Endothelial to mesenchymal transition contributes to nicotine-induced atherosclerosis

Qin, Wei; Zhang, Longyin; Li, Zhange; Xiao, Dan; Zhang, Yue; Zhang, Haiying; Mokembo, Justine Nyakango; Monayo, Seth Mikaye; Jha, Nabanit Kumar; Kopylov, F. Yu.; Shchekochikhin, Dmitri; Zhang, Yong

doi:10.7150/thno.42470

Cited by 28 publications

(14 citation statements)

References 71 publications

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“…Moreover, nicotine promotes atherosclerosis by enhancing EndMT via activation of ERK1/2. Blocking ERK1/2 with inhibitor efficiently preserves endothelial phenotype upon nicotine stimulation 53 . However, in our study we determined U0126 had little effect on cell apoptosis both in vitro and in vivo ( Figure S6 , S7).…”

Section: Discussionmentioning

confidence: 99%

ERK1/2 inhibition reduces vascular calcification by activating miR-126-3p-DKK1/LRP6 pathway

et al. 2021

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Rationale : Vascular microcalcification increases the risk of rupture of vulnerable atherosclerotic lesions. Inhibition of ERK1/2 reduces atherosclerosis in animal models while its role in vascular calcification and the underlying mechanisms remains incompletely understood. Methods: Levels of activated ERK1/2, DKK1, LRP6 and BMP2 in human calcific aortic valves were determined. ApoE deficient mice received ERK1/2 inhibitor (U0126) treatment, followed by determination of atherosclerosis, calcification and miR-126-3p production. C57BL/6J mice were used to determine the effect of U0126 on Vitamin D 3 (VD 3 )-induced medial arterial calcification. HUVECs, HAECs and HASMCs were used to determine the effects of ERK1/2 inhibitor or siRNA on SMC calcification and the involved mechanisms. Results : We observed the calcification in human aortic valves was positively correlated to ERK1/2 activity. At cellular and animal levels, U0126 reduced intimal calcification in atherosclerotic lesions of high-fat diet-fed apoE deficient mice, medial arterial calcification in VD 3 -treated C57BL/6J mice, and calcification in cultured SMCs and arterial rings. The reduction of calcification was attributed to ERK1/2 inhibition-reduced expression of ALP, BMP2 and RUNX2 by activating DKK1 and LRP6 expression, and consequently inactivating both canonical and non-canonical Wnt signaling pathways in SMCs. Furthermore, we determined ERK1/2 inhibition activated miR-126-3p production by facilitating its maturation through activation of AMPKα-mediated p53 phosphorylation, and the activated miR-126-3p from ECs and SMCs played a key role in anti-vascular calcification actions of ERK1/2 inhibition. Conclusions : Our study demonstrates that activation of miR-126-3p production in ECs/SMCs and interactions between ECs and SMCs play an important role in reduction of vascular calcification by ERK1/2 inhibition.

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Section: Discussionmentioning

confidence: 99%

ERK1/2 inhibition reduces vascular calcification by activating miR-126-3p-DKK1/LRP6 pathway

et al. 2021

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“…Smoking can regulate ECs, VSMCs and mononuclear macrophages through a variety of mechanisms to participate in the occurrence and development of atherosclerosis (Table 1). However, in vivo experiments, many studies have also confirmed the relationship between smoking and atherosclerosis in animals (138,139). Currently, the animal models used to study atherosclerosis mainly include ApoE-/-mice, LDLR-/-mice, and ApoE-/-and LDLR-/-mice.…”

Section: Smoking and Animal Models Of Atherosclerosismentioning

confidence: 99%

Smoking and the Pathophysiology of Peripheral Artery Disease

Wang

Zhao

Geng

et al. 2021

Front. Cardiovasc. Med.

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Smoking is one of the most important preventable factors causing peripheral artery disease (PAD). The purpose of this review is to comprehensively analyze and summarize the pathogenesis and clinical characteristics of smoking in PAD based on existing clinical, in vivo, and in vitro studies. Extensive searches and literature reviews have shown that a large amount of data exists on the pathological process underlying the effects of cigarette smoke and its components on PAD through various mechanisms. Cigarette smoke extracts (CSE) induce endothelial cell dysfunction, smooth muscle cell remodeling and macrophage phenotypic transformation through multiple molecular mechanisms. These pathological changes are the molecular basis for the occurrence and development of peripheral vascular diseases. With few discussions on the topic, we will summarize recent insights into the effect of smoking on regulating PAD through multiple pathways and its possible pathogenic mechanism.

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“…Regarding dose selection of nicotine, it ranges from 0.6 to 2 mg/kg/day that mainly depending upon the frequency of administration and the duration of the study (2-4 weeks; Table IV). Additionally, it also depends upon the species that have been included in the study as Apo E-/-mice established vascular endothelial dysfunction within 12 weeks of orally administering low dose of nicotine (0.1 mg/mL) (Qin et al, 2020). Though a high dose is used for the shorter duration studies, a high dose is associated with mortality.…”

Section: Nicotine-inducedmentioning

confidence: 99%

Experimental models for vascular endothelial dysfunction

.¹,

Gupta²,

Tomar

et al. 2021

Bangladesh J Pharmacol

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Vascular endothelial dysfunction is characterized by apoptosis of endothelial cells, an imbalance between vasoconstrictory and vasodilatory substances, the imbalance between ROS and antioxidants, vascular remodeling, loss of vascular integrity which leads to an increased risk of cardiovascular complications. To date, no therapeutic intervention is available as a promising agent. This may be due to a poor understanding of the underlying mechanism involved in vascular endothelial dysfunction in the pathogenesis. Animal models sharing identical features as that of humans are paramount to understand fundamental physiology, mechanism and to explore new targets for developing therapeutic agents. Thus, it becomes mandatory to re-explore the available animal models for a better understanding of molecular pathways involving vascular endothelial dysfunction. The purpose of this paper is to review different models for vascular endothelial dysfunction to the outlook for developing new drugs to treat vascular endothelial dysfunction.

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Endothelial to mesenchymal transition contributes to nicotine-induced atherosclerosis

Cited by 28 publications

References 71 publications

ERK1/2 inhibition reduces vascular calcification by activating miR-126-3p-DKK1/LRP6 pathway

ERK1/2 inhibition reduces vascular calcification by activating miR-126-3p-DKK1/LRP6 pathway

Smoking and the Pathophysiology of Peripheral Artery Disease

Experimental models for vascular endothelial dysfunction

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