Kidney Week

Abstract: FR-PO279

Cardiac Hypertrophy in Rodents With Polycystic Kidney Disease (PKD) Before the Onset of Hypertension

Session Information

• Genetic Diseases of the Kidneys: Cystic - II
  November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
  Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

• 1101 Genetic Diseases of the Kidneys: Cystic

Authors

• Oto, Ozgur Akin, Istanbul Universitesi Istanbul Tip Fakultesi, Istanbul, Istanbul, Turkey

Ozgur Akin Oto,

• Atwood, Daniel, University of Colorado Health, Aurora, Colorado, United States

Daniel Atwood,

• Chaudhary, Anjana, University of Colorado Health, Aurora, Colorado, United States

Anjana Chaudhary,

• Edelstein, Charles L., University of Colorado Health, Aurora, Colorado, United States

Charles L. Edelstein,

Background

The aim of the study was to determine whether there is cardiac hypertrophy (CH) before hypertension (HTN) in rodents and to further detail cardiac structure/ function in the heart in Pkd1^RC/RC (RC) mice.

Methods

12wk old PCK rats, a Pkhd1 gene model, and 120d RC mice, a hypomorphic Pkd1 gene model, were studied. A noninvasive tail-cuff system was used to measure BP. A Vevo 2100 was used for Echocardiography/ mitral Doppler measurements

Results

Heart weight/body weight (HW/BW) was increased in PCK rats at 12wks. HTN develops at 16wks in PCK rats. HW/BW was increased in RC mice before the onset of HTN (table). We previously described increased mTORC1/2/suppressed autophagy in the heart in 70d RC mice. mTORC1/ autophagy play a role in the CH, so we detailed cardiac structure/ function in RC mice. There was cardiac hypertrophy: increased intra-ventricular septum (IVS) and left ventricular wall (LVW) thickness. On echo there was increased LV mass, decreased ratio of peak velocity of early/ late filling of mitral inflow (grade 1 diastolic dysfunction) and decreased LV diastolic volume. Interestingly in 270dRC mice the cardiac dysfunction was different. There was severe Grade 4 diastolic dysfunction (increased E/A ratio) indicating restrictive filling of the LV. Normal ejection fraction fractional shortening indicated heart failure with preserved EF.

Conclusion

There was increased heart weight, CH, increased LV mass, grade 1 diastolic dysfunction, in RC mice before the onset of HTN. Factors other than HTN like increased mTORC1/2/ suppressed autophagy may contribute to causing CH in PKD mice.

*P<0.05, **P<0.01, ***P<0.001

Funding

• NIDDK Support