Endothelial dysfunction in patients with systemic AL amyloidosis

Background. Research related to the state of blood vessels in systemic AL amyloidosis (AL-A) is mostly done on experimental models. The pathogenetic and clinical significance of vascular dysfunction in patients with AL-A is poorly understood. Aim. To study the levels of endothelial dysfunction markers in patients with AL-A at the onset of the disease and after anti-tumor therapy. Materials and methods. The study group included 30 patients with AL-A. The comparison group consisted of 10 patients with multiple myeloma (MM), and the control group included 10 healthy individuals. Patients with AL-A were divided into 2 groups: the first group included 20 patients who underwent the full planned induction therapy, and the second group included 10 patients whose treatment was stopped due to a significant increase in N-terminal pro-brain natriuretic peptide (NTproBNP) levels. The levels of asymmetric dimethylarginine (ADMA), big endothelin (bET), and E-selectin were measured by enzyme-linked immunosorbent assay in serum before and after completion (or premature cessation) of anti-tumor therapy. Results. Patients with AL-A had significantly higher levels of E-selectin and ADMA in serum compared to patients with MM and healthy individuals. An increase in at least one marker of endothelial dysfunction (E-selectin and ADMA) was observed in 27 (90%) patients with AL-A at disease onset. There were no differences in bET levels. In all patients in the first group, reaching hematologic remission was associated with a decrease in E-selectin and ADMA levels compared to baseline values (p0.001). In 5 (55%) out of 9 patients with hematologic and organ response, ADMA levels decreased to normal values. In all patients of the second group, the increase in NTproBNP was accompanied by a significant increase in ADMA (p=0.005) and E-selectin (p=0.007) levels compared to baseline values. Adverse cardiovascular events were observed in 80% of patients with elevated NTproBNP levels. The increase in cardiac markers during anti-tumor therapy was more common in advanced stages of heart involvement. Stage IIIA AL-A was present in 23% of patients in the first group and 70% in the second group (p=0.003). After discontinuation of therapy, the levels of cardiac markers decreased to baseline values, which ruled out disease progression. Conclusion. A pronounced endothelial dysfunction was observed in 90% of patients with AL-A. Reduction in endothelial dysfunction markers was observed upon achieving hematologic and organ response. Anti-tumor therapy in patients with amyloid cardiomyopathy can cause additional endothelial damage, resulting in increased NTproBNP levels and cardiovascular complications.