Angiotensin-converting enzyme 2 regulates heart function

Cardiovascular diseases are predicted to be the most common cause of death worldwide by 2020. The major regulator of blood pressure homeostasis is the renin-angiotensis system. Angiotensinogen is digested by renin to produce angiotensin I (AGT I). AGT I is an inactive 10 amino-acid peptide that is further degraded to produce angiotensin II by the agiotensin-converting enzyme (ACE). Angiotensis II is the master regulator of blood pressure increase acting on the heart, kidneys and blood vessels. Angiotensin II causes direct constriction of the resistance vessels and stimulation of the adrenal cortex to increase blood volume and sodium absorption. In 2000, Tipnis et al., discovered ACE 2 a second carboxypeptidase that digests angiotensin. ACE is a di-peptidase, cleaving off 2 peptides from the c-terminal end of angiotensin. ACE 2 only cleaves 1 amino acid to produce angiotensin 1-9 (AGT 1-9) which has no identified function at this time. AGT 1-9 is not converted to angiotensin II but further degraded by ACE to AGT 1-7, a vasodilator. It would appear that ACE 2 inhibits the formation of angiotensin and reduces blood pressure increases. Crackower et al determined that ace2 -/- mice suffered significant heart defects at 6 months. Further deletion of ACE resulted in restored cardiac functions.

Contributor: Kosi Gramatikoff, PhD

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