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

Advanced Science

卷:7

Ashraf M. Mohieldin¹  Rajasekharreddy Pala¹  Ashwaq Alanazi¹  Kiumars Shamloo¹  Surya M. Nauli¹  Rinzhin T. Sherpa¹  Madhawi Alanazi¹  James J. Moresco²  John R. Yates III²  Wissam A. AbouAlaiwi³  Amir Ahsan⁴ 

[1] Department of Biomedical and Pharmaceutical Sciences Chapman University Irvine CA 92618 USA;

[2] Department of Molecular Medicine The Scripps Research Institute La Jolla CA 92037 USA;

[3] Department of Pharmacology and Experimental Therapeutics University of Toledo Toledo OH 43614 USA;

[4] Department of Physics, Computer Science and Engineering Chapman University Orange CA 92866 USA;

关键词: aortic stenosis;    arrythmia;    cardiac edema;    extracellular vesicles;    fibrosis;    hypotension;   

DOI  :  10.1002/advs.201903140

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown