Kallistatin: A Novel Biomarker for Hypertension, Organ Injury and Cancer

Kallistatin has pleiotropic effects in vasodilation and inhibition of inflammation, angiogenesis, oxidative stress, fibrosis, and cancer progression. Kallistatin administration by gene or protein delivery is observed to offer protection against a large number of pathological conditions in animal models, such as hypertension, cardiovascular and organ damage, arthritis, sepsis, influenza virus infection, tumor growth and metastasis. However, injection of a neutralizing Kallistatin antibody into hypertensive rats aggravates cardiovascular and renal injury in association with increased inflammation, oxidative stress and tissue remodeling. Thus, animal studies show that kallistatin treatment exerts beneficial effects against hypertension, organ damage and cancer development. Moreover, serum kallistatin levels are markedly reduced in several animal models of hypertension and cardiac, cerebral and renal injury. Importantly, kallistatin levels in circulation, body fluids or tissues are significantly lower in patients with liver disease, septic syndrome, diabetic retinopathy, severe pneumonia, inflammatory bowel disease, and cancer of the colon and prostate. Furthermore, reduced plasma kallistatin levels are associated with adiposity and metabolic risk in apparently healthy African American youths. The focus of this review is to highlight circulating kallistatin as a potential new biomarker for human diseases.