Proteomic Identification Reveals the Role of Ciliary Extracellular-Like Vesicle in Cardiovascular Function

Ashraf M. Mohieldin, Rajasekharreddy Pala, Rinzhin T. Sherpa, Madhawi Alanazi, Ashwaq Alanazi, Kiumars Shamloo, Amir Ahsan, Wissam A. AbouAlaiwi, James J. Moresco, John R. Yates, Surya M. Nauli

Research output: Contribution to journalArticle

Abstract

Primary cilia are shown to have membrane swelling, also known as ciliary bulbs. However, the role of these structures and their physiological relevance remains unknown. Here, it is reported that a ciliary bulb has extracellular vesicle (EV)-like characteristics. The ciliary extracellular-like vesicle (cELV) has a unique dynamic movement and can be released by mechanical fluid force. To better identify the cELV, differential multidimensional proteomic analyses are performed on the cELV. A database of 172 cELV proteins is generated, and all that examined are confirmed to be in the cELV. Repressing the expression of these proteins in vitro and in vivo inhibits cELV formation. In addition to the randomized heart looping, hydrocephalus, and cystic kidney in fish, compensated heart contractility is observed in both fish and mouse models. Specifically, low circulation of cELV results in hypotension with compensated heart function, left ventricular hypertrophy, cardiac fibrosis, and arrhythmogenic characteristics, which result in a high mortality rate in mice. Furthermore, the overall ejection fraction, stroke volume, and cardiac output are significantly decreased in mice lacking cELV. It is thus proposed that the cELV as a nanocompartment within a primary cilium plays an important role in cardiovascular functions.

Original languageEnglish (US)
Article number1903140
JournalAdvanced Science
Volume7
Issue number16
DOIs
StatePublished - Aug 1 2020
Externally publishedYes

Keywords

  • aortic stenosis
  • arrythmia
  • cardiac edema
  • extracellular vesicles
  • fibrosis
  • hypotension
  • primary cilia

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Chemical Engineering(all)
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Materials Science(all)
  • Engineering(all)
  • Physics and Astronomy(all)

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  • Cite this

    Mohieldin, A. M., Pala, R., Sherpa, R. T., Alanazi, M., Alanazi, A., Shamloo, K., Ahsan, A., AbouAlaiwi, W. A., Moresco, J. J., Yates, J. R., & Nauli, S. M. (2020). Proteomic Identification Reveals the Role of Ciliary Extracellular-Like Vesicle in Cardiovascular Function. Advanced Science, 7(16), [1903140]. https://doi.org/10.1002/advs.201903140