Dihydrotanshinone I Attenuates Atherosclerosis in ApoE-Deficient Mice: Role of NOX4/NF-κB Mediated Lectin-Like Oxidized LDL Receptor-1 (LOX-1) of the Endothelium

Metabolic syndrome is a critically important precursor to the onset of many diseases, such as cardiovascular disease, and cardiovascular disease is the leading cause of death worldwide. The primary risk factors of metabolic syndrome include hyperglycaemia, abdominal obesity, dyslipidaemia, and high blood pressure. It has been well documented that metabolic syndrome alters vascular endothelial and smooth muscle cell functions in the heart, brain, kidney and peripheral vessels. However, there is less information available regarding how metabolic syndrome can affect pulmonary vascular function and ultimately increase an individual's risk of developing various pulmonary vascular diseases, such as pulmonary hypertension. Here, we review in detail how metabolic syndrome affects pulmonary vascular function.

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“…), and overexpress LOX‐1 in ECs (Zhao et al . ). This pro‐inflammatory predisposition might exaggerate the damage of an acute lung injury.…”

Section: Vascular Function In Dyslipidaemiamentioning

confidence: 97%

Pulmonary vascular dysfunction in metabolic syndrome

Willson

Watanabe

Tsuji‐Hosokawa

2018

The Journal of Physiology

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“…A recent study [88] from Chen's laboratory has shown that dihydrotanshinone attenuates diet-induced atherosclerosis in ApoE -/mice. The underlying mechanism is related to blockade of the NOX4 (NADPH oxidase 4)/ROS (reactive oxygen species)/NF-κB/LOX-1 signaling pathway in LPS-stimulated human endothelial cells and subsequent oxLDL endocytosis and monocyte adhesion to endothelial cells [88] . Dihydrotanshinone also inhibits proliferation, migration and tube formation in endothelial cells, thereby inhibiting angiogenesis [89] .…”

Section: Dihydrotanshinonementioning

confidence: 99%

Salvia miltiorrhizaBurge (Danshen): a golden herbal medicine in cardiovascular therapeutics

2018

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Salvia miltiorrhiza Burge (Danshen) is an eminent medicinal herb that possesses broad cardiovascular and cerebrovascular protective actions and has been used in Asian countries for many centuries. Accumulating evidence suggests that Danshen and its components prevent vascular diseases, in particular, atherosclerosis and cardiac diseases, including myocardial infarction, myocardial ischemia/reperfusion injury, arrhythmia, cardiac hypertrophy and cardiac fibrosis. The published literature indicates that lipophilic constituents (tanshinone I, tanshinone IIa, tanshinone IIb, cryptotanshinone, dihydrotanshinone, etc) as well as hydrophilic constituents (danshensu, salvianolic acid A and B, protocatechuic aldehyde, etc) contribute to the cardiovascular protective actions of Danshen, suggesting a potential synergism among these constituents. Herein, we provide a systematic up-to-date review on the cardiovascular actions and therapeutic potential of major pharmacologically active constituents of Danshen. These bioactive compounds will serve as excellent drug candidates in small-molecule cardiovascular drug discovery. This article also provides a scientific rationale for understanding the traditional use of Danshen in cardiovascular therapeutics.

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“… 41 reported that blockade of TNF-α-induced ROS by NOX4 siRNA suppressed the TNF-α-induced ICAM-1 expression and subsequent monocyte adhesion to human aortic endothelial cells. Also our previous study showed that NOX4 plays an important role in the process of atherosclerosis 42 . In the current research, we found that the knockdown of NOX4 by siRNA significantly inhibited the TNF-α-induced ROS production and ICAM-1 expression at both protein and mRNA levels, as well as the THP-1 – HUVEC adhesions.…”

Section: Discussionmentioning

confidence: 91%

Danshenol A inhibits TNF-α-induced expression of intercellular adhesion molecule-1 (ICAM-1) mediated by NOX4 in endothelial cells

Zhao

Feng

Guo

et al. 2017

Sci Rep

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ICAM-1 overexpression and subsequent adhesion of leukocytes to endothelial cells play critical roles in the early stage of atherosclerosis. Danshenol A (DA) is an abietane-type diterpenoid isolated from traditional Chinese herb Salvia miltiorrhiza Bunge. The mechanisms under its regulation of adhesion of molecular expression are explored. Here, the effect of DA on TNF-α-induced ICAM-1 expression was investigated in endothelial cells. TNF-α-induced ICAM-1 expression and subsequent adhesion of monocytes, as well as elevated reactive oxygen species (ROS) generation and NOX4 expression were all significantly reversed by DA, siNOX4 and NOX4 inhibitor GKT137831. Furthermore, TNF-α-induced ICAM-1 expression, which was increased via IKKβ/IκBα-mediated activation of NF-κB p65, was also inhibited by DA. Interestingly, NOX4 overexpression suppressed the ICAM-1 expression, and this finding may be ascribed to the activation of Nrf-2. Additionally, NF-κB inhibitor PDTC, siNOX4, or DA can decrease the TNF-α-induced ICAM-1 expression and suppress the adhesion of monocytes. In all, DA inhibited TNF-α-induced ICAM-1 expression and subsequent monocyte adhesion to endothelial cells through the NOX4-dependent IKKβ/NF-κB pathway. Besides, NOX4 played dual role in regulating ICAM-1 expression via diverse signal pathway. This novel bioactivity will make DA a good candidate to be further explored for therapeutic or preventive application for atherosclerosis.

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Dihydrotanshinone I Attenuates Atherosclerosis in ApoE-Deficient Mice: Role of NOX4/NF-κB Mediated Lectin-Like Oxidized LDL Receptor-1 (LOX-1) of the Endothelium

Cited by 45 publications

References 53 publications

Pulmonary vascular dysfunction in metabolic syndrome

Pulmonary vascular dysfunction in metabolic syndrome

Salvia miltiorrhizaBurge (Danshen): a golden herbal medicine in cardiovascular therapeutics

Danshenol A inhibits TNF-α-induced expression of intercellular adhesion molecule-1 (ICAM-1) mediated by NOX4 in endothelial cells

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