More than just a small left ventricle: the right ventricular fibroblast and ECM in health and disease

Fibroblasts intricately organize and regulate the extracellular matrix (ECM) in cardiac health and disease. Excess deposition of ECM proteins causes fibrosis, resulting in disrupted signaling conduction and contributing to the development of arrhythmias and impaired cardiac function. Fibrosis is causally involved in cardiac failure in the left ventricle (LV). Fibrosis likely occurs in right ventricle (RV) failure, yet mechanisms remain unclear. Indeed, RV fibrosis is poorly understood with mechanisms often extrapolated from the LV to the RV. However, emerging data suggest that the LV and RV are distinct cardiac chambers and differ in regulation of the ECM and response to fibrotic stimuli. In the present review, we will discuss differences in ECM regulation in the healthy RV and LV. We will discuss the importance of fibrosis in the development of RV disease in pressure overload, inflammation, and aging. During this discussion, we will highlight mechanisms of fibrosis with respect to the synthesis of ECM proteins while acknowledging the importance of considering collagen breakdown. We will also discuss current knowledge of antifibrotic therapies in the RV and the need for additional research to help delineate the shared and distinct mechanisms of RV and LV fibrosis.

Automated summary

Fibroblasts play a crucial role in the organization and regulation of the extracellular matrix (ECM) in the heart. Excess deposition of ECM proteins leads to fibrosis, resulting in disrupted signaling conduction and contributing to cardiac dysfunction. While the mechanisms of left ventricle (LV) fibrosis are well-studied, the mechanisms of right ventricle (RV) fibrosis remain unclear. This review discusses the differences in ECM regulation and the importance of fibrosis in RV disease, highlighting the need for further research on the shared and distinct mechanisms of RV and LV fibrosis.