Mechanisms regulating cerebral hypoperfusion in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy

Xi Yan; Junkui Shang; Runrun Wang; Fengyu Wang; Jiewen Zhang

doi:10.7555/JBR.36.20220208

Volume 36 Issue 5

Sep. 2022

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Xi Yan, Junkui Shang, Runrun Wang, Fengyu Wang, Jiewen Zhang. Mechanisms regulating cerebral hypoperfusion in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy[J]. The Journal of Biomedical Research, 2022, 36(5): 353-357. doi: 10.7555/JBR.36.20220208

Citation:

Xi Yan, Junkui Shang, Runrun Wang, Fengyu Wang, Jiewen Zhang. Mechanisms regulating cerebral hypoperfusion in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy[J]. The Journal of Biomedical Research, 2022, 36(5): 353-357. doi: 10.7555/JBR.36.20220208

Citation:

Xi Yan, Junkui Shang, Runrun Wang, Fengyu Wang, Jiewen Zhang. Mechanisms regulating cerebral hypoperfusion in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy[J]. The Journal of Biomedical Research, 2022, 36(5): 353-357. doi: 10.7555/JBR.36.20220208

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Mechanisms regulating cerebral hypoperfusion in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy

doi: 10.7555/JBR.36.20220208

Department of Neurology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Henan University People's Hospital, Zhengzhou, Henan 450003, China

Funds: This work was supported by National Natural Science Foundation of China (Grants No. 81873727 and 82171196).

More Information

Corresponding author: Jiewen Zhang, Department of Neurology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Henan University People's Hospital, No. 7 Weiwu Road, Zhengzhou, Henan 450003, China. Tel: +86-371-65580782, E-mail: zhangjiewen9900@126.com
Received: 2022-02-21
Revised: 2022-06-15
Accepted: 2022-07-07

Published: 2022-08-28

Issue Date: 2022-09-28

Abstract

Abstract

Cerebral small vessel disease (CSVD) is a leading cause of stroke and dementia. As the most common type of inherited CSVD, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is characterized by the NOTCH3 gene mutation which leads to Notch3 ectodomain deposition and extracellular matrix aggregation around the small vessels. It further causes smooth muscle cell degeneration and small vessel arteriopathy in the central nervous system. Compromised cerebral blood flow occurs in the early stage of CADASIL and is associated with white matter hyperintensity, the typical neuroimaging pathology of CADASIL. This suggests that cerebral hypoperfusion may play an important role in the pathogenesis of CADASIL. However, the mechanistic linkage between NOTCH3 mutation and cerebral hypoperfusion remains unknown. Therefore, in this mini-review, it examines the cellular and molecular mechanisms contributing to cerebral hypoperfusion in CADASIL.
- cerebral hypoperfusion,
- CADASIL,
- Notch3,
- mural cell,
- astrocyte

CLC number: R743, Document code: A
The authors reported no conflict of interests.

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References(27)

References

[1]	Di Donato I, Bianchi S, De Stefano N, et al. Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) as a model of small vessel disease: update on clinical, diagnostic, and management aspects[J]. BMC Med, 2017, 15(1): 41. doi: 10.1186/s12916-017-0778-8
[2]	Schoemaker D, Quiroz YT, Torrico-Teave H, et al. Clinical and research applications of magnetic resonance imaging in the study of CADASIL[J]. Neurosci Lett, 2019, 698: 173–179. doi: 10.1016/j.neulet.2019.01.014
[3]	Huneau C, Houot M, Joutel A, et al. Altered dynamics of neurovascular coupling in CADASIL[J]. Ann Clin Transl Neurol, 2018, 5(7): 788–802. doi: 10.1002/acn3.574
[4]	Joutel A, Monet-Leprêtre M, Gosele C, et al. Cerebrovascular dysfunction and microcirculation rarefaction precede white matter lesions in a mouse genetic model of cerebral ischemic small vessel disease[J]. J Clin Invest, 2010, 120(2): 433–445. doi: 10.1172/JCI39733
[5]	Mašek J, Andersson ER. The developmental biology of genetic Notch disorders[J]. Development, 2017, 144(10): 1743–1763. doi: 10.1242/dev.148007
[6]	Liu H, Zhang W, Kennard S, et al. Notch3 is critical for proper angiogenesis and mural cell investment[J]. Circ Res, 2010, 107(7): 860–870. doi: 10.1161/CIRCRESAHA.110.218271
[7]	Monet-Leprêtre M, Haddad I, Baron-Menguy C, et al. Abnormal recruitment of extracellular matrix proteins by excess Notch3^ECD: a new pathomechanism in CADASIL[J]. Brain, 2013, 136(6): 1830–1845. doi: 10.1093/brain/awt092
[8]	Zellner A, Scharrer E, Arzberger T, et al. CADASIL brain vessels show a HTRA1 loss-of-function profile[J]. Acta Neuropathol, 2018, 136(1): 111–125. doi: 10.1007/s00401-018-1853-8
[9]	Fan D, Kassiri Z. Biology of tissue inhibitor of metalloproteinase 3 (TIMP3), and its therapeutic implications in cardiovascular pathology[J]. Front Physiol, 2020, 11: 661. doi: 10.3389/fphys.2020.00661
[10]	Capone C, Cognat E, Ghezali L, et al. Reducing Timp3 or vitronectin ameliorates disease manifestations in CADASIL mice[J]. Ann Neurol, 2016, 79(3): 387–403. doi: 10.1002/ana.24573
[11]	Capone C, Dabertrand F, Baron-Menguy C, et al. Mechanistic insights into a TIMP3-sensitive pathway constitutively engaged in the regulation of cerebral hemodynamics[J]. Elife, 2016, 5: e17536. doi: 10.7554/eLife.17536
[12]	Hanemaaijer ES, Panahi M, Swaddiwudhipong N, et al. Autophagy-lysosomal defect in human CADASIL vascular smooth muscle cells[J]. Eur J Cell Biol, 2018, 97(8): 557–567. doi: 10.1016/j.ejcb.2018.10.001
[13]	Neves KB, Morris HE, Alves-Lopes R, et al. Peripheral arteriopathy caused by Notch3 gain-of-function mutation involves ER and oxidative stress and blunting of NO/sGC/cGMP pathway[J]. Clin Sci (Lond), 2021, 135(6): 753–773. doi: 10.1042/CS20201412
[14]	Henshall TL, Keller A, He L, et al. Notch3 is necessary for blood vessel integrity in the central nervous system[J]. Arterioscler Thromb Vasc Biol, 2015, 35(2): 409–420. doi: 10.1161/ATVBAHA.114.304849
[15]	Machuca-Parra AI, Bigger-Allen AA, Sanchez AV, et al. Therapeutic antibody targeting of Notch3 signaling prevents mural cell loss in CADASIL[J]. J Exp Med, 2017, 214(8): 2271–2282. doi: 10.1084/jem.20161715
[16]	Monet-Leprêtre M, Bardot B, Lemaire B, et al. Distinct phenotypic and functional features of CADASIL mutations in the Notch3 ligand binding domain[J]. Brain, 2009, 132(6): 1601–1612. doi: 10.1093/brain/awp049
[17]	Monet M, Domenga V, Lemaire B, et al. The archetypal R90C CADASIL-NOTCH3 mutation retains NOTCH3 function in vivo[J]. Hum Mol Genet, 2007, 16(8): 982–992. doi: 10.1093/hmg/ddm042
[18]	Baron-Menguy C, Domenga-Denier V, Ghezali L, et al. Increased Notch3 activity mediates pathological changes in structure of cerebral arteries[J]. Hypertension, 2017, 69(1): 60–70. doi: 10.1161/HYPERTENSIONAHA.116.08015
[19]	Kisler K, Nelson AR, Montagne A, et al. Cerebral blood flow regulation and neurovascular dysfunction in Alzheimer disease[J]. Nat Rev Neurosci, 2017, 18(7): 419–434. doi: 10.1038/nrn.2017.48
[20]	Brennan-Krohn T, Salloway S, Correia S, et al. Glial vascular degeneration in CADASIL[J]. J Alzheimers Dis, 2010, 21(4): 1393–1402. doi: 10.3233/JAD-2010-100036
[21]	Hase Y, Chen A, Bates LL, et al. Severe white matter astrocytopathy in CADASIL[J]. Brain Pathol, 2018, 28(6): 832–843. doi: 10.1111/bpa.12621
[22]	Mulligan SJ, MacVicar BA. Calcium transients in astrocyte endfeet cause cerebrovascular constrictions[J]. Nature, 2004, 431(7005): 195–199. doi: 10.1038/nature02827
[23]	Takano T, Tian G, Peng W, et al. Astrocyte-mediated control of cerebral blood flow[J]. Nat Neurosci, 2006, 9(2): 260–267. doi: 10.1038/nn1623
[24]	Jessen NA, Munk AS, Lundgaard I, et al. The glymphatic system: a beginner's guide[J]. Neurochem Res, 2015, 40(12): 2583–2599. doi: 10.1007/s11064-015-1581-6
[25]	Benveniste H, Nedergaard M. Cerebral small vessel disease: a glymphopathy?[J]. Curr Opin Neurobiol, 2022, 72: 15–21. doi: 10.1016/j.conb.2021.07.006
[26]	Koundal S, Elkin R, Nadeem S, et al. Optimal mass transport with lagrangian workflow reveals advective and diffusion driven solute transport in the glymphatic system[J]. Sci Rep, 2020, 10(1): 1990. doi: 10.1038/s41598-020-59045-9
[27]	Jiang Q, Zhang L, Ding G, et al. Impairment of the glymphatic system after diabetes[J]. J Cereb Blood Flow Metab, 2017, 37(4): 1326–1337. doi: 10.1177/0271678X16654702