The University of Toledo Translation Journal of Medical Sciences 
 Cardiology Abstract, Department of Medicine Research Symposium UTJMS 2023 May 05; 11(1):e1-e2 

Paraoxanase 1 Deletion Leads to Increased 
Cardiac Remodeling and Cardiac Fibrosis 
in a Dahl Salt-Sensitive Rat Model of 
Chronic Kidney Disease 
Sophia Soehnlen1*, Prabhatchandra Dube1, Fatimah K. Khalaf1, Chrysan J. 
Mohammed1, Armelle DeRiso1, Dhanushya Battepati1, Tiana Sarsour1, Iman 
Tassavvor1, Andrew L. Kleinhenz1, Steven T. Haller, PhD1, Eric E. Morgan1, David 
J. Kennedy, PhD1

1Division of Cardiology, Department of Medicine, The University of Toledo, Toledo, 

OH 43614 

*Corresponding author: Sophia.Soehnlen@rockets.utoledo.edu

Published: 05 May 2023 

Introduction: Paraoxanase 1 (Pon-1) synthesis occurs in liver and circulates bound to high-density 
lipoproteins (HDL), contributing to HDL’s antioxidant, anti-inflammatory and anti-atherogenic 
properties. Decreased circulating Pon-1 activity is associated with increased oxidant stress and adverse 
clinical outcomes in the setting of chronic kidney disease (CKD). Whether decreased Pon-1 is 
mechanistically linked to adverse cardiovascular outcomes in CKD, however, remains unclear.  We 
tested the hypothesis that Pon-1 is cardioprotective in a Dahl salt-sensitive model of hypertensive renal 
disease. 

Methods: Ten-week-old, age-matched male and female control Dahl salt-sensitive rats (SS) and Pon1 
mutant rats (SS-Pon1 KO) were maintained on high salt diet (8% NaCl) for up to 12 weeks to initiate 
salt-sensitive hypertensive renal disease. Left ventricular geometry and function were assessed in male 
SS and SS-Pon1 KO rats at the end of week four of high salt diet via echocardiography and animals 
were euthanized and hearts processed for histology.   

Results: SS-Pon1 KO male rats demonstrated a significantly increased relative cardiac wall thickness 
(0.77+/-0.05 vs. 0.58+/-0.02) and fractional shortening (0.62+/-0.02 vs. 0.53+/-0.01), as well as 
significantly increased mean velocity of circumferential fiber shortening (circ/s, 6.37+/-0.33 vs. 5.52+/-
0.17) and cardiac index (ml/min/kg, 184+/-18 vs. 136+/-11) vs age matched SS rats. No difference in 
heart rates was observed. Upon histological examination, heart sections of SS-Pon1 KO male rats 
showed a significant increase in fibrosis and heart-weight-to-body-weight ratio compared to the age 
matched SS rats.  

https://dx.doi.org/10.46570/utjms.vol11-2023-645 

https://dx.doi.org/10.46570/utjms.vol11-2023-645
mailto:Sophia.Soehnlen@rockets.utoledo.edu


https://dx.doi.org/10.46570/utjms.vol11-2023-645 UTJMS 11(1):e1-e2 

https://dx.doi.org/10.46570/utjms.vol11-2023-645 2 ©2023 UTJMS 

Conclusion:  Our findings suggest that loss of PON-1 in salt-sensitive hypertensive rats leads to a 
cardiac phenotype consistent with compensated heart failure. 

https://dx.doi.org/10.46570/utjms.vol11-2023-645
https://dx.doi.org/10.46570/utjms.vol11-2023-645