Abstract Body: Introduction:
Failure of the right ventricle (RV) is a main component of the morbidity and mortality of pulmonary hypertension (PH). There exists no specific treatment for RV dysfunction and failure and the only cure for many patients (especially in the case of pulmonary arterial hypertension) remains transplantation. This is partially due to the critical lack of understanding of RV biology; therapeutic strategies that are beneficial for LV failure have worse outcomes when applied to those with RV failure. RV dysfunction is characterized by exaggerated fibrosis and divergent contractile and hypertrophic responses to several drugs when compared to LV dysfunction. Thus, the RV may contain distinct cellular physiology compared to the LV that has high significance for the treatment of PH.

Methods:
Tissue digests from the RV and LV of Sprague Dawley rats were collected. We utilized digests to collect RNA for RNA-seq, and prepared cells for flow cytometry and fibroblast isolations. Fibroblasts were cultured for proliferation assays and cell signaling studies.

Results:
We found that the RV and LV have significant differences in expression of immune-related and fibrotic genes. The RV of control rats had an average of four-fold higher density of immune cells, namely macrophages/monocytes, compared to the LV (P<0.05 via paired t-test). Fibroblasts from the RV of control rats, which had a higher proliferation rate and an alteration of metabolic genes than those from the LV (P<0.05 via two-way ANOVA), also had a higher fold-change increase in periostin and CTGF expression upon treatment with TGFβ.

Conclusions:
The results demonstrate that in comparison to the LV, the RV is made up of a unique population of cells and has a unique capacity for fibrotic response that is reflected in its molecular makeup, which may contribute to its distinct response to PH. Future experiments will focus on determining the molecular mechanisms driving these differences. This knowledge is expected to yield new therapeutic approaches for RV dysfunction and failure occurring with PH, which currently have no specific treatment.