Myeloid cell-specific deletion of epidermal growth factor receptor aggravates acute cardiac injury.

Myeloid cells, including macrophages, play important roles as first responders to cardiac injury and stress. Epidermal growth factor receptor (EGFR) has been identified as a mediator of macrophage responsiveness to select diseases, though its impact on cardiac function or remodeling following acute ischemic injury is unknown. We aimed to define the role of myeloid cell-specific EGFR in the regulation of cardiac function and remodeling following acute myocardial infarction (MI)-induced injury.

Pepducin ICL1-9-Mediated β2-Adrenergic Receptor-Dependent Cardiomyocyte Contractility Occurs in a G Protein/ROCK/PKD-Sensitive Manner.

Purpose: β-Adrenergic receptors (βAR) are essential targets for the treatment of heart failure (HF); however, chronic use of βAR agonists as positive inotropes to increase contractility in a G protein-dependent manner is associated with increased mortality. Alternatively, we previously reported that allosteric modulation of β2AR with the pepducin intracellular loop (ICL)1-9 increased cardiomyocyte contractility in a β-arrestin (βarr)-dependent manner, and subsequently showed that ICL1-9 activates the Ras homolog family member A (RhoA). Here, we aimed to elucidate both the proximal and downstream signaling mediators involved in the promotion of cardiomyocyte contractility in response to ICL1-9.

Epidermal growth factor receptor-dependent maintenance of cardiac contractility.

Aims: Epidermal growth factor receptor (EGFR) is essential to the development of multiple tissues and organs and is a target of cancer therapeutics. Due to the embryonic lethality of global EGFR deletion and conflicting reports of cardiac-overexpressed EGFR mutants, its specific impact on the adult heart, normally or in response to chronic stress, has not been established. Using complimentary genetic strategies to modulate cardiomyocyte-specific EGFR expression, we aim to define its role in the regulation of cardiac function and remodelling.

G protein-coupled receptor kinase 5 (GRK5) contributes to impaired cardiac function and immune cell recruitment in post-ischemic heart failure.

Aims: Myocardial infarction (MI) is the most common cause of heart failure (HF) worldwide. G protein-coupled receptor kinase 5 (GRK5) is upregulated in failing human myocardium and promotes maladaptive cardiac hypertrophy in animal models. However, the role of GRK5 in ischemic heart disease is still unknown.

Leukocyte-Dependent Regulation of Cardiac Fibrosis.

Cardiac fibrosis begins as an intrinsic response to injury or ageing that functions to preserve the tissue from further damage. Fibrosis results from activated cardiac myofibroblasts, which secrete extracellular matrix (ECM) proteins in an effort to replace damaged tissue; however, excessive ECM deposition leads to pathological fibrotic remodeling. At this extent, fibrosis gravely disturbs myocardial compliance, and ultimately leads to adverse outcomes like heart failure with heightened mortality.