How the initial compensatory response transition to permanent modifications of cardiac structure and heart failure after myocardial infraction? (547.7)

MI is the first and most significant clinical manifestation of coronary artery disease (CAD). MI initiates a complex sequence of events in left ventricle (LV) leading to structural remodeling. Clinically LV remodeling is manifested through changes in the size, shape and function of heart. Though initial reorientation of ventricular structure is an adaptive response to functional loss of myocardium however, these compensatory changes can transition to permanent modifications leading to heart failure. Partially the transition from compensatory response to functional de‐compensation is linked with impaired calcium homeostasis. Here, I examine the proposal that calcium homeostasis is regulated through a local signaling cascade in cardiomyocytes. The proposal is based on observations that only a very few second messengers can control the complex and diverse functions of cardiac cells. Therefore, it is essential that signaling in cardiomyocytes be compartmentalized to allow diverse stimuli to produce stimuli‐specific responses. Here, through a systems biology approach I show that in cardiomyocytes the local DAG signaling is regulated through a two compartment signaling system. My results imply that after large MI local homeostasis of DAG is disrupted and the loss of this balance leads to prolonged activation of PKC a key molecular target linked with LV remodeling and dysfunctional filling and ejection characteristics in mammalian heart. This study also proposes an explanation for how the DAG homeostasis is regulated during normal systolic and diastolic functions.