Heart failure (HF) is associated with impaired L-arginine transport. In the present study, we tested the hypothesis that augmented L-arginine transport prevents the loss of kidney function in HF. Renal function was assessed in wild-type mice (WT), transgenic mice with HF (DCM) and double transgenic mice (HFCAT-1) with HF and endothelial specific overexpression of the predominant L-arginine transporter, cationic amino acid transporter-1 (CAT-1) (n=8/group). Cardiac function was assessed via echocardiography and left ventricular catheterization. Renal function was assessed via quantification of albuminuria and creatinine clearance. Plasma nitrate and nitrite levels together with renal fibrosis and inflammatory markers were also quantified at study end. Albumin/creatinine ratio was 2 fold greater in DCM mice than in WT mice (P=0.002), and tubulointerstitial and glomerular fibrosis were ̴ 8 and 3 fold greater, respectively, in DCM mice than in WT mice (P ≤ 0.02). Critically, urinary albumin/creatinine ratio and tubulointerstitial and glomerular fibrosis were less in HFCAT-1 mice than in DCM mice (P < 0.05). Renal CAT-1 expression and plasma nitrate and nitrite levels were less in DCM mice compared to WT (P ≤ 0.03) but was greater in HFCAT-1 mice than in DCM mice (P ≤ 0.009). Renal expression of IL-10 was less in DCM mice compared to WT (P < 0.001) but was greater in HFCAT-1 mice compared to DCM mice (P=0.02). Our data provide direct evidence that augmented L-arginine transport prevents renal fibrosis, inflammation and loss of renal function in HF.
Endothelial specific overexpression of cationic amino acid transporter-1 prevents loss of renal function in cardiorenal syndrome type 2
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Beverly Giam, Haru Nomura, Sanjaya Kuruppu, Po-Yin Chu, Sumia Essid, Helen Kiriazis, Xiao-Jun Du, David Kaye, Niwanthi W Rajapakse; Endothelial specific overexpression of cationic amino acid transporter-1 prevents loss of renal function in cardiorenal syndrome type 2. Clin Sci (Lond) CS20200087. doi: https://doi.org/10.1042/CS20200087
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