of Toledo, Toledo, OH 43606, USA., Battepati D; Department of Medicine, College of Medicine and Life Sciences, University of Toledo, Toledo, OH 43606, USA., Lad A; Department of Medicine, College of Medicine and Life Sciences, University of Toledo, Toledo, OH 43606, USA., Breidenbach JD; Department of Medicine, College of Medicine and Life Sciences, University of Toledo, Toledo, OH 43606, USA., Kleinhenz AL; Department of Medicine, College of Medicine and Life Sciences, University of Toledo, Toledo, OH 43606, USA., Khatib-Shahidi B; Department of Medicine, College of Medicine and Life Sciences, University of Toledo, Toledo, OH 43606, USA., Patel M; Department of Medicine, College of Medicine and Life Sciences, University of Toledo, Toledo, OH 43606, USA., Tassavvor I; Department of Medicine, College of Medicine and Life Sciences, University of Toledo, Toledo, OH 43606, USA., Gohara AF; Department of Medicine, College of Medicine and Life Sciences, University of Toledo, Toledo, OH 43606, USA., Malhotra D; Department of Medicine, College of Medicine and Life Sciences, University of Toledo, Toledo, OH 43606, USA., Morgan EE; Department of Surgery, University of Toledo College of Medicine and Life Sciences, Toledo, OH 43606, USA., Haller ST; Department of Medicine, College of Medicine and Life Sciences, University of Toledo, Toledo, OH 43606, USA., Kennedy DJ; Department of Medicine, College of Medicine and Life Sciences, University of Toledo, Toledo, OH 43606, USA.
Jazyk:	angličtina
Zdroj:	Biomedicines [Biomedicines] 2022 Sep 16; Vol. 10 (9). Date of Electronic Publication: 2022 Sep 16.
DOI:	10.3390/biomedicines10092301
Abstrakt:	Paraoxonase-1 (PON-1) is a hydrolytic enzyme associated with HDL, contributing to its anti-inflammatory, antioxidant, and anti-atherogenic properties. Deficiencies in PON-1 activity result in oxidative stress and detrimental clinical outcomes in the context of chronic kidney disease (CKD). However, it is unclear if a decrease in PON-1 activity is mechanistically linked to adverse cardiovascular events in CKD. We investigated the hypothesis that PON-1 is cardioprotective in a Dahl salt-sensitive model of hypertensive renal disease. Experiments were performed on control Dahl salt-sensitive rats (SS Mcwi , hereafter designated SS-WT rats) and mutant PON-1 rats (SS-Pon1 em1Mcwi , hereafter designated SS-PON-1 KO rats) generated using CRISPR gene editing technology. Age-matched 10-week-old SS and SS-PON-1 KO male rats were maintained on high-salt diets (8% NaCl) for five weeks to induce hypertensive renal disease. Echocardiography showed that SS-PON-1 KO rats but not SS-WT rats developed compensated left ventricular hypertrophy after only 4 weeks on the high-salt diet. RT-PCR analysis demonstrated a significant increase in the expression of genes linked to cardiac hypertrophy, inflammation, and fibrosis, as well as a significant decrease in genes essential to left ventricular function in SS-PON-1 KO rats compared to SS-WT rats. A histological examination also revealed a significant increase in cardiac fibrosis and immune cell infiltration in SS-PON-1 KO rats, consistent with their cardiac hypertrophy phenotype. Our data suggest that a loss of PON-1 in the salt-sensitive hypertensive model of CKD leads to increased cardiac inflammation and fibrosis as well as a molecular and functional cardiac phenotype consistent with compensated left ventricular hypertrophy.
Databáze:	MEDLINE
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