Understanding the machinery of cardiac cells that allows them to sense and respond to mechanical stress brings us closer to targeted therapy of heart failure.
Increased mechanical stress is a hallmark of heart failure progression, resulting from the underlying cause of disease and can also manifest during disease development. Both the cardiac myocytes and cardiac fibroblasts respond to this increased stress, which can escalate the development of changes in the heart that promote cardiac disease. Here, we identify two receptors from different mechanoreceptor families crucial to the early cardiac remodeling response to increased afterload. We show that syndecan-4 and integrin α11β1 are involved in the stress response to increased afterload, promoting cardiac hypertrophy and collagen production. Preventing expression of these receptors ablated early cardiac hypertrophic remodeling and decreased collagen production. Dual-receptor targeting of mechanoreceptors to reduce adverse cardiac remodeling secondary to increased afterload may therefore be a viable future therapy.