Efficacy Assessment and Mechanism Exploration of Haptoglobin Phenotyping and Peptide Supplementation Strategy for Restenosis

Abstract

Restenosis is a common complication after balloon angioplasty, and the major mechanism is associated with abnormal proliferation, migration and cellular inflammation of vascular smooth muscle cells. However, its therapeutic diagnosis and treatment as well as the fundamental molecular mechanisms have not been fully established. Different haptoglobin (Hp) phenotypes have been clinically confirmed to be related to the incidence of restenosis, and various Hp subunits have also been found to have a variety of cellular activities, which have the potential to inhibit restenosis. Previous studies have shown that patients with Hp 1‐1 phenotype have the least incidence of restenosis. Therefore, the main axis of this study is to evaluate the efficacies and safeties of the Hp subunits as protein drugs for preventing restenosis, as well as exploring their possible regulatory mechanisms. We have constructed the expression vectors of different Hp subunits to understand the regulatory activities of these subunits on critical signaling pathways. Rat carotid artery balloon‐injury model was used to evaluate the efficacies, additive effects, and possible toxicities of potential Hp subunit on preventing restenosis. The outcomes of this project will help us to understand the feasibility, efficacy and safety of the Hp subunit as protein drugs for preventing vascular restenosis.