Kaempferol Alleviates Angiotensin II-Induced Cardiac Dysfunction and Interstitial Fibrosis in Mice

Liu, Yuan; Gao, Lu; Guo, Sen; Liu, Yuzhou; Zhao, Xiaoyan; Li, Ran; Yan, Xiaofei; Liu, Yunpeng; Wang, Shuai; Niu, Xiaoyu; Yao, Liantao; Zhang, Yanzhou; Li, Ling; Yang, Haibo

doi:10.1159/000484304

Cited by 48 publications

(39 citation statements)

References 32 publications

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“…Aging increases TGF‐ß expression, which plays an important role in the synthesis and secretion of collagen by cardiac fibroblasts, thus contributing to cardiac stiffening (Nakou et al, ). Kaempferol and PC of a yacon plant were shown to alleviate, respectively, myocardial fibrosis in angiotensin II‐induced cardiac dysfunction and in diabetic rat model (Dos Santos et al, ; Liu et al, ). Nevertheless, these experiments were undergone in pathological conditions not related to normal aging.…”

Section: Discussionmentioning

confidence: 99%

Long‐term intake of phenolic compounds attenuates age‐related cardiac remodeling

et al. 2019

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With the onset of advanced age, cardiac‐associated pathologies have increased in prevalence. The hallmarks of cardiac aging include cardiomyocyte senescence, fibroblast proliferation, inflammation, and hypertrophy. The imbalance between levels of reactive oxygen species (ROS) and antioxidant enzymes is greatly enhanced in aging cells, promoting cardiac remodeling. In this work, we studied the long‐term impact of phenolic compounds (PC) on age‐associated cardiac remodeling. Three‐month‐old Wistar rats were treated for 14 months till middle‐age with either 2.5, 5, 10, or 20 mg kg−1 day−1 of PC. PC treatment showed a dose‐dependent preservation of cardiac ejection fraction and fractional shortening as well as decreased hypertrophy reflected by left ventricular chamber diameter and posterior wall thickness as compared to untreated middle‐aged control animals. Analyses of proteins from cardiac tissue showed that PC attenuated several hypertrophic pathways including calcineurin/nuclear factor of activated T cells (NFATc3), calcium/calmodulin‐dependent kinase II (CAMKII), extracellular regulated kinase 1/2 (ERK1/2), and glycogen synthase kinase 3ß (GSK 3ß). PC‐treated groups exhibited reduced plasma inflammatory and fibrotic markers and revealed as well ameliorated extracellular matrix remodeling and interstitial inflammation by a downregulated p38 pathway. Myocardia from PC‐treated middle‐aged rats presented less fibrosis with suppression of profibrotic transforming growth factor‐ß1 (TGF‐ß1) Smad pathway. Additionally, reduction of apoptosis and oxidative damage in the PC‐treated groups was reflected by elevated antioxidant enzymes and reduced RNA/DNA damage markers. Our findings pinpoint that a daily consumption of phenolic compounds could preserve the heart from the detrimental effects of aging storm.

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Section: Discussionmentioning

confidence: 99%

Long‐term intake of phenolic compounds attenuates age‐related cardiac remodeling

et al. 2019

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“…Cardiac fibrosis is a major feature of hypertrophic cardiomyopathy and contributes to ventricular dysfunction and life-threatening arrhythmia [13,24]. Our in vivo study showed that Hyp treatment reduced the pressure overload-induced fibrotic response.…”

Section: Discussionmentioning

confidence: 51%

Hyperoside Protects Against Pressure Overload-Induced Cardiac Remodeling via the AKT Signaling Pathway

Wang

Liu

Xiao

et al. 2018

Cell Physiol Biochem

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Background/Aims: Cardiac hypertrophy is a major predisposing factor for heart failure and sudden cardiac death. Hyperoside (Hyp), a flavonoid isolated from Rhododendron ponticum L., is a primary component of Chinese traditional patent medicines. Numerous studies have shown that Hyp exerts marked anti-viral, anti-inflammatory, anti-oxidant, anti-cancer, anti-ischemic, and particularly cardio-protective effects. However, the effects of Hyp on cardiac hypertrophy have not been explored. The aims of this study were to determine whether Hyp could protect against cardiac remodeling and to clarify the potential molecular mechanisms. Methods: Neonatal rat cardiac myocytes were isolated and treated with different concentrations of Hyp, then cultured with angiotensin II for 48 h. Mice were subjected to either aortic banding or sham surgery (control group). One week after surgery, the mice were treated with Hyp (20 mg/kg/day) or vehicle by oral gavage for 7 weeks. Hypertrophy was evaluated by assessing morphological changes, echocardiographic parameters, histology, and biomarkers. Results: Hyp pretreatment suppressed angiotensin II-induced hypertrophy in cardiomyocytes. Hyp exerted no basal effects but attenuated cardiac hypertrophy and dysfunction, fibrosis, inflammation, and oxidative stress induced by pressure overload. Both in vivo and in vitro experiments demonstrated that the effect of Hyp on cardiac hypertrophy was mediated by blocking activation of the AKT signaling pathway. Conclusion: Hyp improves cardiac function and prevents the development of cardiac hypertrophy via AKT signaling. Our results suggest a protective effect of Hyp on pressure overload-induced cardiac remodeling. Taken together, Hyp may have a role in the pharmacological therapy of cardiac hypertrophy.

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“…Afterwards, they adopted endothelial lineage tracing and observed the emergence of fibroblasts derived from EndMT in the process of kidney fibrosis s [27]. Interestingly, extensive research has attested that TGF-β signaling is potentially involved in the stimulation of EndMT [4, 9, 28]. Xavier et al utilized heterozygous endothelium-specific TGF-β receptor knockout mice and supported that ablating TGF-β signaling is sufficient to curtail EndMT and thereby attenuate the fibrotic responses in injured kidney [29].…”

Section: Discussionmentioning

confidence: 99%

Pioglitazone Alleviates Cardiac Fibrosis and Inhibits Endothelial to Mesenchymal Transition Induced by Pressure Overload

Wei

Zhang

et al. 2017

Cell Physiol Biochem

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Background/Aims: Cardiac fibrosis, characterized by an unbalanced production and degradation of extracellular matrix components, is a common pathophysiology of multiple cardiovascular diseases. Recent studies suggested that endothelial to mesenchymal transition (EndMT) could be a source of activated fibroblasts and contribute to cardiac fibrosis. Here, the role of pioglitazone (PIO) in cardiac fibrosis and EndMT was elaborated. Methods: Male C57BL/6 mice were subjected to aortic banding (AB), which was used to construct a model of pressure overload-induced cardiac hypertrophy. PIO and GW9662 was given for 4 weeks to detect the effects of PIO on EndMT. Results: Our results showed PIO treatment attenuated cardiac hypertrophy, dysfunction and fibrosis response to pressure overload. Mechanistically, PIO suppressed the TGF-β/Smad signaling pathway activated by 4-week AB surgery. Moreover, PIO dramatically inhibited EndMT in vivo and in vitro stimulated by pressure overload or TGF-β. A selective antagonist of PPAR-γ, GW9662, neutralized the anti-fibrotic effect and abolished the inhibitory effect of EndMT during the treatment of PIO. Conclusion: Our data implied that PIO exerts an alleviative effect on cardiac fibrosis via inhibition of the TGF-β/Smad signaling pathway and EndMT by activating PPAR-γ.

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Kaempferol Alleviates Angiotensin II-Induced Cardiac Dysfunction and Interstitial Fibrosis in Mice

Cited by 48 publications

References 32 publications

Long‐term intake of phenolic compounds attenuates age‐related cardiac remodeling

Long‐term intake of phenolic compounds attenuates age‐related cardiac remodeling

Hyperoside Protects Against Pressure Overload-Induced Cardiac Remodeling via the AKT Signaling Pathway

Pioglitazone Alleviates Cardiac Fibrosis and Inhibits Endothelial to Mesenchymal Transition Induced by Pressure Overload

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