P227 MACROPHAGE TO MYOFIBROBLAST TRANSITION IN THE DEVELOPMENT OF DIASTOLIC DYSFUNCTION

Diastolic dysfunction (DD) and heart failure (HF) ravage a significant portion of the world's population. These end-stage diseases are most often precluded by hypertension (HTN). Cardiac fibrosis is one of the major factors in the degradation of cardiac function. There are multiple cellular players involved in fibrosis—including, macrophages. Indeed, in the past decade these cells have been shown to differentiate into professional fibrotic cells, myofibroblasts, a process termed macrophage to myofibroblast transition (MMT), in models of kidney injury. Despite this, the role of MMT in fibrotic remodeling in HTN and DD remains unknown. As such, we seek to investigate this phenomenon in the HTN heart and determine the role it plays in the pathological progression of HTN to DD. We utilized cardiac ultrasound and direct left ventricular (LV) pressure catheterization to gauge diastolic function. These gold-standard methods allowed us to assess cardiac function during HTN and investigate the heart at the transition to DD. Furthermore, flow cytometry was utilized to identify MMT cells (α-SMA+, CD68+) in the heart. These methods gave insight into the role that MMT plays in the degradation of heart function during HTN that inevitably leads to DD and HF. Cardiac ultrasound revealed that E/A and deceleration time (DcT) were greatly decreased in DOCA mice 10 days after the start of HTN. Further, LV pressure catheterization revealed decreased cardiac function, as shown by decreased -dp/dt. Finally, HTN and normal hearts were harvested and leukocytes isolated. Indeed α-SMA and CD68 staining showed a significant increase in MMT cells in the HTN heart. This study has shown a rapid onset of DD inside of DOCA + salt HTN mice. In addition, there was a significant increase of MMT cells in these same hearts, elucidating a novel mechanism of cardiac fibrosis. Future studies will aim to parse out the gravity of MMT in HTN to find new pharmaceutical targets against this debilitating disease.