Abstract Body: Pulmonary arterial hypertension(PAH) is rare but deadly disease characterized by increased pressure in the pulmonary circulation. A critical aspect of disease progression is the hypertrophic remodeling of the medial layer of pulmonary arteries which is largely comprised of smooth muscle cells (SMC). IN PAH, SMC undergo phenotypic transition from contractile cells to those with high rate of proliferation. While the current treatments for PAH extend life, there is no cure and therapeutics targeting SMC proliferation are an unmet need. To identify novel genes regulating proliferation, we interrogated rat and human PAH datasets and identified Anillin (ANLN) as potential mediator of SMC proliferation. ANLN is an actin binding protein that is upregulated in numerous cancers that coordinates cytokinesis as well as non-mitotic functions regulating gene expression and cell migration among others. We found that ANLN mRNA expression was increased both rat PH and human PAH along with upregulation of many ANLN binding partners. ANLN protein expression was also increased in both human disease and in rodent models of pulmonary hypertension (monocrotaline (rats) or Sugen hypoxia(mice)). In pulmonary arterial smooth muscle cells (PASMCs) cultured from rat pulmonary arteries, we found that PASMC from MCT-treated rats with PH maintain an elevated level of proliferation and ANLN expression compared to PASMC from control rats. To assess whether high ANLN expression impacted increased proliferation, we knocked down ANLN expression using siRNA. Reduced ANLN expression decreased proliferation in HPASMCs and RPASMCs. Interestingly, SMCs migration was unchanged. ANLN protein stability is regulated by the APC/C (anaphase promoting complex/cyclosome). The APC/C consists of the core protein, CDH1 or CDC20, along with additional components. Over expression of CDH1 or its dominant negative mutant led to decreased or increased ANLN protein expression, respectively. Pharmacological inhibition of the APC/C with APCIN in HPASMCs resulted in a significant decrease in ANLN expression. Furthermore, treatment of HPASMCs and RPASMCs with APCIN resulted in a decrease in proliferation. Collectively this data suggests that ANLN is a novel target gene that is important for SMC proliferation in PAH.