Effects of Losartan on expression of connexins at the early stage of atherosclerosis in rabbits

Ruan, Li-Ming; Cai, Wei; Chen, Jun-zhu; Duan, Jin-feng

doi:10.7150/ijms.7.82

Cited by 5 publications

(4 citation statements)

References 16 publications

(19 reference statements)

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“…Connexin-43 is a member of the connexin family, which forms intercellular gap junctions and is closely associated with inflammation. Connexin-43-knockdown alleviates the brain inflammation and glia activation induced by peripheral lipopolysaccharide injection ( 38 ). Connexin-43 is upregulated in the neointimal SMCs at an early stage of atherosclerosis in rabbits ( 39 ).…”

Section: Discussionmentioning

confidence: 99%

Establishment of an interleukin-1β-induced inflammation-activated endothelial cell-smooth muscle cell-mononuclear cell co-culture model and evaluation of the anti-inflammatory effects of tanshinone IIA on atherosclerosis

Guo

Chen

et al. 2015

Molecular Medicine Reports

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Increasing evidence supports the hypothesis that inflammatory reactions serves an important function in the formation, progression and plaque rupture of atherosclerosis. Interleukin (IL)-1 primarily induces inflammation and is closely associated with the inflammatory environment and the formation of atherosclerosis. The present study aimed to establish an in vitro model for the evaluation of drug efficacy in the intervention of atherosclerosis from the inflammatory perspective, and to observe the anti-inflammatory effects of tanshinone IIA and andrographolide on atherosclerosis. The IL-1β-induced inflammation-activated endothelial cell (EC)-smooth muscle cell (SMC)-mononuclear cell (MC) co-culture model was established, based on the changes in a series of atherosclerosis-associated inflammatory markers secreted by ECs and SMCs. The expression of connexin in ECs, adhesion of MCs and changes in inflammatory signalling molecules were selected as evaluation indices for the inflammatory microenvironment of atherosclerosis. The use of this model revealed that tanshinone IIA exhibited significant efficacy against atherosclerosis and its inflammatory reactions. Inflammatory reactions were regarded as the primary mechanism underlying atherosclerosis. The established model simulated a series of relevant changes in the arterial wall under the inflammatory cytokines with oxidized low-density lipoprotein during the atherosclerotic process. The present study presented a reliable method for the identification of drugs with potential anti-inflammatory activity in atherosclerosis, for investigating the mechanisms of action, considering the improvement of the inflammatory state and the increase in plaque stability observed.

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Section: Discussionmentioning

confidence: 99%

Establishment of an interleukin-1β-induced inflammation-activated endothelial cell-smooth muscle cell-mononuclear cell co-culture model and evaluation of the anti-inflammatory effects of tanshinone IIA on atherosclerosis

Guo

Chen

et al. 2015

Molecular Medicine Reports

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“…During the migration and proliferation of arterial SMCs, GJ transforms from the contractile phenotype to the synthetic phenotype. Recently, it has been shown that Cx43 expression is markedly enhanced in cultured SMCs at synthetic state when compared with that in those at the contractile state (Yeh et al, 1997;Song et al, 2009), and relatively high expression of Cx43 was observed in migrating and proliferating SMCs in the neointima following balloon injury (Ruan et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

Effects of Losartan and Ramipril on the connexin expression in a rabbit balloon injury model

Li¹,

Li²,

Duan³

et al. 2011

Afr. J. Pharm. Pharmacol.

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Intercellular gap junction (GJ) plays a pivotal role in the proliferation and transformation of vascular smooth muscle cells (VSMCs). This study was designed to test the hypothesis that expressions of the component proteins of gap junctions, connexins40 and 43 (Cx40 and Cx43), are up-regulated in arteries subjected to balloon injury and that this up-regulation can be suppressed by statin therapy. Transmission electron microscopy (TEM) revealed that there were abundant GJ between neointimal SMCs but fewer and smaller GJ after losartan and ramipril treatment. Reverse transcription-polymerase chain reaction and Western blot analysis showed the messenger ribonucleic acid (mRNA) and protein expressions of Cx40 and Cx43 were elevated after injury, and these elevations were suppressed by losartan and ramipril. Immunostaining showed the Cx40 and Cx43 expressions were consistently enhanced in the neointimal area after injury, which was decreased by losartan and ramipril treatment. Balloon injury causes up-regulation of Cx40 and Cx43 in neointimal SMCs. angiotensin-converting enzyme inhibitors (ACEIs) and AT 1 antagonist losartan can reduce the proliferation of SMCs, suggesting the rennin-angiotensin system (RAS) system plays an important role in the remodeling of GJ in the VSMCs under pathological conditions.

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“…[17] Finally, Ang 1-7 and Ang II would exert opposite effects on the connexins of gap intercellular junctions, which may be altered by both AT-1 and Ang II and protected by Ang 1-7. [49]…”

Section: The Protective Action Of Ang 1-7 On Lung and Cardiovascular ...mentioning

confidence: 99%

A Review on the Potential Therapeutic Properties of Angiotensin 1-7 in Most Systemic Human Diseases

Lissoni,

Porro,

Rovelli

et al. 2020

Clin Res Hematol

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COVID-19 disease has dramatically demonstrated the fundamental role of angiotensin-converting enzyme 2 and its active product angiotensin 1-7 (Ang 1-7) in the inhibitory control of cytokine-induced inflammatory response, whose importance was not taken into consideration in the clinical practices. On the contrary, several experimental and clinical studies have shown that Ang 1-7 in addition to its hypotensive and cardioprotective actions may also play anti-inflammatory, antitumor, antithrombotic, and antifibrotic effects, then a potential regenerative activity. Most systemic human diseases, including advanced cancer, autoimmunity, cardiovascular disease, neurodegenerative pathologies, metabolic syndrome, and aging itself would be characterized by a reduced Ang 1-7 production and activity. Unfortunately, despite its potential universal therapeutic properties and its lack of toxicity, at present, few clinical studies have been performed to evaluate the therapeutic efficacy of Ang 1-7 in the different human pathologies in an attempt to prolong the duration of life.

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Effects of Losartan on expression of connexins at the early stage of atherosclerosis in rabbits

Cited by 5 publications

References 16 publications

Establishment of an interleukin-1β-induced inflammation-activated endothelial cell-smooth muscle cell-mononuclear cell co-culture model and evaluation of the anti-inflammatory effects of tanshinone IIA on atherosclerosis

Establishment of an interleukin-1β-induced inflammation-activated endothelial cell-smooth muscle cell-mononuclear cell co-culture model and evaluation of the anti-inflammatory effects of tanshinone IIA on atherosclerosis

Effects of Losartan and Ramipril on the connexin expression in a rabbit balloon injury model

A Review on the Potential Therapeutic Properties of Angiotensin 1-7 in Most Systemic Human Diseases

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