Abstract
Arterial remodeling is a major pathological consequence of hypertension, which is recognized as the most common chronic non-communicable disease. However, the detailed mechanism of how arterial remodeling is induced by hypertension has not yet been fully elucidated. Evaluating the transcriptional changes in arterial tissue in response to elevated blood pressure at an early stage may provide new insights and identify novel therapeutic candidates in preventing arterial remodeling. Here, we used the ascending aorta of the transverse aortic constriction (TAC) model to induce arterial remodeling in C57BL/6 male mice. Age-matched mice were subjected to sham surgery as controls. The TAC model was only considered successful if the mice conformed to the criteria (RC/LC blood flow velocity with 5–10-fold change) 1 week after the surgery. Two weeks after surgery, the ascending aorta developed severe remodeling in TAC mice as compared to the sham group. High throughput sequencing was then applied to identify differentially expressed (DE) transcripts. In silicon analysis were then performed to systematically network transcriptional changes. A total of 1,019 mRNAs were significantly changed between TAC and the sham group at the transcriptional level. GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis revealed that stress/stimulus/immune-related biological processes played a crucial role during arterial remodeling. Our data provide a comprehensive understanding of global gene expression changes in the TAC model, which suggests that targeting inflammation and vascular smooth cell transformation are potential therapeutic strategies to interfere with the aortic remodeling at an early stage in the development of hypertension.
Highlights
Hypertension is the most prevalent chronic non-infectious disease and one of the most significant risk factors for cardiovascular and cerebrovascular diseases [1, 2]
The results indicated that Left ventricular systolic pressure (LVSP) in the transverse aortic constriction (TAC) group was significantly higher than the sham group (Supplementary Figures 2A,B)
The KEGG analysis was further performed in the top 200 upregulated and top 200 down-regulated differentially expressed genes (DEGs), and the results showed that the major enrichment pathways were extracellular matrix (ECM)-receptor interactions (e.g., Itga2b, Tnn, Thbs1, and Itga11), complement and coagulation cascades (e.g., Fgg, C7, A2m, and Gpx1) and vascular smooth muscle contraction (e.g., Pla2g5, Myh11, Myl6, FIGURE 2 | Transcriptional changes in TAC models. (A) An overview of DEGs in TAC models; (B) Volcano plot illustrating DEGs between the TAC and sham groups
Summary
Hypertension is the most prevalent chronic non-infectious disease and one of the most significant risk factors for cardiovascular and cerebrovascular diseases [1, 2]. The World Health Organization estimates that more than 1.13 billion people worldwide suffer from high blood pressure. Due to the aging population, the number of hypertension patients is expected to be Transcriptional Variation in Aortic Remodeling over 1.5 billion by 2025 globally [3]. The increasing burden of hypertension enhances the morbidity and mortality of cardiovascular and kidney diseases, it causes increasing economic costs that affect the whole society [4]. Clinical anti-hypertensive drugs, including ACEI, ARB, and βblockers, have certain functions in inhibiting vascular remodeling while reducing blood pressure, the clinical benefits of these drugs are not satisfactory [5]. There is high demand and an urgent need to uncover new therapeutic targets for hypertension therapies
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