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Connexins in cardiovascular and neurovascular health and disease : pharmacological implications

(2017) PHARMACOLOGICAL REVIEWS. 69(4). p.396-478
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Abstract
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.
Keywords
GAP-JUNCTION CHANNELS, PROTEIN-KINASE-C, SPINAL-CORD-INJURY, ANTIARRHYTHMIC PEPTIDE AAP10, ISCHEMIA-REPERFUSION INJURY, SMOOTH-MUSCLE-CELLS, MYOCARDIAL INFARCT SIZE, CENTRAL-NERVOUS-SYSTEM, SPONTANEOUSLY HYPERTENSIVE-RATS, CHRONIC ATRIAL-FIBRILLATION

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MLA
Leybaert, Luc et al. “Connexins in Cardiovascular and Neurovascular Health and Disease : Pharmacological Implications.” PHARMACOLOGICAL REVIEWS 69.4 (2017): 396–478. Print.
APA
Leybaert, L., Lampe, P. D., Dhein, S., Kwak, B. R., Ferdinandy, P., Beyer, E. C., Laird, D. W., et al. (2017). Connexins in cardiovascular and neurovascular health and disease : pharmacological implications. PHARMACOLOGICAL REVIEWS, 69(4), 396–478.
Chicago author-date
Leybaert, Luc, Paul D Lampe, Stefan Dhein, Brenda R Kwak, Peter Ferdinandy, Eric C Beyer, Dale W Laird, Christian C Naus, Colin R Green, and Rainer Schulz. 2017. “Connexins in Cardiovascular and Neurovascular Health and Disease : Pharmacological Implications.” Pharmacological Reviews 69 (4): 396–478.
Chicago author-date (all authors)
Leybaert, Luc, Paul D Lampe, Stefan Dhein, Brenda R Kwak, Peter Ferdinandy, Eric C Beyer, Dale W Laird, Christian C Naus, Colin R Green, and Rainer Schulz. 2017. “Connexins in Cardiovascular and Neurovascular Health and Disease : Pharmacological Implications.” Pharmacological Reviews 69 (4): 396–478.
Vancouver
1.
Leybaert L, Lampe PD, Dhein S, Kwak BR, Ferdinandy P, Beyer EC, et al. Connexins in cardiovascular and neurovascular health and disease : pharmacological implications. PHARMACOLOGICAL REVIEWS. 2017;69(4):396–478.
IEEE
[1]
L. Leybaert et al., “Connexins in cardiovascular and neurovascular health and disease : pharmacological implications,” PHARMACOLOGICAL REVIEWS, vol. 69, no. 4, pp. 396–478, 2017.
@article{8540479,
  abstract     = {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.},
  author       = {Leybaert, Luc and Lampe, Paul D and Dhein, Stefan and Kwak, Brenda R and Ferdinandy, Peter and Beyer, Eric C and Laird, Dale W and Naus, Christian C and Green, Colin R and Schulz, Rainer},
  issn         = {0031-6997},
  journal      = {PHARMACOLOGICAL REVIEWS},
  keywords     = {GAP-JUNCTION CHANNELS,PROTEIN-KINASE-C,SPINAL-CORD-INJURY,ANTIARRHYTHMIC PEPTIDE AAP10,ISCHEMIA-REPERFUSION INJURY,SMOOTH-MUSCLE-CELLS,MYOCARDIAL INFARCT SIZE,CENTRAL-NERVOUS-SYSTEM,SPONTANEOUSLY HYPERTENSIVE-RATS,CHRONIC ATRIAL-FIBRILLATION},
  language     = {eng},
  number       = {4},
  pages        = {396--478},
  title        = {Connexins in cardiovascular and neurovascular health and disease : pharmacological implications},
  url          = {http://dx.doi.org/10.1124/pr.115.012062},
  volume       = {69},
  year         = {2017},
}

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