Inhibitory effects of doxycycline on the onset and progression of abdominal aortic aneurysm and its related mechanisms

Yu, Maomao; Chen, Cong; Cao, Yini; Qi, Rong

doi:10.1016/j.ejphar.2017.05.041

Cited by 28 publications

(30 citation statements)

References 41 publications

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“…Zeydanli et al reported that doxycycline ameliorated vascular endothelial and contractile dysfunction in thoracic aorta by inhibiting oxidative stress and up-regulation of gelatinases in diabetic rats. 21 Recently, inhibitory effects of doxycycline in mice model of abdominal aortic aneurysm (AAA) were attributed to antioxidant and MMP inhibitory effects of this agent. 33 Similarly in a clinical study, doxycycline treatment was shown to cause higher plasma levels of TIMP-2 which, in turn, inversely correlate with 6-month infarct size and severity as well as LV remodelling.…”

Section: Discussionmentioning

confidence: 99%

<p>Low-dose doxycycline inhibits hydrogen peroxide-induced oxidative stress, MMP-2 up-regulation and contractile dysfunction in human saphenous vein grafts</p>

Saeed

Arun

Guzeloglu³

et al. 2019

DDDT

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Background: Cardiopulmonary bypass (CPB) applied during coronary artery bypass grafting (CABG), promotes inflammation, generation of reactive oxygen species (ROS) and up-regulation of matrix metalloproteinases (MMPs). All these complications may lead to contractile dysfunction, restenosis and early graft failure, restricting long-term efficacy of bypass grafts. Low-dose doxycycline is a potent MMP inhibitor and ROS scavenger. In this study, we aimed to investigate the effects of doxycycline on ROS generation, MMP regulation and contractile dysfunction induced by H 2 O 2 in human saphenous vein (HSV) grafts. Methods: HSV grafts (n=7) were divided into four groups after removing endothelial layer by mechanical scratching and incubated with 10 µM H 2 O 2 and/or 10 µM doxycycline for 16 hrs. Untreated segments served as control. Concentration–response curves to noradrenaline (NA), potassium chloride (KCl), serotonin (5-HT) and papaverine were performed. Superoxide anion and other ROS levels were determined by using lucigenin- and luminol-enhanced chemiluminescence assays, respectively. Expression/activity of gelatinases (MMP-2/MMP-9) was examined by gelatin zymography. MMP-13 expression was evaluated by immunostaining/immunoscoring. Results: H 2 O 2 incubation increased superoxide anion and other ROS levels. Doxycycline prevented these increments. H 2 O 2 suppressed contractile responses to NA, KCl and 5-HT. Doxycycline ameliorated contractions to NA and KCl but not to 5-HT. H 2 O 2 or doxycycline did not altered relaxation to papaverine. MMP-2 and MMP-13 expression increased with H 2 O 2 , but doxycycline inhibited MMP-2 up-regulation/activation. Conclusion: Low-dose doxycycline may have beneficial effects on increased oxidative stress, MMP up-regulation/activation and contractile dysfunction in HSV grafts.

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Section: Discussionmentioning

confidence: 99%

<p>Low-dose doxycycline inhibits hydrogen peroxide-induced oxidative stress, MMP-2 up-regulation and contractile dysfunction in human saphenous vein grafts</p>

Saeed

Arun

Guzeloglu³

et al. 2019

DDDT

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“…MMPs released by macrophages damage elastic fibers and ECM, followed by more inflammatory cell recruitment to the injured site, which forms a vicious circle and eventually leads to either dilatation or rupture of AAA [36][37][38]. erefore, it is important to explore novel anti-inflammatory drugs that have been used in clinical AAA therapy [39][40][41].…”

Section: Discussionmentioning

confidence: 99%

Chemerin-9 Attenuates Experimental Abdominal Aortic Aneurysm Formation in ApoE−/− Mice

Chen

Han

Bian

et al. 2021

Journal of Oncology

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Chronic inflammation plays an essential role in the pathogenesis of abdominal aortic aneurysm (AAA), a progressive segmental abdominal aortic dilation. Chemerin, a multifunctional adipocytokine, is mainly generated in the liver and adipose tissue. The combination of chemerin and chemokine-like receptor 1 (CMKLR1) has been demonstrated to promote the progression of atherosclerosis, arthritis diseases, and Crohn’s disease. However, chemerin-9 acts as an analog of chemerin to exert an anti-inflammatory effect by binding to CMKLR1. Here, we first demonstrated that AAA exhibited higher levels of chemerin and CMKLR1 expression compared with the normal aortic tissues. Hence, we hypothesized that the chemerin/CMKLR1 axis might be involved in AAA progression. Moreover, we found that chemerin-9 treatment markedly suppressed inflammatory cell infiltration, neovascularization, and matrix metalloproteinase (MMP) expression, while increasing the elastic fibers and smooth muscle cells (SMCs) in Ang II-induced AAA in ApoE−/− mice. This demonstrated that chemerin-9 could inhibit AAA formation. Collectively, our findings indicate a potential mechanism underlying AAA progression and suggest that chemerin-9 can be used therapeutically.

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“…In an angiotensin II-induced AAA model, doxycycline markedly reduced the incidence and severity of AAA [66]. Doxycycline also had a preventive and therapeutic effect on AAA in a mouse elastase-induced AAA model, in part, interestingly, through upregulating HO-1 expression [67]. In a prospective, double-blind, randomized, placebo-controlled study, doxycycline significantly decreased the expansion rate of AAA [68].…”

Section: Ho-1 In Abdominal Aortic Aneurysmmentioning

confidence: 92%

Therapeutic Potential of Heme Oxygenase-1 in Aneurysmal Diseases

et al. 2020

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Abdominal aortic aneurysm (AAA) and intracranial aneurysm (IA) are serious arterial diseases in the aorta and brain, respectively. AAA and IA are associated with old age in males and females, respectively, and if rupture occurs, they carry high morbidity and mortality. Aneurysmal subarachnoid hemorrhage (SAH) due to IA rupture has a high rate of complication and fatality. Despite these severe clinical outcomes, preventing or treating these devastating diseases remains an unmet medical need. Inflammation and oxidative stress are shared pathologies of these vascular diseases. Therefore, therapeutic strategies have focused on reducing inflammation and reactive oxygen species levels. Interestingly, in response to cellular stress, the inducible heme oxygenase-1 (HO-1) is highly upregulated and protects against tissue injury. HO-1 degrades the prooxidant heme and generates molecules with antioxidative and anti-inflammatory properties, resulting in decreased oxidative stress and inflammation. Therefore, increasing HO-1 activity is an attractive option for therapy. Several HO-1 inducers have been identified and tested in animal models for preventing or alleviating AAA, IA, and SAH. However, clinical trials have shown conflicting results. Further research and the development of highly selective HO-1 regulators may be needed to prevent the initiation and progression of AAA, IA, or SAH.

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Inhibitory effects of doxycycline on the onset and progression of abdominal aortic aneurysm and its related mechanisms

Cited by 28 publications

References 41 publications

<p>Low-dose doxycycline inhibits hydrogen peroxide-induced oxidative stress, MMP-2 up-regulation and contractile dysfunction in human saphenous vein grafts</p>

<p>Low-dose doxycycline inhibits hydrogen peroxide-induced oxidative stress, MMP-2 up-regulation and contractile dysfunction in human saphenous vein grafts</p>

Chemerin-9 Attenuates Experimental Abdominal Aortic Aneurysm Formation in ApoE−/− Mice

Therapeutic Potential of Heme Oxygenase-1 in Aneurysmal Diseases

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