Investigation of serum levels of Isthmin-1 and Apela in patients with IPAH

ABSTRACT INVESTIGATION OF SERUM LEVELS OF ISTHMIN-1 AND APELA IN PATIENTS WITH IPAH Idiopathic Pulmonary Arterial Hypertension (IPAH) is a rare and progressive disease with high morbidity and mortality rates, and one of the most important factors determining prognosis is early diagnosis. In this regard, the identification of new biomarkers may facilitate the diagnostic process. Investigating whether serum ISM-1 and APELA levels play a role as potential biomarkers in the diagnosis of IPAH is important for the development of new diagnostic tools that can contribute to early diagnosis. Isthmin-1 (ISM1) and Apela (ELABELA), which have recently been identified in the literature and whose relationships with the cardiovascular system have attracted attention, are considered molecules worth investigating due to their possible effects in vascular diseases such as IPAH. ISM-1 (Isthmin-1) is a newly identified protein thought to be associated with vascular structure, angiogenesis, and inflammation. Apela (ELABELA) is a peptide hormone that plays a role in cardiovascular development; It is effective in processes such as vascular dilation and cell proliferation. This study aims to determine the changes in serum ISM-1 and Apela levels in IPAH patients and to evaluate the possible roles of these molecules in the disease pathophysiology. The study included all patients diagnosed with pulmonary arterial hypertension (PAH) at the Cardiology Clinic of Fırat University Hospital during the first six months of 2025. The study group consisted of 106 patients diagnosed with idiopathic pulmonary arterial hypertension (IPAH), 40 patients with PAH due to congenital heart disease from the Group 1 pulmonary arterial hypertension subgroup, and 30 patients diagnosed with chronic thromboembolic pulmonary hypertension (CTEPH). The control group consisted of 90 healthy volunteers with no personal or family history of pulmonary hypertension and matched to the patient groups in terms of age and gender. In the study, Apela levels were measured as 125.45 ng/L on average in the patient group and 839.15 ng/L in the control group; the difference between the two groups was found to be statistically significant (p < 0.001). ISM-1 levels were found to be 4.47 ng/mL on average in the patient group and 28.39 ng/mL in the control group; this difference was found to be statistically significant (p < 0.001).In the study, both Isthmin-1 and Apela levels were found to be significantly lower in IPAH patients compared to the control group. These biomarkers may play a role in the pathophysiology of IPAH and could be considered potential markers in the diagnosis and monitoring of the disease. However, the obtained data need to be supported by further studies conducted in larger sample groups and across different patient stages. Key Words: Idiopathic Pulmonary Hypertension, Isthmin-1, Apela, Serum biomarkers, Pulmonary vascular diseases