Tiaopi huxin recipe improved endothelial dysfunction and attenuated atherosclerosis by decreasing the expression of caveolin‐1 in ApoE‐deficient mice

Abstract

The Tiaopi Huxin recipe (TPHXR) is widely used in traditional Chinese medicine for the clinical treatment of coronary heart disease. However, the mechanism of TPHXR treatment of atherosclerosis (AS) has not been fully elucidated. In this study, we have aimed to explore the potential antiatherosclerotic effect of TPHXR and its underlying mechanisms. Male ApoE knockout (ApoE−/−) mice were fed a high‐fat diet for 12 weeks and were randomly divided into four groups: the control group, and the low‐dose, medium‐dose, and high‐dose TPHXR groups. The nitric oxide (NO) levels in arterial tissue and human umbilical vein endothelial cells (HUVECs) were measured by diaminofluorescein‐2 diacetate staining. Vasorelaxation of mice aorta was performed by wire myograph. Inflammatory cytokines, including tumor necrosis factor‐α (TNF‐α), hs‐CRP, IL‐6, and IL‐1β, in mice plasma were analyzed by enzyme‐linked immunosorbent assay. Western blot analysis was applied to observe protein expression. Oil Red O staining was utilized for the quantification of atherosclerotic plaques. Results showed that 4 weeks of high‐ and medium‐dose TPHXR treatment by oral gavage reduced atheromatous lesions in ApoE −/− mice. The high‐ and medium‐dose TPHXR treatment, but not the low‐dose treatment, promoted eNOS phosphorylation, increased NO levels and improved endothelium‐dependent vasorelaxation in ApoE −/− mice. High‐ and medium‐dose TPHXR, but not low‐dose TPHXR, decreased the expression of cav‐1, NF‐κB p50, NF‐κB p65, ICAM1, VCAM‐1, TNF‐α, IL‐6, and IL‐1β in the vasculature of ApoE −/− mice. Enzyme‐linked immunosorbent assay analysis indicated that high‐ and medium‐dose TPHXR decreased the levels of TNF‐α, IL‐6, hs‐CRP, and IL‐1β. In conclusion, our findings show that TPHXR improved the endothelial function and reduced atheromatous lesions in ApoE −/− mice. This result may be due to the decreased expression of caveolin‐1 and NF‐κB and, hence, the attenuated inflammatory response in AS mice vasculature. TPHXR may represent a promising intervention in patients with AS.

Improvement of Endothelial Dysfunction of Berberine in Atherosclerotic Mice and Mechanism Exploring through TMT-Based Proteomics

“…Improving endotheliumdependent vasodilatation and restoring endothelial function in patients with atherosclerosis may prevent cardiovascular events [30]. In addition, preventing impairment of endothelium-dependent relaxation was found to attenuate atherosclerosis in ApoE -/mice [31]. Our results revealed impaired endothelium-dependent vasodilatation induced by ACh in ApoE -/mice fed a western-type diet, suggesting endothelial dysfunction in ApoE -/mice.…”

Caveolin as a Novel Potential Therapeutic Target in Cardiac and Vascular Diseases: A Mini Review

“…Further, compared to that in ApoE −/− mice, caveolin-1 −/− ApoE −/− mice showed reduced endothelial activation and reduced VCAM-1 expression in the aorta, which was partly due to the disruptions in the transfer and accumulation of LDL in the arterial wall [18]. Moreover, the inhibition of caveolin-1 results in the attenuation of atherosclerotic lesions in ApoE −/− mice, which is associated with decreased NF-kB-mediated inflammation [19]. Furthermore, caveolae have also been reported to regulate ROS production through NADPH oxidase (Nox) by modulating oxidative stress and ox-LDL-induced cellular senescence in the vasculature [4,20].…”

“…Traditional Chinese herbal medicines have been shown to be beneficial for the treatment of cardiovascular diseases by targeting caveolin. The Tiaopi Huxin recipe, a traditional Chinese medicine widely used to treat coronary heart disease, was recently shown to decrease the expression of caveolin-1, thereby improving endothelial function and reducing atheromatous lesions in ApoE −/− mice [19]. Further, Yan et al [89] showed that Zhuanggu Jianxi Decoction, a traditional Chinese medicine, inhibits IL-1β-induced activation of the caveolin-p38MAPK pathway, thereby suppressing the inflammatory response.…”

Long non-coding RNA NEAT1 inhibits oxidative stress-induced vascular endothelial cell injury by activating the miR-181d-5p/CDKN3 axis

“…The pathogenesis of AS progresses with EC dysfunction [26,27]. It is known that oxidative stress causes endothelial Figure 3.…”