title: Tissue angiotensin II system in the human heart.
abstract: Several intervention studies with angiotensin I converting enzyme (ACE) inhibitors have demonstrated a remarkable improvement in the treatment of patients with primary hypertension and congestive heart failure. Since ACE inhibitor therapy in patients with congestive heart failure not only improves systemic haemodynamics but also provides a better prognosis, the cardiac renin-angiotensin system is apparently one of the major targets of ACE inhibitor therapy. Recent studies provided evidence that the human heart contains high affinity Ang II (Ang II) receptors with both subtype population and ACE. In addition to ACE, a novel cardiac Ang II forming enzyme (human chymase) has been identified in human hearts. 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 the two Ang II-forming enzymes seems to be different. ACE is mainly localized in endothelial cells and fibroblasts and the expression level is higher in atria than ventricles, whereas chymase is synthesized and stored in secretory granules of mast cells, endothelial cells, and mesenchymal cells, and after its secretion localized in the interstitial region of the myocardium and its expression is higher in ventricles than atria. These results imply distinct roles of these two Ang II-forming enzymes in cardiac Ang II formation and in the physiological function of the human heart. Since localization of cardiac renin and angiotensinogen were also identified in human heart, it is important to understand the detailed mechanisms of the tissue Ang II formation and its contribution to the pathophysiological changes in cardiovascular diseases.
authors.affiliation: Max-Delbrück-Centre for Molecular Medicine (MDC), Berlin, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Urata
authors.forename: S
authors.initials: S
authors.lastname: Hoffmann
authors.forename: D
authors.initials: D
authors.lastname: Ganten
mesh_terms: D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D016275:Atrial Function; D053818:Chymases; D006333:Heart Failure / Q000503:physiopathology*; D006352:Heart Ventricles / Q000503:physiopathology; D006439:Hemodynamics / Q000502:physiology*; D006801:Humans; D006973:Hypertension / Q000503:physiopathology*; D007703:Peptidyl-Dipeptidase A / Q000502:physiology; D011945:Receptors, Angiotensin / Q000502:physiology; D012084:Renin-Angiotensin System / Q000502:physiology*; D012697:Serine Endopeptidases / Q000502:physiology
chemical_list: D011945:Receptors, Angiotensin; D000804:Angiotensin II; D007703:Peptidyl-Dipeptidase A; D012697:Serine Endopeptidases; D053818:Chymases