University of Kentucky
Impact of Cardiomyocyte-Restricted Deletion of RAD on Voluntary Exercise and Cardiac Remodeling
Grade Level at Time of Presentation
Senior
Major
Biology
Institution 24-25
University of Kentucky
KY House District #
2
KY Senate District #
36
Faculty Advisor/ Mentor
Jonathan Satin, PhD
Department
Department of Physiology
Abstract
Background: RAD regulates calcium current through the Cav1.2 channel. Cardiomyocyte- restricted deletion of RAD (cRADKO) improves calcium channel activity and systolic function in healthy mice, but the impact of cRADKO on voluntary exercise and its impact on cardiac communication with extracardiac tissue is unexplored. The impact of cRADKO on voluntary exercise in a cardiomyopathy (DCM) model is also unexplored. An athlete’s heart has overlapping features of DCM including LV chamber dilation with a decreased ejection fraction.
Hypothesis: cRADKO will pre-adapt the heart to exercise. cRADKO in DCM will move the heart towards healthy.
Methods: cRADKO mice were injected with tamoxifen at 6 weeks and placed on running wheels at 9 weeks. To measure exercise, we used the Progressive Weighted-wheel-Running (PoWeR) model of mouse exercise training; it provides voluntary exercise without stressing the mice. We collected echo data at the start and end of the 8-week training time. We are measuring cardiomyocyte cell size, cardiac fibrosis, and capillary density. To evaluate extra- cardiac effects we harvested soleus, gastrocnemius, and plantaris muscles to measure muscle fiber type, fiber size, and myonuclear density. We are also measuring oxygen consumption in cardiac mitochondria.
Results: We found no significant difference in voluntary exercise activity between the wildtype and the cRADKO mice. cRADKO mice showed elevated EF at baseline and cRADKO prevented changes in EF or chamber dimension. cRADKO LV thickness increased compared to WT. Found no changes in heart structure or in vivo function with exercise. DCM mouse running data is in progress of being measured.
Future Directions and Expected Results: WT and cRadKO indistinguishable total exercise eliminate differential exercise as a variable, thus permitting evaluation of gene knockout effect. cRadKO in sedentary healthy background does not alter any known signaling pathways. To assess cRadKO effect on physiological hypertrophic signaling I will be measuring candidate signaling intermediaries. Athletes heart masquerades as DCM and is mainly seen in males. Our WT mice on PoWeR recapitulated human athletes heart, and cRadKO pre-adapted the heart to exercise.
Impact of Cardiomyocyte-Restricted Deletion of RAD on Voluntary Exercise and Cardiac Remodeling
Background: RAD regulates calcium current through the Cav1.2 channel. Cardiomyocyte- restricted deletion of RAD (cRADKO) improves calcium channel activity and systolic function in healthy mice, but the impact of cRADKO on voluntary exercise and its impact on cardiac communication with extracardiac tissue is unexplored. The impact of cRADKO on voluntary exercise in a cardiomyopathy (DCM) model is also unexplored. An athlete’s heart has overlapping features of DCM including LV chamber dilation with a decreased ejection fraction.
Hypothesis: cRADKO will pre-adapt the heart to exercise. cRADKO in DCM will move the heart towards healthy.
Methods: cRADKO mice were injected with tamoxifen at 6 weeks and placed on running wheels at 9 weeks. To measure exercise, we used the Progressive Weighted-wheel-Running (PoWeR) model of mouse exercise training; it provides voluntary exercise without stressing the mice. We collected echo data at the start and end of the 8-week training time. We are measuring cardiomyocyte cell size, cardiac fibrosis, and capillary density. To evaluate extra- cardiac effects we harvested soleus, gastrocnemius, and plantaris muscles to measure muscle fiber type, fiber size, and myonuclear density. We are also measuring oxygen consumption in cardiac mitochondria.
Results: We found no significant difference in voluntary exercise activity between the wildtype and the cRADKO mice. cRADKO mice showed elevated EF at baseline and cRADKO prevented changes in EF or chamber dimension. cRADKO LV thickness increased compared to WT. Found no changes in heart structure or in vivo function with exercise. DCM mouse running data is in progress of being measured.
Future Directions and Expected Results: WT and cRadKO indistinguishable total exercise eliminate differential exercise as a variable, thus permitting evaluation of gene knockout effect. cRadKO in sedentary healthy background does not alter any known signaling pathways. To assess cRadKO effect on physiological hypertrophic signaling I will be measuring candidate signaling intermediaries. Athletes heart masquerades as DCM and is mainly seen in males. Our WT mice on PoWeR recapitulated human athletes heart, and cRadKO pre-adapted the heart to exercise.