The anti-inflammatory peptide Ac-SDKP: Synthesis, role in ACE inhibition, and its therapeutic potential in hypertension and cardiovascular diseases.
Pharmacological research : the official journal of the Italian Pharmacological Society
Cardiovascular diseases (CVDs) represent ∼31% of all global deaths, and hypertension alone accounts for ∼50% of these cases. Inflammation and subsequent fibrosis in heart, kidney and brain are associated with increased morbidity and mortality in CVD patients. N-Acetyl-Seryl-Aspartyl-Proline (Ac-SDKP) is a naturally occurring immunomodulatory and pro-angiogenic peptide mainly released from its precursor thymosin β4 (Tβ4) via enzymatic hydrolysis involving meprin-α and prolyl-oligopeptidase, while Ac-SDKP degradation is primarily carried out by angiotensin converting enzyme (ACE). Keeping its immunomodulatory and angiogenic properties in view, numerous studies have focused on its beneficial effects in cardiovascular diseases. Research in the past 20 years involving heart, kidney and brain injury show that, treatment with Ac-SDKP ameliorates end-organ damage in part, by reducing inflammation, fibrosis and by promoting angiogenesis. Clinical studies involving ACE inhibitor therapy have shown increased plasma and tissue Ac-SDKP concentration, and some of the beneficial effects of ACE inhibitors in hypertension are partly due to increased Ac-SDKP content. Interestingly, these protective effects of Ac-SDKP are independent of blood-pressure regulation. This review discusses the Ac-SDKP biology in health and disease conditions, identifying its possible mechanisms of action, and explore potential use of Ac-SDKP as a novel treatment for CVDs.