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Phospholipase C gene expression, protein content, and activities in cardiac hypertrophy and heart failure due to

Melissa R Dent1, Naranjan S Dhalla, Paramjit S Tappia

  • 1Department of Physiology, Faculty of Medicine, St Boniface General Hospital Research Centre University of Manitoba, Winnipeg, Manitoba R2H 2A6, Canada.

American Journal of Physiology. Heart and Circulatory Physiology
|April 10, 2004
PubMed

Insights

Volume overload from arteriovenous shunts causes cardiac hypertrophy and heart failure. Phosphoinositide phospholipase C (PLC) isozyme activity changes, impacting cardiac function during these conditions.

Area of Science:

  • Cardiovascular Physiology
  • Molecular Cardiology
  • Biochemistry

Background:

  • Volume overload from arteriovenous (AV) shunts induces cardiac hypertrophy and can progress to heart failure.
  • Phosphoinositide phospholipase C (PLC) enzymes play a role in cardiac function by metabolizing phosphatidylinositol 4,5-bisphosphate (PIP(2)).

Purpose of the Study:

  • To investigate the dynamic changes in diacylglycerol (DAG) and inositol (1,4,5)-trisphosphate (IP(3)) levels.
  • To analyze the time-course of alterations in phosphoinositide phospholipase C (PLC) isozyme gene expression, protein content, and enzymatic activity.
  • To correlate these molecular changes with cardiac hypertrophy and heart failure induced by AV shunt in a rat model.

Main Methods:

  • Induction of volume overload using an AV shunt in Sprague-Dawley rats.
  • Measurement of left ventricle (LV)-to-body weight ratio to confirm cardiac hypertrophy.
  • Quantification of PLC isozyme (beta(1), gamma(1), delta(1)) mRNA, protein levels, and enzymatic activities at various time points.
  • Assessment of sarcolemmal (SL) PIP(2) content.

Main Results:

  • Cardiac hypertrophy was confirmed by increased LV-to-body weight ratio at 4 weeks.
  • PLC-beta(1) activity, mRNA, and protein increased early (3 days to 2 weeks) but normalized by 4 weeks, then increased again at later time points (8-16 weeks).
  • PLC-gamma(1) activity, mRNA, and protein increased at 3 days and 4 weeks, while PLC-delta(1) activity, gene expression, and protein decreased progressively from 1 to 4 weeks, with further depression at 8-16 weeks.
  • Sarcolemmal PIP(2) content progressively decreased during hypertrophy and heart failure.

Conclusions:

  • Phosphoinositide phospholipase C (PLC) isozyme signaling is upregulated during the development of cardiac hypertrophy.
  • PLC isozyme signaling is altered, with decreased activity of certain isoforms, in the progression to heart failure due to volume overload.
  • These findings highlight the complex role of PLC isozymes in the pathophysiology of pressure overload-induced cardiac remodeling and dysfunction.

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