The Epidermal growth factor receptor (EGFR), a receptor tyrosine kinase, can be activated by binding of e.g. epidermal growth factor or heparin-bound growth factor. Under baseline conditions cardiomyocyte (CM) EGFR prevents excessive hypertrophic growth through its impact on ROS balance, while in vascular smooth muscle cells (VSMC) EGFR contributes to the appropriate vascular wall architecture and vessel reactivity, thereby supporting a physiological vascular tone. But EGFR can also be transactivated by various vasoactive substances, like e.g. aldosterone, a mediate at leastr part of their imapct. Mice with a global deletion of the EGFR die during embryogenesis, thereby prohibiting the analysis of the effects of the affore mentioned substances mediated by EGFR.

To analyze the in vivo role of this transactivation in the cardiovascular system during aldosterone/NaCl challenge, we generated a mouse model with a deletion of the EGFR in VSMC and a strong reduction in CM. Animals received aldosterone by implanted pellets and 1% NaCl for drinking (aldo/NaCl) or vehicle and water (control) for four weeks.

There was no significant difference in systolic blood pressure during this time interval. There was no change in heart weight/ tibia length upon aldo/NaCl application. We analyzed thereafter the expression of marker genes for fibrosis, inflammation and heart hypertrophy. Revealing a significant difference in the expression of collagen 1a1 in aortas upon aldo/NaCl stimulation.

The presented data show, that the EGFR, beside its function in cardiovascular homeostasis can be transactivated by aldosterone, thereby increasing aldosteron induced vascular fibrosis.