Cardiovascular Risk in Patients With Takayasu Arteritis Directly Correlates With Diastolic Dysfunction and Inflammatory Cell Infiltration in the Vessel Wall: A Clinical, ex vivo and in vitro Analysis

• Published in: Frontiers in medicine Vol. 9; p. 863150
• Main Authors: Cicco, Sebastiano, Desantis, Vanessa, Vacca, Antonio, Cazzato, Gerardo, Solimando, Antonio G, Cirulli, Anna, Noviello, Silvia, Susca, Cecilia, Prete, Marcella, Brosolo, Gabriele, Catena, Cristiana, Lamanuzzi, Aurelia, Saltarella, Ilaria, Frassanito, Maria Antonia, Cimmino, Antonella, Ingravallo, Giuseppe, Resta, Leonardo, Ria, Roberto, Montagnani, Monica
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 16.05.2022
• Subjects: echocardiography; immune cell infiltration; Medicine; Regulatory T Lymphocytes (Tregs); T helper-like cells; Takayasu arteritis (TAK); vascular stiffness; T helper-like cells; Takayasu arteritis (TAK); immune cell infiltration; vascular stiffness; Regulatory T Lymphocytes (Tregs); echocardiography
• ISSN: 2296-858X; 2296-858X
• DOI: 10.3389/fmed.2022.863150

Takayasu Arteritis (TAK) increases vascular stiffness and arterial resistance. Atherosclerosis leads to similar changes. We investigated possible differences in cardiovascular remodeling between these diseases and whether the differences are correlated with immune cell expression. Patients with active TAK arteritis were compared with age- and sex-matched atherosclerotic patients (Controls). In a subpopulation of TAK patients, Treg/Th17 cells were measured before (T0) and after 18 months (T18) of infliximab treatment. Echocardiogram, supraaortic Doppler ultrasound, and lymphocytogram were performed in all patients. Histological and immunohistochemical changes of the vessel wall were evaluated as well. TAK patients have increased aortic valve dysfunction and diastolic dysfunction. The degree of dysfunction appears associated with uric acid levels. A significant increase in aortic stiffness was also observed and associated with levels of peripheral T lymphocytes. CD3 CD4 cell infiltrates were detected in the vessel wall samples of TAK patients, whose mean percentage of Tregs was lower than Controls at T0, but increased significantly at T18. Opposite behavior was observed for Th17 cells. Finally, TAK patients were found to have an increased risk of atherosclerotic cardiovascular disease (ASCVD). Our data suggest that different pathogenic mechanisms underlie vessel damage, including atherosclerosis, in TAK patients compared with Controls. The increased risk of ASCVD in TAK patients correlates directly with the degree of inflammatory cell infiltration in the vessel wall. Infliximab restores the normal frequency of Tregs/Th17 in TAK patients and allows a possible reduction of steroids and immunosuppressants.