ANGIOTENSIN-I CONVERTING-ENZYME AND CHYMASE IN CARDIOVASCULAR TISSUES

Recent studies have provided evidence that the human cardiovascular ti ssues contain components of the renin-angiotensin system: angiotensino gen, renin, angiotensin I converting enzyme (ACE), chymase and angiote nsin II (Ang II) receptors. In addition to ACE, a cardiac Ang II formi ng serine proteinase, human heart chymase, has been identified in the human left ventricle. Unlike rat heart, only a minor (approximate to 1 1%) component of Ang II forming activity in the human left ventricle w as due to ACE, since the majority (approximate to 8O%) of activity was due to chymase. Human heart chymase has been purified to homogeneity and characterized. Recently, the cDNA and gene for this enzyme have be en cloned. Biochemical characterization revealed that heart chymase is the most efficient and specific Ang II forming enzyme described thus far. The different cellular and regional distribution of ACE and heart chymase in the heart as well as in blood vessels implies distinct pat hophysiological roles for these two Ang II forming enzymes. Several re ports indicate that ACE-independent Ang II formation appears to rake p lace in hypoxic or ischemic heart or blood vessel in vivo and to be in volved in vascular remodeling after balloon injury. Therefore, it is v ery important to clarify the detailed mechanisms of the tissue Ang II formation in humans and its contribution to the pathophysiological cha nges in cardiovascular disease. In this review, we review the pathophy siological roles of the two main Ang II forming enzymes, ACE and chyma se, in cardiovascular homeostasis.