Dr Qinghua Cao1, Dr Owen Tang2, Professor Gemma Figtree2, Professor Xin-Ming Chen1, Professor Carol Pollock1
1Renal Medicine, Kolling Institute of Medical Research, Sydney Medical School, Faculty of Medicine and Health, University of Sydney, Royal North Shore Hospital, St leonards, Australia, 2Cardiothoracic and Vascular Health, Kolling Institute of Medical Research, Sydney Medical School, Faculty of Medicine and Health, University of Sydney, Royal North Shore Hospital, St Leonards, Australia
Biography:
Despite being an EMCR, Dr Cao has led or co-led multiple kidney disease projects and published 21 peer-reviewed papers. One of these was published in the high-impact journal JCI Insight and was recognised by the editors as being of “highly significant interest” and featured in the print digest JCI This Month in March 2022. The publication also received “Best Paper Produced by an EMCR at the Kolling Institute”. Dr. Cao received the Inaugural Kolling Institute Emerging Leader Award in 2021. Her current research focus on developing novel therapies to block kidney and cardiac fibrosis in cardiorenal syndrome.
Aim:
To establish a novel, non-surgical and reproducible model of CRS.
Background:
Cardiorenal syndrome (CRS) comprises a spectrum of disorders where heart or kidney dysfunction results in failure of the other. It is highly prevalent in the elderly, leading to frequent hospitalisation and high mortality. Fibrosis, including cardiac and kidney fibrosis, is a common factor in both cardiovascular disease (CVD) and chronic kidney disease (CKD) with CXCR4 upregulated in fibrotic tissues. Current treatments have limitations, highlighting the urgent need for innovative therapies. Animal models are invaluable for exploring potential therapeutic strategies before translating into human studies. Existing CRS animal models often exhibit high variability, surgical mortality, off-target toxicity, and poor human relevance. To address this, we propose a dietary intervention model to induce concomitant kidney and cardiac fibrosis.
Methods:
Aged female C57BL/6 mice (18-22 months) were randomly divided into 2 groups (n=5 per group): (1) Control group receiving a standard diet and water for 16 weeks; (2) CRS group fed a high fat diet (HFD) (Rodent diet with 60 kcal% Fat) and N[w]-nitro-l-arginine methyl ester (L-NAME)(0.5 g/L in the drinking water) for 16 weeks. Blood pressure and heart function were monitored twice weekly. At endpoint, mice were sacrificed for heart and kidney collection. CXCR4 was measured by immunohistochemistry (IHC) and fibrosis was evaluated using HE and Picrosirius Red (PSR) staining.
Results:
L-NAME+HFD induced significant kidney and cardiac fibrosis compared to controls. PSR staining revealed a 1.1-fold increase in the heart and a 2.1-fold increase in the kidney.
Conclusions:
The L-NAME + HFD model may serve as a valuable tool for studying anti-fibrotic therapies in CRS.