Human Left Ventricle circRNA-miRNA-mRNA Network Analyses Reveal a Novel Proangiogenic Role for circNPHP1 Under Ischemic Conditions

Maryam Anwar; Moumita Sarkar; Kerrie Ford; Gianni D. Angelini; Prakash P. Punjabi; Yingshu Guan; Abas Laftah; Aránzazu Chamorro-Jorganes; Jiahui Ji; Prashant K. Srivastava; Enrico Petretto; Costanza Emanueli

doi:10.1016/j.jacbts.2025.101468

Human Left Ventricle circRNA-miRNA-mRNA Network Analyses Reveal a Novel Proangiogenic Role for circNPHP1 Under Ischemic Conditions

Maryam Anwar^*, Moumita Sarkar, Kerrie Ford, Gianni D. Angelini, Prakash P. Punjabi, Yingshu Guan, Abas Laftah, Aránzazu Chamorro-Jorganes, Jiahui Ji, Prashant K. Srivastava, Enrico Petretto, Costanza Emanueli^*

^*Corresponding author for this work

Research output: Contribution to journal › Article (Academic Journal) › peer-review

Abstract

Therapies promoting microvascular flow and endothelial repair require effective identification of new targets in ischemic heart disease (IHD). The aim of this study was to unravel and functionally investigate circular RNA (circRNA)-microRNA (miRNA)-messenger RNA (mRNA) networks in endothelial cells in the context of IHD and type 2 diabetes mellitus (T2DM). We performed RNA sequencing on left ventricle biopsies from patients with IHD, IHD and T2DM, and non-IHD. Next, we created circRNA-miRNA-mRNA networks and mechanistically investigated the top circRNA-miRNA sponging interactions in endothelial cells. We found that circNPHP1 promotes angiogenesis via sponging of miR-221-3p and regulates its downstream target genes, VEGFA and BCL2, in IHD and T2DM.

Original language	English
Article number	101468
Pages (from-to)	101468
Journal	JACC: Basic to Translational Science
Volume	11
Issue number	2
Early online date	22 Jan 2026
DOIs	https://doi.org/10.1016/j.jacbts.2025.101468
Publication status	Published - 1 Feb 2026

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© 2026, The Authors.

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Anwar, M., Sarkar, M., Ford, K., Angelini, G. D., Punjabi, P. P., Guan, Y., Laftah, A., Chamorro-Jorganes, A., Ji, J., Srivastava, P. K., Petretto, E., & Emanueli, C. (2026). Human Left Ventricle circRNA-miRNA-mRNA Network Analyses Reveal a Novel Proangiogenic Role for circNPHP1 Under Ischemic Conditions. JACC: Basic to Translational Science, 11(2), 101468. Article 101468. https://doi.org/10.1016/j.jacbts.2025.101468

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title = "Human Left Ventricle circRNA-miRNA-mRNA Network Analyses Reveal a Novel Proangiogenic Role for circNPHP1 Under Ischemic Conditions",

abstract = "Therapies promoting microvascular flow and endothelial repair require effective identification of new targets in ischemic heart disease (IHD). The aim of this study was to unravel and functionally investigate circular RNA (circRNA)-microRNA (miRNA)-messenger RNA (mRNA) networks in endothelial cells in the context of IHD and type 2 diabetes mellitus (T2DM). We performed RNA sequencing on left ventricle biopsies from patients with IHD, IHD and T2DM, and non-IHD. Next, we created circRNA-miRNA-mRNA networks and mechanistically investigated the top circRNA-miRNA sponging interactions in endothelial cells. We found that circNPHP1 promotes angiogenesis via sponging of miR-221-3p and regulates its downstream target genes, VEGFA and BCL2, in IHD and T2DM.",

author = "Maryam Anwar and Moumita Sarkar and Kerrie Ford and Angelini, \{Gianni D.\} and Punjabi, \{Prakash P.\} and Yingshu Guan and Abas Laftah and Ar{\'a}nzazu Chamorro-Jorganes and Jiahui Ji and Srivastava, \{Prashant K.\} and Enrico Petretto and Costanza Emanueli",

note = "Publisher Copyright: {\textcopyright} 2026, The Authors. ",

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doi = "10.1016/j.jacbts.2025.101468",

language = "English",

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Anwar, M, Sarkar, M, Ford, K, Angelini, GD, Punjabi, PP, Guan, Y, Laftah, A, Chamorro-Jorganes, A, Ji, J, Srivastava, PK, Petretto, E & Emanueli, C 2026, 'Human Left Ventricle circRNA-miRNA-mRNA Network Analyses Reveal a Novel Proangiogenic Role for circNPHP1 Under Ischemic Conditions', JACC: Basic to Translational Science, vol. 11, no. 2, 101468, pp. 101468. https://doi.org/10.1016/j.jacbts.2025.101468

TY - JOUR

T1 - Human Left Ventricle circRNA-miRNA-mRNA Network Analyses Reveal a Novel Proangiogenic Role for circNPHP1 Under Ischemic Conditions

AU - Anwar, Maryam

AU - Sarkar, Moumita

AU - Ford, Kerrie

AU - Angelini, Gianni D.

AU - Punjabi, Prakash P.

AU - Guan, Yingshu

AU - Laftah, Abas

AU - Chamorro-Jorganes, Aránzazu

AU - Ji, Jiahui

AU - Srivastava, Prashant K.

AU - Petretto, Enrico

AU - Emanueli, Costanza

PY - 2026/2/1

Y1 - 2026/2/1

N2 - Therapies promoting microvascular flow and endothelial repair require effective identification of new targets in ischemic heart disease (IHD). The aim of this study was to unravel and functionally investigate circular RNA (circRNA)-microRNA (miRNA)-messenger RNA (mRNA) networks in endothelial cells in the context of IHD and type 2 diabetes mellitus (T2DM). We performed RNA sequencing on left ventricle biopsies from patients with IHD, IHD and T2DM, and non-IHD. Next, we created circRNA-miRNA-mRNA networks and mechanistically investigated the top circRNA-miRNA sponging interactions in endothelial cells. We found that circNPHP1 promotes angiogenesis via sponging of miR-221-3p and regulates its downstream target genes, VEGFA and BCL2, in IHD and T2DM.

AB - Therapies promoting microvascular flow and endothelial repair require effective identification of new targets in ischemic heart disease (IHD). The aim of this study was to unravel and functionally investigate circular RNA (circRNA)-microRNA (miRNA)-messenger RNA (mRNA) networks in endothelial cells in the context of IHD and type 2 diabetes mellitus (T2DM). We performed RNA sequencing on left ventricle biopsies from patients with IHD, IHD and T2DM, and non-IHD. Next, we created circRNA-miRNA-mRNA networks and mechanistically investigated the top circRNA-miRNA sponging interactions in endothelial cells. We found that circNPHP1 promotes angiogenesis via sponging of miR-221-3p and regulates its downstream target genes, VEGFA and BCL2, in IHD and T2DM.

U2 - 10.1016/j.jacbts.2025.101468

DO - 10.1016/j.jacbts.2025.101468

M3 - Article (Academic Journal)

SN - 2452-302X

VL - 11

SP - 101468

JO - JACC: Basic to Translational Science

JF - JACC: Basic to Translational Science

IS - 2

M1 - 101468

ER -

Human Left Ventricle circRNA-miRNA-mRNA Network Analyses Reveal a Novel Proangiogenic Role for circNPHP1 Under Ischemic Conditions

Abstract

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