ACE and rheumatoid arthritis: Another potential explanation for synovial hypoxia could be the enhanced expression of angiotensin converting enzyme (ACE), a membrane metalloprotease that catalyzes the formation of angiotensin II from its inactive precursor, angiotensin I. Angiotensin II is a potent vasoconstrictor and ACE is overexpressed in stromal cells in RA synovial tissue, generating local vasoconstriction and enhancing hypoxia [37].