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Global PIEZO1 Gain-of-Function Mutation Causes Cardiac Hypertrophy and Fibrosis in Mice
Fiona Bartoli1, Elizabeth L Evans1, Nicola M Blythe1
1Leeds Institute of Cardiovascular and Metabolic Medicine, School of Medicine, University of Leeds, Leeds LS2 9JT, UK.
Cells
|April 12, 2022
Summary
Gain-of-function mutations in PIEZO1 channels, linked to anemia, also cause heart problems. This study shows PIEZO1 overactivity leads to cardiac hypertrophy and fibrosis in mice, impacting heart health.
Area of Science:
- Cardiovascular Biology
- Ion Channel Physiology
- Cellular Mechanotransduction
Background:
- PIEZO1 forms mechanically-activated cation channels.
- Gain-of-function PIEZO1 mutations cause dehydrated hereditary stomatocytosis (DHS), a form of anemia.
- The role of PIEZO1 in cardiac function is not well understood.
Purpose of the Study:
- To investigate the effects of PIEZO1 gain-of-function mutations on cardiac structure and function.
- To explore the mechanisms underlying PIEZO1-mediated cardiac pathology.
Main Methods:
- Mice with the PIEZO1 M2241R mutation (mimicking DHS) were studied.
- Cardiac mass, interventricular septum thickness, and myocyte size were measured.
- Gene expression related to cardiac hypertrophy and fibrosis was analyzed.
- Cardiac fibroblast responses to PIEZO1 agonism were assessed.
Main Results:
- Mice with the PIEZO1 mutation exhibited increased cardiac mass and interventricular septum thickness.
- Myocyte size was enlarged, with increased expression of hypertrophy-associated genes (Anp, Acta1, β-MHC).
- Cardiac fibrosis was evident, indicated by increased Col3a1 expression and enhanced fibroblast responses to PIEZO1 activation.
Conclusions:
- Excessive PIEZO1 activity, as seen in DHS mutations, detrimentally affects the heart.
- PIEZO1-mediated cardiac hypertrophy and fibrosis are significant consequences.
- Amplified PIEZO1 function in cardiac fibroblasts contributes to these detrimental cardiac effects.
