Cardiac angiotensin II formation: the angiotensin-I converting enzyme and human chymase.

Angiotensin-I converting enzyme (ACE) inhibitors have provided a remarkable improvement in the treatment of patients with primary hypertension and congestive heart failure. The cardiac renin-angiotensin system is one of the major targets of ACE inhibitor therapy since recent studies show that the human heart contains high affinity angiotensin II (Ang II) receptors and ACE activity. However, it is not clear why ACE inhibitors are more effective than other vasodilators in the treatment of patients with congestive heart failure. This gap in knowledge led us to study the biochemical mechanism of Ang II formation in the human heart. Such studies have only recently been addressed. So far, two Ang II-forming enzymes (ACE and human chymase) have been identified. Unlike in the rat heart, the minor (10%) component of Ang II-forming activity in the left ventricle is due to ACE, whereas the major (80%) component is due to human chymase. This novel cardiac serine proteinase has been purified from the human left ventricle and characterized, and recently, the cDNA and the gene for this enzyme have been cloned. Biochemical characterization revealed that human chymase is the most efficient and specific Ang II-forming enzyme described thus far, but the cellular and regional distribution of two Ang II-forming enzymes seem to be quite different. ACE is localized mainly in endothelial cells and its expression level is higher in atria than ventricles whereas chymase is localized in the interstitial region of the myocardium and its expression is higher in ventricles than atria.(ABSTRACT TRUNCATED AT 250 WORDS)