Key result
Angiotensin-converting enzyme-2 metabolizes angiotensin II to angiotensin-(1-7) in the kidney, and its deficiency in mice elevates blood pressure and accelerates glomerulosclerosis.
Angiotensin-converting enzyme-2 plays a critical role in balancing intrarenal angiotensin II and angiotensin-(1-7), presenting a potential therapeutic target for kidney disorders and hypertension.
ACE2 modulation remains investigational for hypertension and kidney disease; leaves open clinical translation from murine models.
PURPOSE OF REVIEW: The intrarenal renin-angiotensin system contributes to the progression of chronic kidney disease. Angiotensin-converting enzyme-2 is a recently identified protein that is highly expressed in the kidney and results in formation of angiotensin-(1-7). This manuscript highlights current information on the localization and function of angiotensin-converting enzyme-2 in the kidney, along with recent studies on the role of the enzyme in hypertension, glomerulosclerosis, and diabetic nephropathy. RECENT FINDINGS: Angiotensin-converting enzyme-2 is expressed in relative abundance in the proximal tubule and metabolizes angiotensin II to angiotensin-(1-7). Angiotensin-converting enzyme-2 also catalyzes conversion of angiotensin I to angiotensin-(1-9), which is cleaved to angiotensin-(1-7) by angiotensin-converting enzyme. In mice, gene deletion of angiotensin-converting enzyme-2 elevates blood pressure responses to angiotensin II, and increases renal angiotensin II levels. Male angiotensin-converting enzyme-2-deficient mice exhibit accelerated glomerulosclerosis. In early diabetic nephropathy, proximal tubular angiotensin-converting enzyme-2 expression and activity are increased, suggesting that the enzyme may counterregulate the effects of local angiotensin II. SUMMARY: Angiotensin-converting enzyme-2 appears to be critical in determining the balance between the intrarenal effects of angiotensin II and angiotensin-(1-7). Angiotensin-converting enzyme-2 could thereby represent a target for novel therapeutic approaches in a variety of kidney disorders.
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Kevin D. Burns (2007) conducted a review in Kidney disorders. Angiotensin-converting enzyme-2 was evaluated. Angiotensin-converting enzyme-2 metabolizes angiotensin II to angiotensin-(1-7) in the kidney, and its deficiency in mice elevates blood pressure and accelerates glomerulosclerosis.
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