N-
acetyl-seryl-aspartyl-lysyl-proline (
Ac-SDKP) is a ubiquitous molecule generated in all mammalian tissues from the N-terminal sequence of
thymosin β4 (Tβ4) by the action of propyl
oligopeptidase.
Ac-SDKP is an alternative substrate for
angiotensin converting enzyme (ACE). There are several indications that
Ac-SDKP may be protective in the cardiovascular system. First, the level of
Ac- SDKP in plasma and tissues is reduced in some cardiovascular pathologies such as
hypertension. Second, an administration of
Ac-SDKP to rodents attenuates
inflammation, cell differentiation, proliferation, and migration resulting in a reduction of
fibrosis in the heart, vessels and kidneys in conditions of their disorders. Third, the treatment with
ACE-inhibitors is associated with a reduced degradation and hence increased levels of
Ac-SDKP, while a simultaneous treatment with
monoclonal antibodies against
Ac- SDKP partly counteracts the benefit of ACE-inhibition. Since
Ac-SDKP fails to reduce blood pressure and
left ventricular hypertrophy (LVH), its potential structural benefit is obviously mediated by direct action on tissue in preventing or reversing excessive
fibrosis. The protection by ACE-inhibition seems to be partly mediated by increased availability of
Ac-SDKP. Thus, it is to suppose that harvesting the knowledge on the role of
Ac-SDKP in cardiovascular physiology and pathology could deepen our insight into the mechanisms of action of the renin-angiotensin system (RAS) as well as agents interfering with this system. The exciting protective potential of
Ac-SDKP suggests that this compound could be a focused
drug target not only in animal experiments but also in the clinical cardio-pharmacologic research in the near future.