CmPn/CmP Signaling Networks in the Maintenance of the Blood Vessel Barrier
Abstract
:1. Introduction
2. Key Factors Influencing Blood Vessel Permeability
2.1. EC Junctions
2.2. Inflammation and BBB Integrity
2.3. Angiogenic Factors and BBB Integrity
3. Angiogenic Impacts of Steroids on Maintenance of Vasculature
3.1. Steroids Can Influence the BBB Integrity
3.2. Steroids Might Play Major Roles for Compromised BBB
3.3. Steroids as Potential Therapeutics
4. Impacts of Sex Steroids on Maintenance of Vasculature
4.1. Neovascularization
4.2. Downstream Angiogenic Factors of PRG Signaling
5. Angiogenic Impacts of PRG on the Neurovascular Unit (NVU)
5.1. Neuroprotective Impact of PRGs on the NVU
5.2. Neuroprotective Effects of PRG and Its Derivatives on the BBB against Thrombin and Matrix Metalloproteinase (MMP)
5.3. Neuroprotective Effects of PRG on BBB against Inflammatory Pathway
5.4. Actions of PRG and Its Derivatives as Neurosteroids
6. Impacts of CmPn/CmP Networks on the BBB
6.1. The Impact of PRG-Mediated Signaling on Endothelial Cell (EC) Function in the Vasculature
6.2. CmPn/CmP Signaling Ntworks Maintain the BBB Integrity
7. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
5α-DHP | 5α-dihydroprogestrone |
AJs | adherens junctions |
ANG | angiopoietin |
AP | 3,5-tetrahydroxyprogesterone |
BBB | blood–brain barrier |
BDNF | brain-derived neurotrophic factor |
bFGF | basic fibroblast growth factor |
CCM | cerebral cavernous malformations |
CmP | CSC-mPRs-PRG |
CmPn | CSC-mPRs-PRG-nPRs |
CNS | central nervous system |
CSC | CCM signaling complex |
CSF | cerebrospinal fluid |
EC | endothelial cells |
PCs | pericytes |
BMs | basement membranes |
AE | astrocyte endfeet |
eNOS | endothelial nitric oxide synthase |
EST | estrogen |
fCCM | familial CCM |
GC | glucocorticoid |
GRs | glucocorticoid receptors |
HIF1a | Hypoxia-inducible factor 1a |
HRT | hormone replacement therapy |
HUVEC | human umbilical vein endothelial cells |
ICAM-1 | intercellular cell adhesion molecule 1 |
JAMs | junction adhesion molecules |
KO | knockout |
LPS | lipopolysaccharide |
MAPKs | mitogen-activated protein kinases |
MEFs | mouse embryonic fibroblasts |
MIF | mifepristone |
MMPs | matrix metalloproteinases |
mPRs | membrane PRG receptors |
MR | mineralocorticoid receptor |
MRI | magnetic resonance imaging |
NF-κB | nuclear factor kappa B |
NFAT | nuclear factor of activated T cells |
NO | nitric oxide |
NOS | nitric oxide synthase |
NVU | neurovascular unit |
nPR–s | nuclear PRG receptors |
PD-ECGF | platelet-derived EC growth factor |
PI3Ks | phosphoinositide 3-kinases |
PRG | progesterone |
PGRMC1,2 | progesterone receptor membrane component 1,2 |
siRNA | short interfering RNA |
Th | T helper |
TJs | tight junctions |
TBI | post-traumatic brain injury |
VCAM-1 | vascular cell adhesion molecule 1 |
VEGF | vascular endothelial growth factor |
WT | wildtype |
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Main Point | Key Findings | Genes Involved | Key References |
---|---|---|---|
Key factors influencing on the blood vessel permeability | The blood brain barrier (BBB, the blood vessel barrier) in the brain, is a dynamic and complex interface that tightly controls the molecular exchanges between the blood and central nervous system (CNS) the integrity of both BVB and BBB are determined by EC junctions that are made up of mainly adherens junctions (AJs) and tight junctions (TJs), which can be influenced by steroids. | JAMs, claudins, occludins, VE-cadherin, N-cadherin, VCAM-1, ICAM-1, | [15,16,27,28,73,75] |
Angiogenic impacts of steroids on maintenance of vasculature | Steroids might play major roles on maintainence of BBB integrity, through their regulation of EC junction components, dysregulation of steroid-mediasted signaling pathway can lead to compromised BBB, therefore, steroids can be potential therapeutic targets. | MRs, GRs, GRα, GRβ, ERs, nPRs, mPRs, eNOS | [78,81,83,99] |
Impacts of sex steroids on maintenance of vasculature | Sex steroids might play major roles on neovascularization, angiogenic signaling, and maintainence of BBB integrity, therefore, steroids can be potential therapeutic targets. | bFGF, PD-ECGF, HIF1a, Ang, NOS, eNOS, PI3Ks, Akt, MAPKs | [150,151,152,155] |
Angiogenic impacts of progesterone (PRG) on the Neurovascular Unit (NVU) | PRGs have neuroprotective impact on the Neurovascular Unit (NVU) | BDNF, PGRMC1, Bcl-2, PAR-1, Claudin-5, MMP, NF-κB, IL-10, GABA-A receptor | [147,150,151,153] |
Impacts of CmPn/CmP signaling networks on the BBB | PRG and its derivatives-mediated signaling pathways have major impacts on EC performance in vasculature. PRG and its derivatives-mediated CmPn/CmP signaling networks maintain the BBB integrity | CCM (1–3) genes, mPRs, nPRs, | [8,46,124,125,198] |
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Gnanasekaran, R.; Aickareth, J.; Hawwar, M.; Sanchez, N.; Croft, J.; Zhang, J. CmPn/CmP Signaling Networks in the Maintenance of the Blood Vessel Barrier. J. Pers. Med. 2023, 13, 751. https://doi.org/10.3390/jpm13050751
Gnanasekaran R, Aickareth J, Hawwar M, Sanchez N, Croft J, Zhang J. CmPn/CmP Signaling Networks in the Maintenance of the Blood Vessel Barrier. Journal of Personalized Medicine. 2023; 13(5):751. https://doi.org/10.3390/jpm13050751
Chicago/Turabian StyleGnanasekaran, Revathi, Justin Aickareth, Majd Hawwar, Nickolas Sanchez, Jacob Croft, and Jun Zhang. 2023. "CmPn/CmP Signaling Networks in the Maintenance of the Blood Vessel Barrier" Journal of Personalized Medicine 13, no. 5: 751. https://doi.org/10.3390/jpm13050751