Cardiac Remodeling

A large number of physiological and pathological conditions, like hypertension, are able to generate a cardiac hypertrophic response. The heart modifies its shape as well as its volume in response to a need for altered force production, but, since the heart is a terminally differentiated organ, its adaptations to increased workload are accomplished mainly by increasing muscle mass through hypertrophic remodeling.

Cardiac hypertrophy has, at the beginning, beneficial effects in terms of muscular economy, normalizing wall stress. However, several epidemiological studies have demonstrated that chronic hypertrophy is associated with a significant increase in the risk of heart failure, dilated cardiomyopathy, ischemic heart disease, and sudden death, leading to increased cardiovascular mortality.

Muscle growth and adaptation is a complex, integrative process. In the cell, several regulatory steps can be activated in response to growth signals. A great number of intracellular signaling pathways involved in the hypertrophic response have been characterized in the last decade. All of these molecules do not operate in isolation, but participate in a more orchestrated response that generates interdependent and cross-talking networks. This explains the fact that the mechanisms involved in cardiac hypertrophy are still not completely clear.

Thus, the hypertrophy response can be maladaptive or adaptive, depending on the specific signaling pathways involved. This hypothesis could have significant implications for drug development to control the hypertrophic response and direct it to more favorable outcomes.

In our lab, we are focused on identification of pathways that are involved in cardiac hypertrophy and their role in maladaptive or adaptive remodeling.