Downregulation of right ventricular phosphodiesterase PDE-3A mRNA and protein before the development of canine heart failure

Cell Biochemistry and Biophysics
C J SmithT H Hintze

Abstract

Phosphodiesterase III (PDE-3) inhibitors are inotropes used to treat congestive heart failure (HF). Previous studies showed PDE-3A mRNA levels were reduced in the left ventricle (LV) in dogs subjected to pacing-induced HF. The present study evaluated a time-course for RV-specific changes in PDE-3A mRNAs and proteins after pacing for 3 wk (n = 4) or in HF (4-5 wk; n = 4-6). Total RNA from LV/RV tissues was isolated for Northern analyses; cytosolic and microsomal proteins were prepared for PDE-3A immunoblots. PDE-3A mRNAs (7-8 and 10 kb) were normalized against glyceraldehyde-3-phosphodehydrogenase (GAPDH) or ribosomal 18s with similar results. PDE-3A/GAPDH ratios in 3 wk were unchanged in LV, but significantly (p < 0.05) reduced by 48% in RV vs unpaced controls (n = 8). In contrast, PDE-3A (7-8 kb)/GAPDH ratios were significantly reduced in HF by 50-59% in both ventricles. Consistent with mRNA levels, significant reductions in microsomal 135 kDa (93-96%) and cytosolic 120 kDa PDE-3A (57-69%) were seen in both ventricles in HF or in the RV at 3 wk; an LV-specific reduction (50%) in cytosolic 80 kDa PDE-3A in HF was also detected. In summary, RV-specific downregulation of PDE-3A mRNA/protein(s) at 3 wk suggests that hemodynamic ra...Continue Reading

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Citations

May 2, 2002·The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation·Seema MitalThomas H Hintze
Sep 21, 2013·Future Medicinal Chemistry·Walter Knight, Chen Yan
Sep 8, 2004·Journal of Molecular and Cellular Cardiology·Rumi MasunagaMitsuyasu Itoh
Feb 19, 2002·Paediatric Anaesthesia·P D Booker
Mar 3, 2007·Circulation Research·Chen YanJun-ichi Abe
Apr 15, 2006·The Journal of Nervous and Mental Disease·Michael S Ritsner, Yael Ratner
Aug 2, 2001·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·H SenzakiD A Kass
Apr 5, 2003·American Journal of Physiology. Lung Cellular and Molecular Physiology·Siobhán B TarpeyMary I Townsley
Sep 29, 2000·American Journal of Physiology. Heart and Circulatory Physiology·M YanoM Matsuzaki
Jun 4, 2019·Journal of Molecular and Cellular Cardiology·Delphine MikaJérôme Leroy

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