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 Regulation of Cardiac 
Inflammation and Fibrosis in a Dahl Salt-
Sensitive Rat Model of Chronic Kidney 
Disease 
Ambika Sood, M21*, Meghana Ranabothu, M21, Amulya Marellapudi, M21, 
Prabhatchandra Dube, PhD1, Fatimah K. Khalaf1, Armelle DeRiso1, Chrysan J. 
Mohammed1, Dhanushya Battepati1, 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: Ambika.Sood@rockets.utoledo.edu

Published: 05 May 2023 

Objective: Paraoxonase-1 (PON1) is a lactonase enzyme associated with high-density liproteins (HDL), 
contributing to its antioxidant, anti-inflammatory and anti-atherogenic properties. Deficiencies in PON1 
result in oxidative stress and adverse clinical outcomes in chronic kidney disease (CKD), however the 
link to cardiovascular pathology in CKD is unknown. We investigated the hypothesis that PON1 is 
cardioprotective in a Dahl Salt-Sensitive model of hypertensive renal disease.   

Methods: Age matched 10-week-old Dahl salt-sensitive (SS) and mutant PON1 knock-out (SS-PON-1 
KO) male rats were maintained high salt diet (8% NaCl) for five weeks to induce hypertensive renal 
disease. Echocardiography was performed 1 week prior to euthanasia and hearts were processed for 
histopathologic and real-time (RT) PCR analysis of cardiac hypertrophy and fibrosis.   

Results: RT PCR analysis of cardiac left ventricular tissue revealed an increase in the expression of 
natriuretic peptide A (p< 0.0001) and myosin heavy chain 7 (p< 0.0001), suggesting cardiac hypertrophy 
in SS-PON-1 KO male rats compared to controls (SS). A decrease in sarcoplasmic/endoplasmic 
reticulum Ca2+ ATPase (p< 0.0001) expression was observed. CD68 staining showed an increase in 
macrophage infiltration in both perivascular (p< 0.0277) and interstitial (p< 0.005) regions within the 
heart sections of SS-PON-1 KO male rats. Furthermore, upregulation of tissue inhibitor of 
metalloproteases 1 (p< 0.0001) expression was seen.  

Results are consistent with the echocardiography analysis and trichrome analysis indicating increased 
cardiac fibrosis in SS-PON-1 KO vs SS rats.   

https://dx.doi.org/10.46570/utjms.vol11-2023-646 

https://dx.doi.org/10.46570/utjms.vol11-2023-646
mailto:Ambika.Sood@rockets.utoledo.edu


https://dx.doi.org/10.46570/utjms.vol11-2023-646 UTJMS 11(1):e1-e2 

https://dx.doi.org/10.46570/utjms.vol11-2023-646 2 ©2023 UTJMS 

Conclusion: Our findings indicate that loss of PON1 in salt-sensitive hypertensive rats results in 
compromised left ventricular function and hypertrophy, increased cardiac fibrosis and macrophage 
infiltration. 

https://dx.doi.org/10.46570/utjms.vol11-2023-646
https://dx.doi.org/10.46570/utjms.vol11-2023-646