Knockdown of connexin 43 attenuates balloon injury-induced vascular restenosis through the inhibition of the proliferation and migration of vascular smooth muscle cells

Han, Xiao‐Jian; He, Dan; Xu, Liyao; Chen, Min; Wang, Yiqi; Feng, Jingyuan; Wei, Minjun; Hong, Tao; Jiang, Liping

doi:10.3892/ijmm.2015.2346

Cited by 8 publications

(4 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…connexin 43 (cx43), a member of the connexins family, is most abundantly expressed in the cardiac muscle (7). cx43 has been demonstrated to serve a role in a number of diseases, including oral squamous cell carcinoma, pancreatic cancer, prostate cancer, acute myeloid leukemia, myocardial edema, vascular restenosis and Parkinson's disease (8)(9)(10)(11)(12)(13)(14)(15)(16)(17). cx43 is primarily a fast, low-resistance pathway that regulates electrical conduction between cardiomyocytes, coordinates mechanical and electrical activities of cardiac muscle and controls the conduction velocity of impulses to ensure that myocardial electromechanical activities are synchronized (18).…”

Section: Introductionmentioning

confidence: 99%

Connexin 43 reduces susceptibility to sympathetic atrial fibrillation

et al. 2018

View full text Add to dashboard Cite

Atrial fibrillation (AF) is the most common arrhythmia reported in clinical practice. Connexin 43 (Cx43) is a member of the connexin protein family, which serves important roles in signal transduction in vivo. The aim of the present study was to investigate the role of Cx43 in the induction and maintenance of atrial fibrillation by using an animal model of sympathomimetic atrial fibrillation. Cx43 was successfully knocked down in the myocardium with gene‑specific small interfering (si)RNA via lentiviral infection. A total of 25 dogs were randomly and evenly divided into five groups: Normal (N), rapid atrial pacing (RAP), isoproterenol (ISO) + RAP, RAP + Cx43 siRNA and ISO + RAP + Cx43 siRNA. The mRNA and protein levels, as well as the distribution of Cx43 on the cell membrane, were gradually decreased in each group compared with the N group following treatment (P<0.05). The induction rate of the atrial effective refractory period was not significantly affected in the RAP and RAP + Cx43 siRNA groups, whereas it was significantly reduced in the ISO + RAP and ISO + RAP + Cx43 siRNA groups compared with the N group (P<0.05). The induction rate of AF was gradually increased in the RAP + Cx43 siRNA, ISO + RAP and ISO + RAP + Cx43 siRNA groups compared with the N group (P<0.05). The expression of nerve growth factor (NGF) and tyrosine hydroxylase (TH) was gradually increased in the ISO + RAP and ISO + RAP + Cx43 siRNA groups compared with their respective controls (RAP and RAP + Cx43 siRNA groups, respectively). However, no significant difference in the levels of NGF and TH was observed between the RAP, RAP + Cx43 siRNA, ISO + RAP and ISO + RAP + Cx43 siRNA groups. The mitochondrial morphology in each group was notably altered compared with the N group. The mitochondrial reactive oxygen species production and apoptotic index were gradually increased in each group compared with the N group (P<0.05). The results of the present study suggest that Cx43 reduces susceptibility to AF. Downregulation of Cx43 mediates the induction and maintenance of sympathetic AF.

show abstract

Section: Introductionmentioning

confidence: 99%

Connexin 43 reduces susceptibility to sympathetic atrial fibrillation

et al. 2018

View full text Add to dashboard Cite

show abstract

“…This suggests that Cx43 might be an attractive target for local delivery strategies aimed at reducing restenosis. Interestingly, effective knock-down of Cx43 was recently achieved with a lentiviral vector expressing Cx43targeting shRNA and also resulted in an attenuation of neointima formation after balloon injury in rats (Han et al, 2015). Surprisingly, smooth muscle-targeted knockout of Cx43 enhanced neointima formation in response to carotid wire or occlusion injury (Liao et al, 2007).…”

Section: Connexins In Restenosismentioning

confidence: 99%

Connexins in Cardiovascular and Neurovascular Health and Disease: Pharmacological Implications

Leybaert¹,

Lampe²,

Dhein³

et al. 2017

Pharmacol Rev

204

192

View full text Add to dashboard Cite

Connexins are ubiquitous channel forming proteins that assemble as plasma membrane hemichannels and as intercellular gap junction channels that directly connect cells. In the heart, gap junction channels electrically connect myocytes and specialized conductive tissues to coordinate the atrial and ventricular contraction/relaxation cycles and pump function. In blood vessels, these channels facilitate long-distance endothelial cell communication, synchronize smooth muscle cell contraction, and support endothelial-smooth muscle cell communication. In the central nervous system they form cellular syncytia and coordinate neural function. Gap junction channels are normally open and hemichannels are normally closed, but pathologic conditions may restrict gap junction communication and promote hemichannel opening, thereby disturbing a delicate cellular communication balance. Until recently, most connexin-targeting agents exhibited little specificity and several off-target effects. Recent work with peptide-based approaches has demonstrated improved specificity and opened avenues for a more rational approach toward independently modulating the function of gap junctions and hemichannels. We here review the role of connexins and their channels in cardiovascular and neurovascular health and disease, focusing on crucial regulatory aspects and identification of potential targets to modify their function. We conclude that peptide-based investigations have raised several new opportunities for interfering with connexins and their channels that may soon allow preservation of gap junction communication, inhibition of hemichannel opening, and mitigation of inflammatory signaling.

show abstract

“…Acute myocardial infarction (AMI) is a leading cause of clinical morbidity and mortality (1)(2)(3). Currently, various reperfusion therapies, including pharmacological interventions (e.g., thrombolytics) and/or invasive manipulations (e.g., angioplasty) constitute the most effective strategies for the treatment of AMI (4).…”

Section: Introductionmentioning

confidence: 99%

Radioprotective 105 kDa protein attenuates ischemia/reperfusion-induced myocardial apoptosis and autophagy by inhibiting the activation of the TLR4/NF-κB signaling pathway in rats

Guo

Jiang

Yang

et al. 2016

International Journal of Molecular Medicine

View full text Add to dashboard Cite

Toll-like receptor 4 (TLR4) serves as an important inducer of apoptotic and autophagic responses in myocardial ischemia/reperfusion (I/R) injury (MIRI). Radioprotective 105 kDa protein (RP105) is a specific inhibitor of TLR4. However, the molecular mechanisms by which RP105 represses myocardial apoptosis and autophagy through TLR4‑mediated signaling during I/R have not yet been fully elucidated. Therefore, in the present study, we aimed to examine whether adenovirus-mediated RP105 overexpression repressed myocardial apoptosis and autophagy by inhibiting the TLR4-driven mechanism in MIRI. Three days after the injection of virus or saline into the myocardium, Sprague-Dawley (SD) rats were subjected to 30 min of left anterior descending coronary artery occlusion and 6 h of reperfusion. Myocardial specimens were prepared for analysis. We performed immunohistochemichal and histopathological analysis, the measurement of cardiac biomarkers, TUNEL assay , RT-qPCR and western blot analysis. The results indicated that the overexpression of RP105 contributed to an amelioration of myocardial histological damage, decreased leakage of creatine kinase (CK) and lactate dehydrogenase (LDH), as well as a reduction in the number of TUNEL-positive cardiomyocytes. The levels of positively associated modulators of apoptosis and autophagy were also significantly downregulated by RP105, whereas Bcl-2, which plays an opposite role in inducing apoptosis and autophagy, was inversely upregulated. Furthermore, the overexpression of RP105 led to the repression of TLR4 activity and the phosphorylation of NF-κB/p65, as well as the reduced production of the cytokines interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α). Taken together, these data suggest that RP105 protects the myocardium against apoptosis and autophagy, and plays a cardioprotective role during I/R injury. This is most likely due to the inactivation of TLR4/NF-κB signaling pathway. Thus, RP105 may represent an innovative therapeutic target for attenuating MIRI.

show abstract

Knockdown of connexin 43 attenuates balloon injury-induced vascular restenosis through the inhibition of the proliferation and migration of vascular smooth muscle cells

Cited by 8 publications

References 35 publications

Connexin 43 reduces susceptibility to sympathetic atrial fibrillation

Connexin 43 reduces susceptibility to sympathetic atrial fibrillation

Connexins in Cardiovascular and Neurovascular Health and Disease: Pharmacological Implications

Radioprotective 105 kDa protein attenuates ischemia/reperfusion-induced myocardial apoptosis and autophagy by inhibiting the activation of the TLR4/NF-κB signaling pathway in rats

Contact Info

Product

Resources

About