Beikoghli Kalkhoran, S;
Basalay, M;
He, Z;
Golforoush, P;
Roper, T;
Caplin, B;
Salama, AD;
... Yellon, DM; + view all
(2024)
Investigating the cause of cardiovascular dysfunction in chronic kidney disease: capillary rarefaction and inflammation may contribute to detrimental cardiovascular outcomes.
Basic Research in Cardiology
10.1007/s00395-024-01086-6.
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Abstract
Myocardial ischemia–reperfusion (IR) injury is a major cause of morbidity and mortality in patients with chronic kidney disease (CKD). The most frequently used and representative experimental model is the rat dietary adenine-induced CKD, which leads to CKD-associated CVD. However, the continued intake of adenine is a potential confounding factor. This study investigated cardiovascular dysfunction following brief adenine exposure, CKD development and return to a normal diet. Male Wistar rats received a 0.3% adenine diet for 10 weeks and normal chow for an additional 8 weeks. Kidney function was assessed by urinalysis and histology. Heart function was assessed by echocardiography. Sensitivity to myocardial IR injury was assessed using the isolated perfused rat heart (Langendorff) model. The inflammation profile of rats with CKD was assessed via cytokine ELISA, tissue histology and RNA sequencing. Induction of CKD was confirmed by a significant increase in plasma creatinine and albuminuria. Histology revealed extensive glomerular and tubular damage. Diastolic dysfunction, measured by the reduction of the E/A ratio, was apparent in rats with CKD even following a normal diet. Hearts from rats with CKD had significantly larger infarcts after IR injury. The CKD rats also had statistically higher levels of markers of inflammation including myeloperoxidase, KIM-1 and interleukin-33. RNA sequencing revealed several changes including an increase in inflammatory signaling pathways. In addition, we noted that CKD induced significant cardiac capillary rarefaction. We have established a modified model of adenine-induced CKD, which leads to cardiovascular dysfunction in the absence of adenine. Our observations of capillary rarefaction and inflammation suggest that these may contribute to detrimental cardiovascular outcomes.
| Type: | Article |
|---|---|
| Title: | Investigating the cause of cardiovascular dysfunction in chronic kidney disease: capillary rarefaction and inflammation may contribute to detrimental cardiovascular outcomes |
| Location: | Germany |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1007/s00395-024-01086-6 |
| Publisher version: | https://doi.org/10.1007/s00395-024-01086-6 |
| Language: | English |
| Additional information: | This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
| Keywords: | Chronic kidney disease, Heart, Inflammation, Ischaemia, Reperfusion injury |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Renal Medicine UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Pre-clinical and Fundamental Science |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10200400 |
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