Evidence map›Paper›PMID 42458593›Full record

ArticleBiology direct2026

PDZK1 is downregulated in ovariectomized mice with angiotensin II-induced hypertension and interacts with β2-AR to regulate endothelial ERK1/2/c-Fos signaling.

Haoran Zhang, Yan Meng, Wenjing Zheng, Wenjie Bu, Wenxiu Liu, Xiaohui Zhang, Zhiyu Shi, Chunnan Liu, Meng Zhao, Huiying Wang and 3 more

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Article in Biology direct, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

13 authors.

Haoran Zhang *Department of Cardiology, First Affiliated Hospital of Harbin Medical University, No. 199 Dazhi Street, Harbin, Heilongjiang, 150001, China.
Yan Meng *Department of Cardiology, First Affiliated Hospital of Harbin Medical University, No. 199 Dazhi Street, Harbin, Heilongjiang, 150001, China.
Wenjing ZhengDepartment of Cardiology, First Affiliated Hospital of Harbin Medical University, No. 199 Dazhi Street, Harbin, Heilongjiang, 150001, China.
Wenjie BuDepartment of Pharmacology, College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang, 150001, China.
Wenxiu LiuDepartment of Cardiology, First Affiliated Hospital of Harbin Medical University, No. 199 Dazhi Street, Harbin, Heilongjiang, 150001, China.
Xiaohui ZhangDepartment of Cardiology, First Affiliated Hospital of Harbin Medical University, No. 199 Dazhi Street, Harbin, Heilongjiang, 150001, China.
Zhiyu ShiDepartment of Cardiology, First Affiliated Hospital of Harbin Medical University, No. 199 Dazhi Street, Harbin, Heilongjiang, 150001, China.
Chunnan LiuDepartment of Cardiology, First Affiliated Hospital of Harbin Medical University, No. 199 Dazhi Street, Harbin, Heilongjiang, 150001, China.
Meng ZhaoDepartment of Cardiology, First Affiliated Hospital of Harbin Medical University, No. 199 Dazhi Street, Harbin, Heilongjiang, 150001, China.
Huiying WangDepartment of Cardiology, First Affiliated Hospital of Harbin Medical University, No. 199 Dazhi Street, Harbin, Heilongjiang, 150001, China.
Yufeng BaiDepartment of Cardiology, First Affiliated Hospital of Harbin Medical University, No. 199 Dazhi Street, Harbin, Heilongjiang, 150001, China.
Dechao ZhaoDepartment of Cardiology, First Affiliated Hospital of Harbin Medical University, No. 199 Dazhi Street, Harbin, Heilongjiang, 150001, China. 003430@hrbmu.edu.cn.
Jinyu ChiDepartment of Cardiology, First Affiliated Hospital of Harbin Medical University, No. 199 Dazhi Street, Harbin, Heilongjiang, 150001, China. 005959@hrbmu.edu.cn.

Funding

National Natural Science Foundation of China 81570340National Science Foundation for Distinguished Young Scholars of China 81800352Postdoctoral Scientific Research Developmental Fund of Heilongjiang Province LBH-Q18093Young Medical Talents Funding Project of the First Affiliated Hospital of Harbin Medical University 2021J16
6 · The paper itself

Abstract

backgroundEstrogen deficiency is a major risk factor for postmenopausal hypertension. PDZK1, an estrogen-responsive scaffold protein, may interact with the β2-adrenergic receptor (β2-AR) to regulate vascular function, but this axis has not been characterized in the context of estrogen-deficient hypertension.

methodsWe used ovariectomized and PDZK1 knockout mice infused with angiotensin II to model hypertension in vivo, and HUVECs for mechanistic studies in vitro. Techniques included hemodynamic measurements, histology, molecular interaction assay, chromatin immunoprecipitation, and functional cellular assays.

resultsOvariectomy exacerbated Ang II-induced hypertension and vascular remodeling, which correlated with reduced PDZK1 expression. PDZK1 KO mice showed enhanced hypertensive responses and impaired endothelium-dependent relaxation. Mechanistically, PDZK1 interacted with β2-AR via its PDZ1 and PDZ4 domains, stabilizing β2-AR and activating the downstream ERK1/2/c-Fos pathway to promote endothelial proliferation. PDZK1 knockdown or β2-AR inhibition attenuated this signaling and suppressed endothelial repair.

conclusionOur study identifies a novel PDZK1/β2-AR/ERK1/2/c-Fos axis that is essential for maintaining endothelial function under estrogen-sufficient conditions. Disruption of this pathway in the context of estrogen deficiency contributes to hypertension, highlighting PDZK1 as a potential therapeutic target for postmenopausal hypertension.

Indexed as

HypertensionMAP Kinase Signaling SystemReceptors, Adrenergic, beta-2Angiotensin IIAnimalsDown-RegulationFemaleHumansHuman Umbilical Vein Endothelial CellsMembrane ProteinsMiceMice, Inbred C57BLMice, KnockoutOvariectomyProto-Oncogene Proteins c-fosSignal TransductionAngiotensin IIMembrane ProteinsPDZK1 protein, humanProto-Oncogene Proteins c-fosReceptors, Adrenergic, beta-2ERK1/2/c-Fos signaling pathwayEstrogen deficiencyHypertensionPDZK1β2-AR

Identifiers

PMID42458593
PMCPMC13656515

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.