TY - JOUR
T1 - Proteomic Identification Reveals the Role of Ciliary Extracellular-Like Vesicle in Cardiovascular Function
AU - Mohieldin, Ashraf M.
AU - Pala, Rajasekharreddy
AU - Sherpa, Rinzhin T.
AU - Alanazi, Madhawi
AU - Alanazi, Ashwaq
AU - Shamloo, Kiumars
AU - Ahsan, Amir
AU - AbouAlaiwi, Wissam A.
AU - Moresco, James J.
AU - Yates, John R.
AU - Nauli, Surya M.
N1 - Funding Information:
The authors thank Armando Diaz for his expertise in generating the videos and Maki Takahashi for preparation of the reagents and technical assistance. This work was supported by the Congressionally Directed Medical Research Program PR130153, NIH HL131577, AHA 19IPLOI34730020, and Chapman University. J.J.M. and J.R.Y. were supported by the National Institute of General Medical Sciences (8P41 GM103533). All animal procedures were performed according to Chapman University Animal Care and Use Committee Guidelines.
Publisher Copyright:
© 2020 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
PY - 2020/8/1
Y1 - 2020/8/1
N2 - 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.
AB - 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.
KW - aortic stenosis
KW - arrythmia
KW - cardiac edema
KW - extracellular vesicles
KW - fibrosis
KW - hypotension
KW - primary cilia
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U2 - 10.1002/advs.201903140
DO - 10.1002/advs.201903140
M3 - Article
C2 - 32832346
AN - SCOPUS:85089613414
VL - 7
JO - Advanced Science
JF - Advanced Science
SN - 2198-3844
IS - 16
M1 - 1903140
ER -