Quercetin attenuates angiotensin II-induced proliferation of vascular smooth muscle cells and p53 pathway activation in vitro and in vivo

Quercetin is an essential flavonoid mostly found in herbal Plants, fruits, and vegetables, which exhibits anti-hypertension properties. However, its pharmacological impact on angiotensin II (Ang II) induced the increase of blood pressure along with in-depth mechanism needs further exploration. The present study pointed out the anti-hypertensive role of quercetin and its comprehensive fundamental mechanisms. Our data showed that quercetin treatment substantially reduced the increase in blood pressure, pulse wave velocity, and aortic thickness of abdominal aorta in Ang II-infused C57BL/6 mice. RNA sequencing revealed that quercetin treatment reversed 464 differentially expressed transcripts in the abdominal aorta of Ang II-infused mice. Moreover, overlapping KEGG-enriched signaling pathways identified multiple common pathways between the comparison of Ang II versus control and Ang II + quercetin versus Ang II. Likewise, these pathways included cell cycle as well as p53 pathways. Transcriptome was further validated by immunohistochemistry, indicating that quercetin treatment significantly decreased the Ang II-induced expression of proliferating cell nuclear antigen (PCNA), cyclin-dependent kinase-4 (CDK4), and cyclin D1, while increased protein expression of p53, and p21 in abdominal aortic tissues of mice. In vitro, quercetin treatment meaningfully decreased the cell viability, arrested cell cycle at G0/G1 phase, and up-regulated the p53 and p21 proteins expression, as well as down-regulated the protein expression of cell cycle-related markers, for example, CDK4, cyclin D1 in Ang II stimulated vascular smooth muscle cells (VSMCs). This study addresses pharmacologic and mechanistic perspectives of quercetin against Ang-II-induced vascular injury and the increase of blood pressure.

angiotensin II; hypertension; p53 pathway; proliferation; quercetin.