Peritubular Capillary Rarefaction: An Underappreciated Regulator of CKD Progression
Abstract
:1. Background
2. Anatomy of PTC
3. Clinical Significance of PTC Rarefaction
4. Mechanisms of PTC Rarefaction
4.1. Established Major Mechanisms—Loss of Endothelial Survival Factors
4.2. PTC Endothelium Quickly Responds to CKD Development
4.3. PTC Endothelium Is a Unique Population with Low Proliferative Potential
4.4. EC Apoptosis Is a Pivotal Cause of PTC Dropout
4.5. Pericyte Detachment Worsens PTC Loss
5. Major Factors Affecting PTC Loss
5.1. VEGF-A
5.2. Angiopoietin/Tie
5.3. HIF
5.4. Sirtuin
5.5. Vasohibin
5.6. Pericyte-Endothelial Cell Interaction
5.7. Endothelial Progenitor Cells
5.8. Endothelial to Mesenchymal Transition (EndMT)
6. Assessment of PTC Loss or Its Surrogate Marker, Tissue Hypoxia
6.1. Histological Assessment
6.2. Micro-Computed Tomography (Micro-CT)
6.3. Renal Resistive Index
6.4. Endothelial Micro-Particles
6.5. BOLD-MRI
7. Therapy to Mitigate PTC Rarefaction
7.1. Anti-Hypertensive Drugs
7.2. Sodium Glucose Cotransporter Inhibitor for Diabetic Nephropathy
7.3. Tie2 Activator
7.4. Nicotinamide (NAM)
7.5. PHD Inhibitor
7.6. Nintedanib
8. Capillary Rarefaction in Other Organs
9. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
CKD | chronic kidney disease |
PTC | peritubular capillary |
ESRD | end-stage renal disease |
DVR | descending vasa recta |
AVR | ascending vasa recta |
EC | endothelial cell |
GFR | glomerular filtration ratio |
VEGF-A | vascular endothelial growth factor-A |
VEGFR2 | vascular endothelial growth factor receptor-2 |
BUN | blood urea nitrogen |
Angpt-1 | angiopoietin-1 |
TSP-1 | thrombospondin-1 |
TNF-α | tumor necrosis factor-α |
IL-1β | interleukin-1β |
UUO | unilateral ureteral obstruction |
IRI | ischemia reperfusion injury |
PI3K | phosphoinositide-3-kinase |
FOXO1 | forkhead box O-1 |
PTEN | phosphatase and tensin homolog |
HIF | hypoxia-inducible factor |
FoxD1 | forkhead box D-1 |
TGF-β | transforming growth factor-β |
EPO | erythropoietin |
PDGF-B | platelet-derived growth factor-B |
AKI | acute kidney injury |
VE-PTP | vascular endothelial-protein tyrosine phosphatase |
PHD | prolyl hydroxylase domain-containing protein |
NAD | nicotinamide adenine dinucleotide |
SIPS | stress-induced premature senescence |
MMP | matrix metalloproteinase |
VASH | vasohibin |
PDGFRβ | platelet-derived growth factor receptor-β |
EPC | endothelial progenitor cell |
EndMT | endothelial to mesenchymal transition |
RRI | renal resistive index |
EMP | endothelial microparticles |
PL-VAP | plasmalemmal-vesicle-associated protein |
BOLD-MRI | blood oxygen level-dependent-magnetic resonance imaging |
ACE | angiotensin-converting enzyme |
ARB | angiotensin II receptor blocker |
SPL | spironolactone |
ET-A | endothelin-A receptor |
SGLT2 | sodium glucose cotransporter 2 |
NMN | nicotinamide mononucleotide |
NAM | nicotinamide |
IPF | idiopathic pulmonary fibrosis |
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Kida, Y. Peritubular Capillary Rarefaction: An Underappreciated Regulator of CKD Progression. Int. J. Mol. Sci. 2020, 21, 8255. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21218255
Kida Y. Peritubular Capillary Rarefaction: An Underappreciated Regulator of CKD Progression. International Journal of Molecular Sciences. 2020; 21(21):8255. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21218255
Chicago/Turabian StyleKida, Yujiro. 2020. "Peritubular Capillary Rarefaction: An Underappreciated Regulator of CKD Progression" International Journal of Molecular Sciences 21, no. 21: 8255. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21218255