A recent study published in the journal “Nutrition, Metabolism and Cardiovascular Diseases” suggests that elevated levels of circulating microRNA miR-423-5p are associated with the occurrence and severity of carotid atherosclerosis in patients with chronic kidney disease (CKD). The study presents significant insights into the molecular interactions between CKD and cardiovascular diseases, potentially leading to better diagnostic and therapeutic approaches.

The Burden of Carotid Atherosclerosis in CKD

Carotid atherosclerosis, characterized by the build-up of plaques in the carotid arteries, is a major risk factor for stroke in individuals with CKD. The molecular mechanisms underlying the association of carotid atherosclerosis with CKD have, until now, been poorly understood. With stroke being a leading cause of death and disability worldwide, uncovering these mechanisms is crucial for the millions affected by both conditions.

Groundbreaking Research

The study, conducted under the lead of Dr. Yuzhi Huang and colleagues from the First Affiliated Hospital of Xi’an Jiao Tong University and Xi’an People’s Hospital (Xi’an Fourth Hospital), is a cross-sectional investigation involving 375 participants, including both CKD patients undergoing dialysis and those not dependent on it.

The researchers measured the levels of miR-423-5p, a microRNA molecule, through quantitative PCR analysis in plasma and exosomes (tiny vesicles released by cells). The study found that non-dialysis CKD patients had higher circulating exosomal and plasma miR-423-5p levels compared to their dialysis-dependent counterparts.

Findings and Clinical Implications

A negative correlation was established between circulating miR-423-5p levels and estimated Glomerular Filtration Rate (eGFR), with a higher miR-423-5p level associated with the presence and severity of carotid plaques. The study results indicate that miR-423-5p could serve as a biomarker in CKD patients for the risk of developing carotid atherosclerosis.

To complement the human study, the team developed a murine model of CKD using a 5/6 nephrectomy protocol and performed RNA sequencing on aortic tissues from the mice. The findings from the mouse model were in line with the human data, with an increase in circulating exosomal miR-423-5p levels observed in CKD mice.

Mechanistic Insights from RNA Sequencing

In the RNA sequencing studies of the aortic tissues from the CKD mice, researchers identified that the putative target genes of miR-423-5p were involved in oxidative stress pathways—an aspect known to contribute to atherosclerosis. These results suggest that miR-423-5p could be influencing gene expression related to oxidative stress in the aorta of CKD patients, thereby promoting atherogenesis.

Potential for New Therapeutic Targets

The identification of miR-423-5p as a key player in the development of carotid atherosclerosis in CKD patients opens the door for innovative therapeutic strategies targeting this microRNA. Therapies that could modulate the levels or activity of miR-423-5p might prove beneficial in reducing the cardiovascular risks associated with CKD.

No Conflicts of Interest

The study authors have declared no conflicts of interest in their research, underscoring the integrity of the findings reported.

Published by Elsevier B.V.

The publication of the study is by Elsevier B.V., highlighting the importance and international relevance of the research findings.

DOI and References

The study can be accessed with the DOI: 10.1016/j.numecd.2023.12.018, providing a direct link to the research for further reading.

In terms of references, the study adds to a body of work that has been exploring the connections between CKD, cardiovascular health, and molecular biology. Five significant references that contributed to the backdrop against which this study was conducted include:

1. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. Go AS, et al. N Engl J Med. 2004;351(13):1296-1305. DOI: 10.1056/NEJMoa041031.
2. MicroRNAs in kidney function and disease. Lorenzen JM, Thum T. Transl Res. 2016;168:66-75. DOI: 10.1016/j.trsl.2015.06.007.
3. Oxidative stress in cardiovascular disease: molecular basis of its deleterious effects, its detection, and therapeutic considerations. Madamanchi NR, Runge MS. Curr Hypertens Rep. 2007;9(6):488-496. DOI: 10.1007/s11906-007-0088-8.
4. Carotid intima-media thickness and cardiovascular events. Lorenz MW, et al. N Engl J Med. 2012;366(4):321-329. DOI: 10.1056/NEJMoa1012592.
5. The role of microRNAs in chronic kidney disease and cardiovascular disease. Chau BN, Brenner DA. J Pathol. 2011;223(1):4-13. DOI: 10.1002/path.2806.

Keywords

1. Chronic Kidney Disease Cardiovascular Risk
2. miR-423-5p Carotid Atherosclerosis
3. CKD Stroke Biomarkers
4. miRNA Therapeutics in Atherosclerosis
5. Oxidative Stress CKD Impact

Conclusion

This landmark study contributes significantly to our understanding of the molecular interactions between CKD and cardiovascular diseases, providing a promising biomarker for assessing the risk of carotid atherosclerosis. The findings promise advancements in precision medicine and the development of targeted therapeutics, thereby improving the cardiovascular health of CKD patients.