Mechanical Stretch Induces Hypertrophic Responses in Cardiac Myocytes of Angiotensin II Type 1a Receptor Knockout Mice
Population
Cultured cardiac myocytes of Angiotensin II type 1a receptor (AT1a) knockout (KO) mice and wild type (WT) mice
Comparison
Mechanical stretch with or without AT1… vs Unstretched myocytes and wild type (WT) myocytes
Design
Preclinical
Authors
Discussion
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Member takes
Implication
Stretch may induce cardiomyocyte hypertrophy via EGFR independently of AT1; leaves open clinical translation from this animal model.
Key Points
- This research aims to explore the role of angiotensin II type 1 receptor in mechanical stress-induced cardiac hypertrophy.
- Examined cardiac myocytes from AT1a knockout (KO) and wild type (WT) mice.
- Applied mechanical stretch of 20% for 10 minutes to cultured cardiac myocytes.
- Measured activity of MAPK family and c-fos gene expression post-stretch.
- Mechanical stretch activated ERKs in both KO and WT myocytes, with KO myocytes showing higher basal and stimulated ERK levels.
- An AT1 antagonist reduced ERK activation in WT myocytes but had no effect on KO myocytes.
- Stretching KO myocytes led to phosphorylation of the epidermal growth factor receptor, indicating an alternative signaling pathway.
Structured PICO
P
Population
Cultured cardiac myocytes of Angiotensin II type 1a receptor (AT1a) knockout (KO) mice and wild type (WT) mice
I
Intervention
Mechanical stretch (20% for 10 min) with or without AT1 antagonist, protein kinase C down-regulation, tyrosine kinase inhibitor (genistein), or selective EGFR inhibitors (tyrphostin, AG1478, B42)
C
Comparator
Unstretched myocytes and wild type (WT) myocytes
O
Outcome
Activity of mitogen-activated protein kinase (MAPK) family (ERKs, p38) and expression of the c-fos genesurrogate
Mechanical stretch can evoke hypertrophic responses in cardiac myocytes lacking the AT1 signaling pathway, possibly through tyrosine kinase and epidermal growth factor receptor activation.
Cite This Study
Kudoh et al. (1998) studied this question.