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Alpha-1-antitrypsin in serum exosomes and pericardial fluid exosomes is associated with severity of rheumatic heart disease

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Abstract

Rheumatic heart disease (RHD) is an autoimmune sequel of pharyngitis and rheumatic fever that leads to permanent heart valve damage, especially the mitral valves. The mitral valves, which are responsible for the binding of auto-antibodies during immune response generation, lead to valve scarring and eventually valves dysfunction. Recently, exosomes (EXOs), the nano-sized vesicles, which range in size from 30 to 150 nm, are reported in various cardiovascular physiological and pathological processes. These vesicles are found in several body fluids such as plasma, serum, and also in cell culture media. Exosomal cargo contains proteins, which are taken up by the recipient cells and modulate the cellular characteristics. The role of exosomal proteins in RHD is still obscure. Hence, the present study has been designed to unveil the exosomal proteins in disease severity during RHD. In this study, the exosomes were isolated from biological fluids (serum and pericardial fluid) of RHD patients as well as from their respective controls. Protein profiling of these isolated exosomes revealed that alpha-1 antitrypsin is up-regulated in the biological fluids of RHD patients. The enhanced levels of exosomal alpha-1 antitrypsin, were further, validated in biological samples and mitral valve tissues of RHD patients, to correlate with the disease severity. These findings suggest an association of increased levels of exosomal alpha-1 antitrypsin with the RHD pathogenesis.

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Funding

The funding was received by Indian Council of Medical Research (ICMR), Delhi, India.

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Author notes

  1. Subendu Sarkar

    Present address: ESIC Medical College and Hospital, NH-3, NIT, Faridabad, India

Authors and Affiliations

  1. Department of Experimental Medicine and Biotechnology, Postgraduate Institute of Medical Education and Research (PGIMER), Sector -12, Chandigarh, 160012, India

    Shruti Sharma, Subendu Sarkar, Chinmayee Choudhury, Lakhwinder Singh & Anuradha Chakraborti

  2. Department of Cardiothoracic & Vascular Surgery, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India

    Harkant Singh

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Contributions

SSa designed the framework, performed the experimental work and drafted the manuscript. CCa## helped in bioinformatics analysis. SSa# analysed the data and contributed in drafting the manuscript. LSa### helped in drafting the manuscript. HSb provided the samples for the study. ACa* conceived the idea, designed the study and finalized the MS. The authors approved the final version of the manuscript.

Corresponding author

Correspondence to Anuradha Chakraborti.

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Compliance with Ethical Standards

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Ethical approval

Approval for the study was granted by Institutional Ethics Committee, Postgraduate Institute of Medical Education and Research, Chandigarh (INT/IEC/2017/1437; Date: 04.12.2017).

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Informed consent was obtained from all individual participants included in the study.

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Sharma, S., Sarkar, S., Choudhury, C. et al. Alpha-1-antitrypsin in serum exosomes and pericardial fluid exosomes is associated with severity of rheumatic heart disease. Mol Cell Biochem 478, 1383–1396 (2023). https://doi.org/10.1007/s11010-022-04595-x

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