Integrated analysis reveals ceRNA network of cardiac remodeling by SGLT2 inhibitor in middle-aged hypertensive rats

作者全名："Xiong, Tianhua; Jia, Yuewang; Tan, Fangyan; Long, Xianglin; Yuan, Xin; She, Qiang; Du, Jianlin"

作者地址："[Xiong, Tianhua; Jia, Yuewang; Long, Xianglin; She, Qiang; Du, Jianlin] Second Affiliated Hosp Chongqing Med Univ, Dept Cardiol, Chongqing, Peoples R China; [Tan, Fangyan; Yuan, Xin] Second Affiliated Hosp Chongqing Med Univ, Dept Neurosurg, Chongqing, Peoples R China"

通信作者："Du, JL (通讯作者)，Second Affiliated Hosp Chongqing Med Univ, Dept Cardiol, Chongqing, Peoples R China."

来源：BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:001155135100001

JCR分区：Q3

影响因子：2.5

年份：2024

卷号：696

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Sodium glucose cotransporter 2 inhibitors; Hypertension; Ventricular remodeling; Inflammation; Transcriptome

摘要："Sodium-glucose cotransporter 2 inhibitors (SGLT2i) represent an innovative class of antidiabetic agents that have demonstrated promise in mitigating cardiac remodeling. However, the transcriptional regulatory mechanisms underpinning their impact on blood pressure and the reversal of hypertension-induced cardiac remodeling remain largely unexplored. Given this context, our study concentrated on comparing the cardiac expression profiles of lncRNAs and mRNAs between Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). To validate our results, we performed blood pressure measurements, tissue staining, and qRT-PCR. The treatment led to a significant reduction in systolic blood pressure and improved cardiac remodeling by reducing myocardial fibrosis and regulating the inflammatory response. Our examination disclosed that ventricular tissue mRNA, regulated by hypertension, was primarily concentrated in the complement and coagulation cascades and cytokine-cytokine receptor interactions. Compared with SHR, the SGLT2i treatment group was associated with myocardial contraction. Investigation into the lncRNA-mRNA regulatory network and competing endogenous RNA (ceRNA) network suggested that the potential roles of these differentially expressed (DE) lncRNAs and mRNAs were tied to processes such as collagen fibril organization, inflammatory response, and extracellular matrix (ECM) modifications. We found that the expression of Col3a1, C1qa, and lncRNA NONRATT007139.2 were altered in the SHR group and that SGLT2i treatment reversed these changes. Our results suggest that dapagliflozin effectively reverses hypertension-induced myocardial remodeling through a lncRNA-mRNA transcriptional regulatory network, with immune cell-mediated ECM deposition as a potential regulatory target. This underlines the potentiality of SGLT2i and genes related to immunity as promising targets for the treatment of hypertension."

基金机构：National Natural Science Foundation of China (NSFC) [82270281]; Senior Medical Talents Program of Chongqing for Young and Middle-aged; Future Medicine Youth Innovation Team Development Support Program of Chongqing Medical University; Kuanren Talents Program of the Second Affiliated Hospital of Chongqing Medical University; [W0133]

基金资助正文："This work was supported by grants from the National Natural Science Foundation of China (NSFC) (82270281) , Senior Medical Talents Program of Chongqing for Young and Middle-aged (Jianlin Du [2022] ), Future Medicine Youth Innovation Team Development Support Program of Chongqing Medical University (W0133), Kuanren Talents Program of the Second Affiliated Hospital of Chongqing Medical University."