Prolylcarboxypeptidase (PRCP) regulates plasma prekallikrein/high molecular weight
kininogen/bradykinin axis. It also modulates angiotensin II (Ang II), angiotensin III (Ang III), and
alpha-melanocyte stimulating hormone (α-MSH) physiological effects. Study suggests that increased
plasma PRCP level is associated with cardiovascular risk factors, such as atherosclerosis, inflammation,
and diabetes. Since expression pattern of PRCP in Zucker diabetic fatty (ZDF) rat vascular tissue
remain unproved, we aimed to study its expression in the heart and kidney. The purpose of the present study was also to
obtain systemic information of inflammation status with regard to PRCP expression and function in a high-fat diet (HFD)-
fed ZDF rats. The ZDF rats were divided into 2 groups, which were fed a high-fat diet for 16 weeks or 32 weeks.
Differential expression and pathological significance of PRCP expression during the consecutive stages of renal disease
development were identified. After 16 weeks, ZDF rats exhibited early transiently altered PRCP expression in the heart
and kidneys. After 32 weeks, ZDF rats showed continuously altered expression in PRCP and inflammatory markers,
which was linked to severe hyperglycemia and nephropathy. Altered expression of PRCP associated with inflammatory
mediators was illustrated to be functionally relevant. In further support of an important role of PRCP, we found PRCP
protein to be highly elevated in rat plasma and in human plasma and the anti-diabetic agents reversed it. These findings
indicate that impairment of tissues within the cardiovascular system influences PRCP expression and suggest that
pathogenic mechanisms of deregulated PRCP expression warrant further investigation.