Dataset Information

Whole-Mount Kidney Clearing and Visualization Reveal Renal Sympathetic Hyperinnervation in Heart Failure Mice.

ABSTRACT: Developing a three-dimensional (3D) visualization of the kidney at the whole-mount scale is challenging. In the present study, we optimized mouse whole-mount kidney clearing, which improved the transparency ratio to over 90% based on organ-specific perfusion (OSP)-clear, unobstructed brain imaging cocktails and computational analysis (CUBIC). The optimized OSP-CUBIC-compatible 3D immunostaining and imaging simultaneously visualized the high-resolution 3D structure of the whole-mount renal microvascular, glomerulus, and accompanying wrapped traveling sympathetic nerves in mice. A mouse model of pressure overload-induced heart failure (HF) was then established by minimally invasive transverse aortic constriction (MTAC). Further 3D quantification revealed renal sympathetic hyperinnervation (6.80 ± 1.04% vs. 3.73 ± 0.60%, P < 0.05) in mice with HF. In conclusion, this newly developed whole-organ tissue clearing and imaging system provides comprehensive information at the whole-mount scale and has great potential for kidney research. Our data suggest that renal sympathetic hyperinnervation is involved in HF associated with renal dysfunction.

SUBMITTER: Wu C

PROVIDER: S-EPMC8297621 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Whole-Mount Kidney Clearing and Visualization Reveal Renal Sympathetic Hyperinnervation in Heart Failure Mice.

Wu Chao C Yan Fang F Li Min M Tu Yimin Y Guo Ziyu Z Chen Yufei Y Wu Yaxin Y Li Qing Q Yu Changan C Fu Yi Y Wu Meihui M Kong Wei W Gao Yanxiang Y Li Xiaowei X Zheng Jingang J

Frontiers in physiology 20210708

Developing a three-dimensional (3D) visualization of the kidney at the whole-mount scale is challenging. In the present study, we optimized mouse whole-mount kidney clearing, which improved the transparency ratio to over 90% based on organ-specific perfusion (OSP)-clear, unobstructed brain imaging cocktails and computational analysis (CUBIC). The optimized OSP-CUBIC-compatible 3D immunostaining and imaging simultaneously visualized the high-resolution 3D structure of the whole-mount renal microv ...[more]

PMID: 34305650

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Project description:BackgroundCardiac sympathetic hyperinnervation after myocardial infarction (MI) is associated with arrhythmogenesis and sudden cardiac death. The characteristics of cardiac sympathetic hyperinnervation remain underexposed.ObjectiveTo provide a systematic review on cardiac sympathetic hyperinnervation after MI, taking into account: (1) definition, experimental model and quantification method and (2) location, amount and timing, in order to obtain an overview of current knowledge and to expose gaps in literature.MethodsReferences on cardiac sympathetic hyperinnervation were screened for inclusion. The included studies received a full-text review and quality appraisal. Relevant data on hyperinnervation were collected and qualitatively analysed.ResultsOur literature search identified 60 eligible studies performed between 2000 and 2022. Cardiac hyperinnervation is generally defined as an increased sympathetic nerve density or increased number of nerves compared to another control group (100%). Studies were performed in a multitude of experimental models, but most commonly in male rats with permanent left anterior descending (LAD) artery ligation (male: 63%, rat: 68%, permanent ligation: 93%, LAD: 97%). Hyperinnervation seems to occur mainly in the borderzone. Quantification after MI was performed in regions of interest in µm2/mm2 (41%) or in percentage of nerve fibres (46%) and the reported amount showed a great variation ranging from 439 to 126,718 µm2/mm2. Hyperinnervation seems to start from three days onwards to >3 months without an evident peak, although studies on structural evaluation over time and in the chronic phase were scarce.ConclusionsCardiac sympathetic hyperinnervation after MI occurs mainly in the borderzone from three days onwards and remains present at later timepoints, for at least 3 months. It is most commonly studied in male rats with permanent LAD ligation. The amount of hyperinnervation differs greatly between studies, possibly due to differential quantification methods. Further studies are required that evaluate cardiac sympathetic hyperinnervation over time and in the chronic phase, in transmural sections, in the female sex, and in MI with reperfusion.

Project description:The aim of the present study was to determine if renal sympathetic denervation (RSD) may alleviate isoproterenol-induced left ventricle remodeling, and to identify the underlying mechanism. A total of 70 rats were randomly divided into control (n=15), sham operation (n=15), heart failure (HF) with sham operation (HF + sham; n=20) and HF with treatment (HF + RSD; n=20) groups. The HF model was established by subcutaneous injection of isoproterenol; six weeks later, 1eft ventricular internal diameter at end‑systole (LVIDs), left ventricular systolic posterior wall thickness (LVPWs), 1eft ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were measured. Plasma norepinephrine (NE), angiotensin II (Ang II) and aldosterone (ALD) levels were measured by ELISA. Myocardial collagen volume fraction (CVF) was determined by Masson's staining. Reverse transcription‑quantitative polymerase chain reaction was used to determine the mRNA expression levels of ventricular transforming growth factor‑β (TGF‑β), connective tissue growth factor (CTGF) and microRNAs (miRs), including miR‑29b, miR‑30c and miR‑133a. The results demonstrated that LVIDs and LVPWs in the HF + RSD group were significantly decreased compared with the HF + sham group. By contrast, LVFS and LVEF in the HF + RSD group were significantly increased compared with the HF + sham group. RSD significantly reduced the levels of plasma NE, Ang II and ALD. CVF in the HF + RSD group was reduced by 38.1% compared with the HF + sham group. Expression levels of TGF‑β and CTGF were decreased, whereas those of miR‑29b, miR‑30c and miR‑133a were increased, in the HF + RSD group compared with the HF + sham group. These results indicated that RSD alleviates isoproterenol‑induced left ventricle remodeling potentially via downregulation of TGF‑β/CTGF and upregulation of miR‑29b, miR‑30c and miR‑133a. RSD may therefore be an effective non‑drug therapy for the treatment of heart failure.

Dataset Information

Whole-Mount Kidney Clearing and Visualization Reveal Renal Sympathetic Hyperinnervation in Heart Failure Mice.

Publications

Whole-Mount Kidney Clearing and Visualization Reveal Renal Sympathetic Hyperinnervation in Heart Failure Mice.

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