Discovery of angiotensin converting enzyme (ACE)-2 provided a strong impetus for the development of novel
therapeutic tools for the treatment of cardiovascular diseases (CVDs). Angiotensin (Ang)-(1-7), the product of ACE2, via
activation of Mas receptor elicits cardiovascular protective effects to a large extent by counter-regulating ACE/Ang-
II/AT1-receptor axis of renin angiotensin system (RAS).
Bone marrow (BM)-derived progenitor cells play an important role in cardiovascular homeostasis. Angiogenic precursor
cells (APCs) have received tremendous attention in the recent years for their therapeutic application for treatment of
CVDs, where cardiovascular tissue regeneration is the desired outcome. Autologous cell therapy is a better treatment
option for patients with cardiovascular complications. However, circulating APCs from these patients are dysfunctional
limiting their therapeutic utility. Thus ex vivo modification to restore their regenerative potential is essential to improve
outcomes of autologous cell therapies in CVD.
Members of both pathological and protective axes of RAS have been identified in one or more types of BM-derived cells.
Modulation of the function of APCs by Ang-II or Ang-(1-7) has now been implicated in the pathology and protection of
cardiovascular systems, respectively. Thus, novel functions of RAS in the cardiovascular regenerative physiology and
pharmacology are being unraveled. Accumulating evidence points to the ACE2/Ang-(1-7)/Mas axis as a promising target
for the treatment of CVDs. The major focus of this review is to highlight the protective role of ACE2/Ang-(1-7)/Mas
pathway in the reparative function of BM-derived cells for cardiovascular repair and regeneration.
Keywords: ACE2, Angiogenic precursor cells, Angiotensin-(1-7), Cardiovascular regeneration, Mas receptor, cardiac hypertrophy, autoregulatory mechanism, ACE2/Ang-(1-7)/Mas receptor, myocardial contractility
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