Abstract 15285: Notch3 is Required for the Cardiac Adaptation to Hypertension

Background: The Notch3 receptor has a role in the integrity of resistance arteries by controlling the maturation of vascular smooth muscle cells (VSMC). Hypertension in Notch3 null mice (N3-/-) rapidly induced a heart failure. The mechanistic pathways being not defined, we hypothesize that alterations of the coronary tree secondary to Notch3 invalidation might trigger the development of heart failure in response to hypertension. Methods: N3-/- and WT C57/Bl6J mice were used. At 11 week of age, WT and N3-/- mice were implanted with Alzet mini-pumps filled with Angiotensin 2 (Ang2, 1μg/kg/min) or NaCl for 28 days (n=15-23/ group). Results: Normotensive N3-/- mice showed ventricular hypertrophy (+20%, p Conclusion: Altogether, these data demonstrate that Notch3 activation in the VSMC of coronary artery plays a key role in the adaptation of the heart to Ang2- induced hypertension, and in turn in the development of heart failure.