Structural and Functional Remodeling of the Cardiac Muscle in the Hypertensive Profilin1 Transgenic Mouse Model

Abstract

Pressure overload to the heart, via hypertension, results in cardiac hypertrophy which induces heart failure. We have developed a novel transgenic mouse model by over‐expressing the cDNA of human profilin 1 in the blood vessels of transgenic mice to study cardiovascular dysfunction. Our previous results showed significant increased medial thickness of the microvessels of profilin1 and elevated blood pressure in profilin1 mice starting at age 6 months. Our current study investigates the effects of hypertension on the cardiac muscle structure and function of older profilin 1 mice. Western blotting showed no expression of profilin1 in young profilin 1 mice, but significant activation of profilin1 in older profilin1 mice. The hypertrophic signaling cascade was activated in the cardiac muscle of old profilin 1 mice as demonstrated by increased, ERK1/2, JNK and ROCK II kinase (312.3%, 271.4% and 350% respectively, P<0.05). Our Echocardiography demonstrated decreased LV ejection fraction and fractional shortening (35% and 25%, respectively. P<0.05) and increased LV mass in old profilin 1 mice. In conclusion, the cardiac hypertrophy in profilin 1 transgenic mice is due to activation of profilin 1 in cardiac muscle as a secondary effect of pressure overload. This study will enable us to understand the role of profilin‐associated signaling mechanisms in triggering cardiac hypertrophy in hypertensive humans.