*3.1. Proteasome Inhibitors and Cardiovascular Disorders*

It is well known that the vasculature is an important determinant of BP. UPS ubiquitously regulates tissue function and can regulate BP through its e ffect on blood vessels. Proteasome inhibitors have been clinically used as therapeutic agents for multiple myeloma. Carfilzomib, the first irreversible proteasome inhibitor, was found to bind selectively to its target, the chymotrypsin-like activity of the 20S proteasome [68]. It exhibited a higher e fficacy in the treatment of patients with relapsed and/or refractory multiple myeloma when applied in combination with dexamethasone with or without lenalidomide [69,70]. Since its approval during the year 2010, there have been increasing reports of carfilzomib-associated cardiovascular adverse events, including hypertension. A systematic review and meta-analysis showed that hypertension (12.2%) was most common among carfilzomib-associated cardiovascular adverse events [71], supporting the involvement of UPS in BP control.
