Renalase deficiency aggravates ischemic myocardial damage.

• Type: Article in International Scientific Journal
• Date: 2011

Authors

Wu Y (Author) Other; Xu J (Author) Other; Velazquez P (Author) Other; Wang G (Author) Other; Li G (Author) Other; Liu D (Author) Other; Benedita Sampaio-Maia (Author) FMDUP; Quelhas Santos, J (Author) Other; Russell K (Author) Other; Russell R (Author) Other; Flavell RA (Author) Other; Giodarno F (Author) Other; Desir GV (Author) Other; Manuel Pestana (Author) FMUP

Journal

Title: Kidney International

Vol. 79 No. 8

Pages: 853-860

ISSN: 0085-2538

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 124 Citations

ISI Web of Science

Scopus - 133 Citations

Pubmed / Medline

Scientific classification

FOS: Medical and Health sciences > Basic medicine

CORDIS: Health sciences > Medical sciences > Medicine

Other information

Authenticus ID: P-002-STA

Abstract (EN): Chronic kidney disease (CKD) leads to an 18-fold increase in cardiovascular complications not fully explained by traditional risk factors. Levels of renalase, a recently discovered oxidase that metabolizes catecholamines, are decreased in CKD. Here we show that renalase deficiency in a mouse knockout model causes increased plasma catecholamine levels and hypertension. Plasma blood urea nitrogen, creatinine, and aldosterone were unaffected. However, knockout mice had normal systolic function and mild ventricular hypertrophy but tolerated cardiac ischemia poorly and developed myocardial necrosis threefold more severe than that found in wild-type mice. Treatment with recombinant renalase completely rescued the cardiac phenotype. To gain insight into the mechanisms mediating this cardioprotective effect, we tested if gene deletion affected nitrate and glutathione metabolism, but found no differences between hearts of knockout and wild-type mice. The ratio of oxidized (NAD) to reduced (NADH) nicotinamide adenine dinucleotide in cardiac tissue, however, was significantly decreased in the hearts of renalase knockout mice, as was plasma NADH oxidase activity. In vitro studies confirmed that renalase metabolizes NADH and catecholamines. Thus, renalase plays an important role in cardiovascular pathology and its replacement may reduce cardiac complications in renalase-deficient states such as CKD.

Language: English

Type (Professor's evaluation): Scientific