SCUBE1 Controls BMPR2-Relevant Pulmonary Endothelial Function: Implications for Diagnostic Marker Development in Pulmonary Arterial Hypertension

Wei Sun; Ying Tang; Yi Yin Tai; Adam Handen; Jingsi Zhao; Gil Speyer; Yassmin Al Aaraj; Annie Watson; Makenna E. Romanelli; John Sembrat; Mauricio Rojas; Marc A. Simon; Yingze Zhang; Janet Lee; Zeyu Xiong; Partha Dutta; Sathish Badu Vasamsetti; Dennis McNamara; Bryan McVerry; Charles F. McTiernan; Frank C. Sciurba; Seungchan Kim; Kerri Akaya Smith; Jeremy A. Mazurek; Yuchi Han; Anjali Vaidya; Seyed Mehdi Nouraie; Neil J. Kelly; Stephen Y. Chan

doi:10.1016/j.jacbts.2020.08.010

SCUBE1 Controls BMPR2-Relevant Pulmonary Endothelial Function: Implications for Diagnostic Marker Development in Pulmonary Arterial Hypertension

Wei Sun, Ying Tang, Yi Yin Tai, Adam Handen, Jingsi Zhao, Gil Speyer, Yassmin Al Aaraj, Annie Watson, Makenna E. Romanelli, John Sembrat, Mauricio Rojas, Marc A. Simon, Yingze Zhang, Janet Lee, Zeyu Xiong, Partha Dutta, Sathish Badu Vasamsetti, Dennis McNamara, Bryan McVerry, Charles F. McTiernanFrank C. Sciurba, Seungchan Kim, Kerri Akaya Smith, Jeremy A. Mazurek, Yuchi Han, Anjali Vaidya, Seyed Mehdi Nouraie, Neil J. Kelly, Stephen Y. Chan

Research output: Contribution to journal › Article › peer-review

11 Scopus citations

Abstract

Utilizing publicly available ribonucleic acid sequencing data, we identified SCUBE1 as a BMPR2-related gene differentially expressed between induced pluripotent stem cell-endothelial cells derived from pulmonary arterial hypertension (PAH) patients carrying pathogenic BMPR2 mutations and control patients without mutations. Endothelial SCUBE1 expression was decreased by known triggers of PAH, and its down-regulation recapitulated known BMPR2-associated endothelial pathophenotypes in vitro. Meanwhile, SCUBE1 concentrations were reduced in plasma obtained from PAH rodent models and patients with PAH, whereas plasma concentrations were tightly correlated with hemodynamic markers of disease severity. Taken together, these data implicate SCUBE1 as a novel contributor to PAH pathogenesis with potential therapeutic, diagnostic, and prognostic applications.

Original language	English
Pages (from-to)	1073-1092
Number of pages	20
Journal	JACC: Basic to Translational Science
Volume	5
Issue number	11
DOIs	https://doi.org/10.1016/j.jacbts.2020.08.010
State	Published - Nov 2020

Keywords

BMPR2
SCUBE1
endothelium
pulmonary hypertension

Access to Document

10.1016/j.jacbts.2020.08.010

Cite this

Sun, W., Tang, Y., Tai, Y. Y., Handen, A., Zhao, J., Speyer, G., Al Aaraj, Y., Watson, A., Romanelli, M. E., Sembrat, J., Rojas, M., Simon, M. A., Zhang, Y., Lee, J., Xiong, Z., Dutta, P., Vasamsetti, S. B., McNamara, D., McVerry, B., ... Chan, S. Y. (2020). SCUBE1 Controls BMPR2-Relevant Pulmonary Endothelial Function: Implications for Diagnostic Marker Development in Pulmonary Arterial Hypertension. JACC: Basic to Translational Science, 5(11), 1073-1092. https://doi.org/10.1016/j.jacbts.2020.08.010

@article{19189034fc4541b4a085285dc4122c0b,

title = "SCUBE1 Controls BMPR2-Relevant Pulmonary Endothelial Function: Implications for Diagnostic Marker Development in Pulmonary Arterial Hypertension",

abstract = "Utilizing publicly available ribonucleic acid sequencing data, we identified SCUBE1 as a BMPR2-related gene differentially expressed between induced pluripotent stem cell-endothelial cells derived from pulmonary arterial hypertension (PAH) patients carrying pathogenic BMPR2 mutations and control patients without mutations. Endothelial SCUBE1 expression was decreased by known triggers of PAH, and its down-regulation recapitulated known BMPR2-associated endothelial pathophenotypes in vitro. Meanwhile, SCUBE1 concentrations were reduced in plasma obtained from PAH rodent models and patients with PAH, whereas plasma concentrations were tightly correlated with hemodynamic markers of disease severity. Taken together, these data implicate SCUBE1 as a novel contributor to PAH pathogenesis with potential therapeutic, diagnostic, and prognostic applications.",

keywords = "BMPR2, SCUBE1, endothelium, pulmonary hypertension",

author = "Wei Sun and Ying Tang and Tai, {Yi Yin} and Adam Handen and Jingsi Zhao and Gil Speyer and {Al Aaraj}, Yassmin and Annie Watson and Romanelli, {Makenna E.} and John Sembrat and Mauricio Rojas and Simon, {Marc A.} and Yingze Zhang and Janet Lee and Zeyu Xiong and Partha Dutta and Vasamsetti, {Sathish Badu} and Dennis McNamara and Bryan McVerry and McTiernan, {Charles F.} and Sciurba, {Frank C.} and Seungchan Kim and Smith, {Kerri Akaya} and Mazurek, {Jeremy A.} and Yuchi Han and Anjali Vaidya and Nouraie, {Seyed Mehdi} and Kelly, {Neil J.} and Chan, {Stephen Y.}",

note = "Publisher Copyright: {\textcopyright} 2020",

year = "2020",

month = nov,

doi = "10.1016/j.jacbts.2020.08.010",

language = "English",

volume = "5",

pages = "1073--1092",

journal = "JACC: Basic to Translational Science",

issn = "2452-302X",

number = "11",

}

Sun, W, Tang, Y, Tai, YY, Handen, A, Zhao, J, Speyer, G, Al Aaraj, Y, Watson, A, Romanelli, ME, Sembrat, J, Rojas, M, Simon, MA, Zhang, Y, Lee, J, Xiong, Z, Dutta, P, Vasamsetti, SB, McNamara, D, McVerry, B, McTiernan, CF, Sciurba, FC, Kim, S, Smith, KA, Mazurek, JA, Han, Y, Vaidya, A, Nouraie, SM, Kelly, NJ & Chan, SY 2020, 'SCUBE1 Controls BMPR2-Relevant Pulmonary Endothelial Function: Implications for Diagnostic Marker Development in Pulmonary Arterial Hypertension', JACC: Basic to Translational Science, vol. 5, no. 11, pp. 1073-1092. https://doi.org/10.1016/j.jacbts.2020.08.010

TY - JOUR

T1 - SCUBE1 Controls BMPR2-Relevant Pulmonary Endothelial Function

T2 - Implications for Diagnostic Marker Development in Pulmonary Arterial Hypertension

AU - Sun, Wei

AU - Tang, Ying

AU - Tai, Yi Yin

AU - Handen, Adam

AU - Zhao, Jingsi

AU - Speyer, Gil

AU - Al Aaraj, Yassmin

AU - Watson, Annie

AU - Romanelli, Makenna E.

AU - Sembrat, John

AU - Rojas, Mauricio

AU - Simon, Marc A.

AU - Zhang, Yingze

AU - Lee, Janet

AU - Xiong, Zeyu

AU - Dutta, Partha

AU - Vasamsetti, Sathish Badu

AU - McNamara, Dennis

AU - McVerry, Bryan

AU - McTiernan, Charles F.

AU - Sciurba, Frank C.

AU - Kim, Seungchan

AU - Smith, Kerri Akaya

AU - Mazurek, Jeremy A.

AU - Han, Yuchi

AU - Vaidya, Anjali

AU - Nouraie, Seyed Mehdi

AU - Kelly, Neil J.

AU - Chan, Stephen Y.

PY - 2020/11

Y1 - 2020/11

N2 - Utilizing publicly available ribonucleic acid sequencing data, we identified SCUBE1 as a BMPR2-related gene differentially expressed between induced pluripotent stem cell-endothelial cells derived from pulmonary arterial hypertension (PAH) patients carrying pathogenic BMPR2 mutations and control patients without mutations. Endothelial SCUBE1 expression was decreased by known triggers of PAH, and its down-regulation recapitulated known BMPR2-associated endothelial pathophenotypes in vitro. Meanwhile, SCUBE1 concentrations were reduced in plasma obtained from PAH rodent models and patients with PAH, whereas plasma concentrations were tightly correlated with hemodynamic markers of disease severity. Taken together, these data implicate SCUBE1 as a novel contributor to PAH pathogenesis with potential therapeutic, diagnostic, and prognostic applications.

AB - Utilizing publicly available ribonucleic acid sequencing data, we identified SCUBE1 as a BMPR2-related gene differentially expressed between induced pluripotent stem cell-endothelial cells derived from pulmonary arterial hypertension (PAH) patients carrying pathogenic BMPR2 mutations and control patients without mutations. Endothelial SCUBE1 expression was decreased by known triggers of PAH, and its down-regulation recapitulated known BMPR2-associated endothelial pathophenotypes in vitro. Meanwhile, SCUBE1 concentrations were reduced in plasma obtained from PAH rodent models and patients with PAH, whereas plasma concentrations were tightly correlated with hemodynamic markers of disease severity. Taken together, these data implicate SCUBE1 as a novel contributor to PAH pathogenesis with potential therapeutic, diagnostic, and prognostic applications.

KW - BMPR2

KW - SCUBE1

KW - endothelium

KW - pulmonary hypertension

UR - http://www.scopus.com/inward/record.url?scp=85097436541&partnerID=8YFLogxK

U2 - 10.1016/j.jacbts.2020.08.010

DO - 10.1016/j.jacbts.2020.08.010

M3 - Article

AN - SCOPUS:85097436541

SN - 2452-302X

VL - 5

SP - 1073

EP - 1092

JO - JACC: Basic to Translational Science

JF - JACC: Basic to Translational Science

IS - 11

ER -

SCUBE1 Controls BMPR2-Relevant Pulmonary Endothelial Function: Implications for Diagnostic Marker Development in Pulmonary Arterial Hypertension

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this