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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Periprostatic adipose tissue thromboinflammation triggers prostatic neoplasia in early metabolic impairment: Interruption by rivaroxaban
Life Sciences, Volume 334, Article 122225, Year 2023
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Description
Aims: Prostate cancer is among the highest incidence malignancies in men with a prevalence rate increasing in parallel to the rising global trends in metabolic disorders. Whereas a sizeable body of evidence links metabolic impairment to negative prognosis of prostate cancer, the molecular mechanism underlying this connection has not been thoroughly examined. Our previous work showed that localized adipose tissue inflammation occurring in select adipose depots in early metabolic derangement instigated significant molecular, structural, and functional alterations in neighboring tissues underlying the complications observed at this stage. In this context, the periprostatic adipose tissue (PPAT) constitutes an understudied microenvironment with potential influence on the prostatic milieu. Main methods and results: We show that PPAT inflammation occurs in early prediabetes with signs of increased thrombogenic activity including enhanced expression and function of Factor X. This was mirrored by early neoplastic alterations in the prostate with fibrosis, increased epithelial thickness with marked luminal cellular proliferation and enhanced formation of intraepithelial neoplasia. Significantly, interruption of the procoagulant state in PPAT by a 10-day anticoagulant rivaroxaban treatment not only mitigated PPAT inflammation, but also reduced signs of prostatic neoplastic changes. Moreover, rivaroxaban decreased the murine PLum-AD epithelial prostatic cell viability, proliferation, migration, and colony forming capacity, while increasing oxidative stress. A protease-activated receptor-2 agonist reversed some of these effects. Significance: We provide some evidence of a molecular framework for the crosstalk between PPAT and prostatic tissue leading to early neoplastic changes in metabolic impairment mediated by upregulation of PPAT thromboinflammation. © 2023 Elsevier Inc.
Authors & Co-Authors
AlZaim, Ibrahim
Lebanon, Beirut
American University of Beirut
El-Nikhely, Nefertiti A.
Egypt, Alexandria
Alexandria University
Egypt, New Alamein
Alamein International University
Mougharbil, Nahed
Lebanon, Beirut
American University of Beirut
Darwiche, Nadine D.
Lebanon, Beirut
American University of Beirut
Abou-Kheir, Wassim G.
Lebanon, Beirut
American University of Beirut
El-Yazbi, Ahmed F.
Egypt, New Alamein
Alamein International University
Egypt, Alexandria
Alexandria University
Statistics
Authors: 6
Affiliations: 3
Identifiers
Doi:
10.1016/j.lfs.2023.122225
ISSN:
00243205
Research Areas
Cancer
Noncommunicable Diseases
Study Design
Cross Sectional Study
Cohort Study
Participants Gender
Male