Just the beginning: novel functions for angiotensin-converting enzymes.
Cardiovascular disease is predicted to be the commonest cause of death worldwide by the year 2020. Diabetes, smoking and hypertension are the main risk factors. The renin-angiotensin system plays a key role in regulating blood pressure and fluid and electrolyte homeostasis in mammals. The discovery of specific drugs that block either the key enzyme of the renin-angiotensin system, angiotensin-converting enzyme (ACE), or the receptor for its main effector angiotensin II, was a major step forward in the treatment of hypertension and heart failure. In recent years, however, the renin-angiotensin system has been shown to be a far more complex system than initially thought. It has become clear that additional peptide mediators are involved. Furthermore, a new ACE, angiotensin-converting enzyme 2 (ACE2), has been discovered which appears to negatively regulate the renin-angiotensin system. In the heart, ACE2 deficiency results in severe impairment of cardiac contractility and upregulation of hypoxia-induced genes. We shall discuss the interplay of the various effector peptides generated by angiotensin-converting enzymes ACE and ACE2, highlighting the role of ACE2 as a negative regulator of the renin-angiotensin system.
Eriksson
Urs
U
IMBA, Institute for Molecular Biotechnology of the Austrian Academy of Sciences, A-1030 Vienna, Austria.
Danilczyk
Ursula
U
Penninger
Josef M
JM
D000595:Amino Acid Sequence; D000818:Animals; D051379:Mice; D007703:Peptidyl-Dipeptidase A / Q000737:chemistry / Q000378:metabolism*
D007703:Peptidyl-Dipeptidase A