Genetically increased angiotensin I-converting enzyme level and renal complications in the diabetic mouse

AUTOR(ES)

Huang, Wei

FONTE

The National Academy of Sciences

RESUMO

Diabetic nephropathy is a major risk factor for end-stage renal disease and cardiovascular diseases and has a marked genetic component. A common variant (D allele) of the angiotensin Iconverting enzyme (ACE) gene, determining higher enzyme levels, has been associated with diabetic nephropathy. To address causality underlying this association, we induced diabetes in mice having one, two, or three copies of the gene, normal blood pressure, and an enzyme level range (65–162% of wild type) comparable to that seen in humans. Twelve weeks later, the three-copy diabetic mice had increased blood pressures and overt proteinuria. Proteinuria was correlated to plasma ACE level in the three-copy diabetic mice. Thus, a modest genetic increase in ACE levels is sufficient to cause nephropathy in diabetic mice.

Documentos Relacionados

• Naturally occurring active N-domain of human angiotensin I-converting enzyme.
• Two putative active centers in human angiotensin I-converting enzyme revealed by molecular cloning.
• A continuous fluorescent assay for the determination of plasma and tissue angiotensin I-converting enzyme activity
• Alteration of granuloma angiotensin I-converting enzyme activity by regulatory T lymphocytes in murine schistosomiasis.
• GC–MS based metabolite profiling and angiotensin I-converting enzyme inhibitory property of black tea extracts