Impact of the Renin–Angiotensin System on the Endothelium in Vascular Dementia: Unresolved Issues and Future Perspectives
Abstract
:1. Introduction
2. Role of the Renin–Angiotensin System
3. Endothelium
3.1. Angiotensin and AT1R
3.2. ACE2
3.3. Ang(1–7) and the Mas Receptor
3.4. Other Novel RAS Components: AT2 and AT4 Receptors
3.5. Role of Pericytes
4. Conclusions and Future Directions
Funding
Conflicts of Interest
References
- O’Brien, T.J.; Thomas, A. Vascular dementia. Lancet 2015, 386, 1698–1706. [Google Scholar] [CrossRef]
- van der Flier, W.M.; Scheltens, P. Epidemiology and risk factors of dementia. J. Neurol. Neurosurg. Psychiatry 2005, 76, v2–v7. [Google Scholar] [CrossRef] [PubMed]
- Yu, X.; Ji, C.; Shao, A. Neurovascular Unit Dysfunction and Neurodegenerative Disorders. Front. Neurosci. 2020, 14, 334. [Google Scholar] [CrossRef] [PubMed]
- Tarantini, S.; Tran, C.H.T.; Gordon, G.R.; Ungvari, Z.; Csiszar, A. Impaired neurovascular coupling in aging and Alzheimer’s disease: Contribution of astrocyte dysfunction and endothelial impairment to cognitive decline. Exp. Gerontol. 2017, 94, 52–58. [Google Scholar] [CrossRef] [PubMed]
- Csiszar, A.; Tarantini, S.; Fülöp, G.A.; Kiss, T.; Valcarcel-Ares, M.N.; Galvan, V.; Ungvari, Z.; Yabluchanskiy, A. Hypertension impairs neurovascular coupling and promotes microvascular injury: Role in exacerbation of Alzheimer’s disease. Geroscience 2017, 39, 359–372. [Google Scholar] [CrossRef]
- Pires, P.W.; Ramos, C.M.D.; Matin, N.; Dorrance, A.M. The effects of hypertension on the cerebral circulation. Am. J. Physiol.-Heart Circ. Physiol. 2013, 304, H1598–H1614. [Google Scholar] [CrossRef]
- Fulop, G.A.; Ramirez-Perez, F.I.; Kiss, T.; Tarantini, S.; Ares, M.N.V.; Toth, P.; Yabluchanskiy, A.; Conley, S.M.; Ballabh, P.; Martinez-Lemus, L.A.; et al. IGF-1 Deficiency Promotes Pathological Remodeling of Cerebral Arteries: A Potential Mechanism Contributing to the Pathogenesis of Intracerebral Hemorrhages in Aging. J. Gerontol. A Biol. Sci. Med. Sci. 2019, 74, 446–454. [Google Scholar] [CrossRef]
- Wiesmann, M.; Capone, C.; Zerbi, V.; Mellendijk, L.; Heerschap, A.; Claassen, J.A.H.R.; Kiliaan, A.J. Hypertension impairs cerebral blood flow in a mouse model for Alzheimer’s disease. Curr. Alzheimer Res. 2015, 12, 914–922. [Google Scholar] [CrossRef]
- Kim, D.; Yang, P.-S.; Jang, E.; Yu, H.T.; Kim, T.-H.; Uhm, J.-S.; Kim, J.-Y.; Sung, J.-H.; Pak, H.-N.; Lee, M.-H. Blood Pressure Control and Dementia Risk in Midlife Patients with Atrial Fibrillation. Hypertension 2020, 75, 1296–1304. [Google Scholar] [CrossRef]
- Cifuentes, D.; Poittevin, M.; Dere, E.; Broquères-You, D.; Bonnin, P.; Benessiano, J.; Pocard, M.; Mariani, J.; Kubis, N.; Merkulova-Rainon, T. Hypertension accelerates the progression of Alzheimer-like pathology in a mouse model of the disease. Hypertension 2015, 65, 218–224. [Google Scholar] [CrossRef]
- Abrahamson, E.E.; Ikonomovic, M.D. Brain injury-induced dysfunction of the blood brain barrier as a risk for dementia. Exp. Neurol. 2020, 328, 113257. [Google Scholar] [CrossRef]
- Kaplan, A.; Yabluchanskiy, A.; Ghali, R.; Altara, R.; Booz, G.W.; Zouein, F.A. Cerebral blood flow alteration following acute myocardial infarction in mice. Biosci. Rep. 2018, 38. [Google Scholar] [CrossRef] [PubMed]
- Shekhar, S.; Cunningham, M.W.; Pabbidi, M.R.; Wang, S.; Booz, G.W.; Fan, F. Targeting vascular inflammation in ischemic stroke: Recent developments on novel immunomodulatory approaches. Eur. J. Pharmacol. 2018, 833, 531–544. [Google Scholar] [CrossRef] [PubMed]
- Karnik, S.S.; Unal, H.; Kemp, J.R.; Tirupula, K.C.; Eguchi, S.; Vanderheyden, P.M.; Thomas, W.G. Angiotensin receptors: Interpreters of pathophysiological angiotensinergic stimulis. Pharmacol. Rev. 2015, 67, 754–819. [Google Scholar] [CrossRef] [PubMed]
- Forrester, S.J.; Booz, G.W.; Sigmund, C.D.; Coffman, T.M.; Kawai, T.; Rizzo, V.; Scalia, R.; Eguchi, S. Angiotensin II signal transduction: An update on mechanisms of physiology and pathophysiology. Physiol. Rev. 2018, 98, 1627–1738. [Google Scholar] [CrossRef] [PubMed]
- Wackenfors, A.; Vikman, P.; Nilsson, E.; Edvinsson, L.; Malmsjo, M. Angiotensin II-induced vasodilatation in cerebral arteries is mediated by endothelium-derived hyperpolarising factor. Eur. J. Pharmacol. 2006, 531, 259–263. [Google Scholar] [CrossRef] [PubMed]
- Haberl, R.L.; Anneser, F.; Villringer, A.; Einhaupl, K.M. Angiotensin II induces endothelium-dependent vasodilation of rat cerebral arterioles. Am. J. Physiol. 1990, 258, H1840–H1846. [Google Scholar] [CrossRef]
- Walker, A.E.; Kronquist, E.K.; Chinen, K.T.; Reihl, K.D.; Li, D.Y.; Lesniewski, L.A.; Donato, A.J. Cerebral and skeletal muscle feed artery vasoconstrictor responses in a mouse model with greater large elastic artery stiffness. Exp. Physiol. 2019, 104, 434–442. [Google Scholar] [CrossRef]
- Wang, F.; Cao, Y.; Ma, L.; Pei, H.; Rausch, W.D.; Li, H. Dysfunction of cerebrovascular endothelial cells: Prelude to vascular dementia. Front. Aging Neurosci. 2018, 10, 376. [Google Scholar] [CrossRef]
- Nation, D.A.; Sweeney, M.D.; Montagne, A.; Sagare, A.P.; D’Orazio, L.M.; Pachicano, M.; Sepehrband, F.; Nelson, A.R.; Buennagel, D.P.; Harrington, M.G. Blood–brain barrier breakdown is an early biomarker of human cognitive dysfunction. Nat. Med. 2019, 25, 270–276. [Google Scholar] [CrossRef]
- Montagne, A.; Barnes, S.R.; Sweeney, M.D.; Halliday, M.R.; Sagare, A.P.; Zhao, Z.; Toga, A.W.; Jacobs, R.E.; Liu, C.Y.; Amezcua, L. Blood-brain barrier breakdown in the aging human hippocampus. Neuron 2015, 85, 296–302. [Google Scholar] [CrossRef] [PubMed]
- Di Marco, L.Y.; Venneri, A.; Farkas, E.; Evans, P.C.; Marzo, A.; Frangi, A.F. Vascular dysfunction in the pathogenesis of Alzheimer’s disease—A review of endothelium-mediated mechanisms and ensuing vicious circles. Neurobiol. Dis. 2015, 82, 593–606. [Google Scholar] [CrossRef]
- Adamski, M.G.; Sternak, M.; Mohaissen, T.; Kaczor, D.; Wierońska, J.M.; Malinowska, M.; Czaban, I.; Byk, K.; Lyngsø, K.S.; Przyborowski, K. Vascular cognitive impairment linked to brain endothelium inflammation in early stages of heart failure in mice. J. Am. Heart Assoc. 2018, 7, e007694. [Google Scholar] [CrossRef]
- Yin, S.; Bai, W.; Li, P.; Jian, X.; Shan, T.; Tang, Z.; Jing, X.; Ping, S.; Li, Q.; Miao, Z. Berberine suppresses the ectopic expression of miR-133a in endothelial cells to improve vascular dementia in diabetic rats. Clin. Exp. Hypertens. 2019, 41, 708–716. [Google Scholar] [CrossRef]
- De Silva, T.M.; Faraci, F. Effects of angiotensin II on the cerebral circulation: Role of oxidative stress. Front. Physiol. 2013, 3, 484. [Google Scholar] [CrossRef] [PubMed]
- Yi, R.; Xiao-Ping, G.; Hui, L. Atorvastatin prevents angiotensin II-induced high permeability of human arterial endothelial cell monolayers via ROCK signaling pathway. Biochem. Biophys. Res. Commun. 2015, 459, 94–99. [Google Scholar] [CrossRef]
- Wosik, K.; Cayrol, R.; Dodelet-Devillers, A.; Berthelet, F.; Bernard, M.; Moumdjian, R.; Bouthillier, A.; Reudelhuber, T.L.; Prat, A. Angiotensin II controls occludin function and is required for blood brain barrier maintenance: Relevance to multiple sclerosis. J. Neurosci. 2007, 27, 9032–9042. [Google Scholar] [CrossRef] [PubMed]
- Islam, M.Z.; Kawaguchi, H.; Miura, N.; Miyoshi, N.; Yamazaki-Himeno, E.; Shiraishi, M.; Miyamoto, A.; Tanimoto, A. Hypertension alters the endothelial-dependent biphasic response of bradykinin in isolated Microminipig basilar artery. Microvasc. Res. 2017, 114, 52–57. [Google Scholar] [CrossRef] [PubMed]
- Chrissobolis, S.; Banfi, B.; Sobey, C.G.; Faraci, F.M. Role of Nox isoforms in angiotensin II-induced oxidative stress and endothelial dysfunction in brain. J. Appl. Physiol. 2012, 113, 184–191. [Google Scholar] [CrossRef]
- Girouard, H.; Park, L.; Anrather, J.; Zhou, P.; Iadecola, C. Angiotensin II attenuates endothelium-dependent responses in the cerebral microcirculation through nox-2–derived radicals. Arterioscler. Thromb. Vasc. Biol. 2006, 26, 826–832. [Google Scholar] [CrossRef]
- Masi, S.; Uliana, M.; Virdis, A. Angiotensin II and vascular damage in hypertension: Role of oxidative stress and sympathetic activation. Vasc. Pharmacol. 2019. [Google Scholar] [CrossRef] [PubMed]
- Fan, L.M.; Geng, L.; Cahill-Smith, S.; Liu, F.; Douglas, G.; Mckenzie, C.-A.; Smith, C.; Brooks, G.; Channon, K.M.; Li, J.-M. Nox2 contributes to age-related oxidative damage to neurons and the cerebral vasculature. J. Clin. Investig. 2019, 129, 3374–3386. [Google Scholar] [CrossRef] [PubMed]
- Xu, X.; Xu, H.; Liu, S.; Wang, H.; Hu, M.; Song, L. MAPK/AP-1 pathway activation mediates AT1R upregulation and vascular endothelial cells dysfunction under PM2. 5 exposure. Ecotoxicol. Environ. Saf. 2019, 170, 188–194. [Google Scholar] [CrossRef]
- Ma, M.-M.; Gao, M.; Guo, K.-M.; Wang, M.; Li, X.-Y.; Zeng, X.-L.; Sun, L.; Lv, X.-F.; Du, Y.-H.; Wang, G.-L. TMEM16A Contributes to Endothelial Dysfunction by Facilitating Nox2 NADPH Oxidase–Derived Reactive Oxygen Species Generation in Hypertension. Hypertension 2017, 69, 892–901. [Google Scholar] [CrossRef] [PubMed]
- Ungvari, Z.; Tarantini, S.; Nyul-Toth, A.; Kiss, T.; Yabluchanskiy, A.; Csipo, T.; Balasubramanian, P.; Lipecz, A.; Benyo, Z.; Csiszar, A. Nrf2 dysfunction and impaired cellular resilience to oxidative stressors in the aged vasculature: From increased cellular senescence to the pathogenesis of age-related vascular diseases. Geroscience 2019, 41, 727–738. [Google Scholar] [CrossRef] [PubMed]
- Guo, S.; Som, A.T.; Arai, K.; Lo, E.H. Effects of angiotensin-II on brain endothelial cell permeability via PPARalpha regulation of para-and trans-cellular pathways. Brain Res. 2019, 1722, 146353. [Google Scholar] [CrossRef]
- Hu, C.; Lu, K.-T.; Mukohda, M.; Davis, D.R.; Faraci, F.M.; Sigmund, C.D. Interference with PPARγ in endothelium accelerates angiotensin II-induced endothelial dysfunction. Physiol. Genom. 2016, 48, 124–134. [Google Scholar] [CrossRef]
- Yakubu, M.A.; Nsaif, R.H.; Oyekan, A.O. Peroxisome proliferator-activated receptor α activation-mediated regulation of endothelin-1 production via nitric oxide and protein kinase C signaling pathways in piglet cerebral microvascular endothelial cell culture. J. Pharmacol. Exp. Ther. 2007, 320, 774–781. [Google Scholar] [CrossRef]
- Chi, L.; Hu, X.; Zhang, W.; Bai, T.; Zhang, L.; Zeng, H.; Guo, R.; Zhang, Y.; Tian, H. Adipokine CTRP6 improves PPARγ activation to alleviate angiotensin II-induced hypertension and vascular endothelial dysfunction in spontaneously hypertensive rats. Biochem. Biophys. Res. Commun. 2017, 482, 727–734. [Google Scholar] [CrossRef]
- Beyer, A.M.; de Lange, W.J.; Halabi, C.M.; Modrick, M.L.; Keen, H.L.; Faraci, F.M.; Sigmund, C.D. Endothelium-specific interference with peroxisome proliferator activated receptor gamma causes cerebral vascular dysfunction in response to a high-fat diet. Circ. Res. 2008, 103, 654–661. [Google Scholar] [CrossRef]
- Nair, A.R.; Agbor, L.N.; Mukohda, M.; Liu, X.; Hu, C.; Wu, J.; Sigmund, C.D. Interference With Endothelial PPAR (Peroxisome Proliferator–Activated Receptor)-γ Causes Accelerated Cerebral Vascular Dysfunction in Response to Endogenous Renin-Angiotensin System Activation. Hypertension 2018, 72, 1227–1235. [Google Scholar] [CrossRef] [PubMed]
- Villapol, S.; Saavedra, J.M. Neuroprotective effects of angiotensin receptor blockers. Am. J. Hypertens. 2015, 28, 289–299. [Google Scholar] [CrossRef] [PubMed]
- Liu, H.; Mao, P.; Wang, J.; Wang, T.; Xie, C.-H. Azilsartan, an angiotensin II type 1 receptor blocker, attenuates tert-butyl hydroperoxide-induced endothelial cell injury through inhibition of mitochondrial dysfunction and anti-inflammatory activity. Neurochem. Int. 2016, 94, 48–56. [Google Scholar] [CrossRef] [PubMed]
- DuPont, J.J.; Jaffe, I.Z. The role of the mineralocorticoid receptor in the vasculature. J. Endocrinol. 2017, 234, T67. [Google Scholar] [CrossRef] [PubMed]
- Jaffe, I.Z.; Mendelsohn, M.E. Angiotensin II and aldosterone regulate gene transcription via functional mineralocortocoid receptors in human coronary artery smooth muscle cells. Circ. Res. 2005, 96, 643–650. [Google Scholar] [CrossRef]
- Keidar, S.; Gamliel-Lazarovich, A.; Kaplan, M.; Pavlotzky, E.; Hamoud, S.; Hayek, T.; Karry, R.; Abassi, Z. Mineralocorticoid receptor blocker increases angiotensin-converting enzyme 2 activity in congestive heart failure patients. Circ. Res. 2005, 97, 946–953. [Google Scholar] [CrossRef]
- Diaz-Otero, J.M.; Yen, T.-C.; Fisher, C.; Bota, D.; Jackson, W.F.; Dorrance, A.M. Mineralocorticoid receptor antagonism improves parenchymal arteriole dilation via a TRPV4-dependent mechanism and prevents cognitive dysfunction in hypertension. Am. J. Physiol.-Heart Circ. Physiol. 2018, 315, H1304–H1315. [Google Scholar] [CrossRef]
- McClain, J.L.; Dorrance, A.M. Temporary mineralocorticoid receptor antagonism during the development of hypertension improves cerebral artery dilation. Exp. Biol. Med. 2014, 239, 619–627. [Google Scholar] [CrossRef]
- Zhang, C.; Wang, J.; Ma, X.; Wang, W.; Zhao, B.; Chen, Y.; Chen, C.; Bihl, J.C. ACE2-EPC-EXs protect ageing ECs against hypoxia/reoxygenation-induced injury through the miR-18a/Nox2/ROS pathway. J. Cell. Mol. Med. 2018, 22, 1873–1882. [Google Scholar] [CrossRef]
- Wang, J.; Chen, S.; Bihl, J. Exosome-Mediated Transfer of ACE2 (Angiotensin-Converting Enzyme 2) from Endothelial Progenitor Cells Promotes Survival and Function of Endothelial Cell. Oxidative Med. Cell. Longev. 2020, 2020, 4213541. [Google Scholar] [CrossRef]
- Silva, R.A.P.; Chu, Y.; Miller, J.D.; Mitchell, I.J.; Penninger, J.M.; Faraci, F.M.; Heistad, D.D. Impact of ACE2 deficiency and oxidative stress on cerebrovascular function with aging. Stroke 2012, 43, 3358–3363. [Google Scholar] [CrossRef] [PubMed]
- Chen, J.; Xiao, X.; Chen, S.; Zhang, C.; Chen, J.; Yi, D.; Shenoy, V.; Raizada, M.K.; Zhao, B.; Chen, Y. Angiotensin-converting enzyme 2 priming enhances the function of endothelial progenitor cells and their therapeutic efficacy. Hypertension 2013, 61, 681–689. [Google Scholar] [CrossRef]
- Sriramula, S.; Xia, H.; Xu, P.; Lazartigues, E. Brain-targeted ACE2 overexpression attenuates neurogenic hypertension by inhibiting COX mediated inflammation. Hypertension 2015, 65, 577. [Google Scholar] [CrossRef] [PubMed]
- Chen, J.; Zhao, Y.; Chen, S.; Wang, J.; Xiao, X.; Ma, X.; Penchikala, M.; Xia, H.; Lazartigues, E.; Zhao, B. Neuronal over-expression of ACE2 protects brain from ischemia-induced damage. Neuropharmacology 2014, 79, 550–558. [Google Scholar] [CrossRef] [PubMed]
- Hay, M.; Polt, R.; Heien, M.L.; Vanderah, T.W.; Largent-Milnes, T.M.; Rodgers, K.; Falk, T.; Bartlett, M.J.; Doyle, K.P.; Konhilas, J.P. A Novel Angiotensin-(1-7) Glycosylated Mas Receptor Agonist for Treating Vascular Cognitive Impairment and Inflammation-Related Memory Dysfunction. J. Pharmacol. Exp. Ther. 2019, 369, 9–25. [Google Scholar] [CrossRef]
- Xiao, X.; Zhang, C.; Ma, X.; Miao, H.; Wang, J.; Liu, L.; Chen, S.; Zeng, R.; Chen, Y.; Bihl, J.C. Angiotensin-(1–7) counteracts angiotensin II-induced dysfunction in cerebral endothelial cells via modulating Nox2/ROS and PI3K/NO pathways. Exp. Cell Res. 2015, 336, 58–65. [Google Scholar] [CrossRef]
- Jiang, T.; Yu, J.T.; Zhu, X.C.; Zhang, Q.Q.; Tan, M.S.; Cao, L.; Wang, H.F.; Lu, J.; Gao, Q.; Zhang, Y.D. Angiotensin-(1–7) induces cerebral ischaemic tolerance by promoting brain angiogenesis in a Mas/eNOS-dependent pathway. Br. J. Pharmacol. 2014, 171, 4222–4232. [Google Scholar] [CrossRef]
- Levine, D.A.; Galecki, A.T.; Langa, K.M.; Unverzagt, F.W.; Kabeto, M.U.; Giordani, B.; Wadley, V.G. Trajectory of cognitive decline after incident stroke. JAMA 2015, 314, 41–51. [Google Scholar] [CrossRef]
- Wiesmann, M.; Kiliaan, A.J.; Claassen, J.A. Vascular aspects of cognitive impairment and dementia. J. Cereb. Blood Flow Metab. 2013, 33, 1696–1706. [Google Scholar] [CrossRef]
- Fukuoka, T.; Hayashi, T.; Hirayama, M.; Maruyama, H.; Mogi, M.; Horiuchi, M.; Takao, M.; Tanahashi, N. Platelet–endothelial cell interaction in brain microvessels of angiotensin II type-2 receptor knockout mice following transient bilateral common carotid artery occlusion. J. Thromb. Thrombolysis 2015, 40, 401–405. [Google Scholar] [CrossRef]
- Gallego-Delgado, J.; Basu-Roy, U.; Ty, M.; Alique, M.; Fernandez-Arias, C.; Movila, A.; Gomes, P.; Weinstock, A.; Xu, W.; Edagha, I. Angiotensin receptors and β-catenin regulate brain endothelial integrity in malaria. J. Clin. Investig. 2016, 126, 4016–4029. [Google Scholar] [CrossRef] [PubMed]
- Ahmed, H.A.; Ishrat, T.; Pillai, B.; Fouda, A.Y.; Sayed, M.A.; Eldahshan, W.; Waller, J.L.; Ergul, A.; Fagan, S.C. RAS modulation prevents progressive cognitive impairment after experimental stroke: A randomized, blinded preclinical trial. J. Neuroinflamm. 2018, 15, 1–16. [Google Scholar] [CrossRef]
- Eldahshan, W.; Ishrat, T.; Pillai, B.; Sayed, M.A.; Alwhaibi, A.; Fouda, A.Y.; Ergul, A.; Fagan, S.C. Angiotensin II type 2 receptor stimulation with compound 21 improves neurological function after stroke in female rats: A pilot study. Am. J. Physiol.-Heart Circ. Physiol. 2019, 316, H1192–H1201. [Google Scholar] [CrossRef] [PubMed]
- Mateos, L.; Perez-Alvarez, M.J.; Wandosell, F. Angiotensin II type-2 receptor stimulation induces neuronal VEGF synthesis after cerebral ischemia. Biochim. Biophys. Acta (BBA)-Mol. Basis Dis. 2016, 1862, 1297–1308. [Google Scholar] [CrossRef] [PubMed]
- Sun, R.; He, T.; Pan, Y.; Katusic, Z.S. Effects of senescence and angiotensin II on expression and processing of amyloid precursor protein in human cerebral microvascular endothelial cells. Aging (Albany NY) 2018, 10, 100. [Google Scholar] [CrossRef]
- Dao, V.T.-V.; Medini, S.; Bisha, M.; Balz, V.; Suvorava, T.; Bas, M.; Kojda, G. Nitric oxide up-regulates endothelial expression of angiotensin II type 2 receptors. Biochem. Pharmacol. 2016, 112, 24–36. [Google Scholar] [CrossRef]
- Hafko, R.; Villapol, S.; Nostramo, R.; Symes, A.; Sabban, E.L.; Inagami, T.; Saavedra, J.M. Commercially available angiotensin II At2 receptor antibodies are nonspecific. PLoS ONE 2013, 8, e69234. [Google Scholar] [CrossRef]
- Singh, K.D.; Karnik, S.S. Angiotensin receptors: Structure, function, signaling and clinical applications. J. Cell Signal. 2016, 1, 111. [Google Scholar] [CrossRef]
- Royea, J.; Martinot, P.; Hamel, E. Memory and cerebrovascular deficits recovered following angiotensin IV intervention in a mouse model of Alzheimer’s disease. Neurobiol. Dis. 2020, 134, 104644. [Google Scholar] [CrossRef]
- Hirunpattarasilp, C.; Attwell, D.; Freitas, F. The role of pericytes in brain disorders: From the periphery to the brain. J. Neurochem. 2019, 150, 648–665. [Google Scholar] [CrossRef]
- Kuroda, J.; Ago, T.; Nishimura, A.; Nakamura, K.; Matsuo, R.; Wakisaka, Y.; Kamouchi, M.; Kitazono, T. Nox4 is a major source of superoxide production in human brain pericytes. J. Vasc. Res. 2014, 51, 429–438. [Google Scholar] [CrossRef]
- García-Quintans, N.; Sánchez-Ramos, C.; Prieto, I.; Tierrez, A.; Arza, E.; Alfranca, A.; Redondo, J.M.; Monsalve, M. Oxidative stress induces loss of pericyte coverage and vascular instability in PGC-1α-deficient mice. Angiogenesis 2016, 19, 217–228. [Google Scholar] [CrossRef] [PubMed]
- Uemura, M.T.; Maki, T.; Ihara, M.; Lee, V.M.; Trojanowski, J.Q. Brain Microvascular Pericytes in Vascular Cognitive Impairment and Dementia. Front. Aging Neurosci. 2020, 12, 80. [Google Scholar] [CrossRef] [PubMed]
- Baradaran, A.; Nasri, H.; Rafieian-Kopaei, M. Oxidative stress and hypertension: Possibility of hypertension therapy with antioxidants. J. Res. Med. Sci. Off. J. Isfahan Univ. Med. Sci. 2014, 19, 358. [Google Scholar]
- Beltramo, E.; Berrone, E.; Giunti, S.; Gruden, G.; Perin, P.C.; Porta, M. Effects of mechanical stress and high glucose on pericyte proliferation, apoptosis and contractile phenotype. Exp. Eye Res. 2006, 83, 989–994. [Google Scholar] [CrossRef] [PubMed]
- Shimizu, F.; Sano, Y.; Tominaga, O.; Maeda, T.; Abe, M.A.; Kanda, T. Advanced glycation end-products disrupt the blood-brain barrier by stimulating the release of transforming growth factor-beta by pericytes and vascular endothelial growth factor and matrix metalloproteinase-2 by endothelial cells in vitro. Neurobiol. Aging 2013, 34, 1902–1912. [Google Scholar] [CrossRef]
- Kawamura, H.; Kobayashi, M.; Li, Q.; Yamanishi, S.; Katsumura, K.; Minami, M.; Wu, D.M.; Puro, D.G. Effects of angiotensin II on the pericyte-containing microvasculature of the rat retina. J. Physiol. 2004, 561, 671–683. [Google Scholar] [CrossRef]
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Noureddine, F.Y.; Altara, R.; Fan, F.; Yabluchanskiy, A.; Booz, G.W.; Zouein, F.A. Impact of the Renin–Angiotensin System on the Endothelium in Vascular Dementia: Unresolved Issues and Future Perspectives. Int. J. Mol. Sci. 2020, 21, 4268. https://doi.org/10.3390/ijms21124268
Noureddine FY, Altara R, Fan F, Yabluchanskiy A, Booz GW, Zouein FA. Impact of the Renin–Angiotensin System on the Endothelium in Vascular Dementia: Unresolved Issues and Future Perspectives. International Journal of Molecular Sciences. 2020; 21(12):4268. https://doi.org/10.3390/ijms21124268
Chicago/Turabian StyleNoureddine, Fatima Y., Raffaele Altara, Fan Fan, Andriy Yabluchanskiy, George W. Booz, and Fouad A. Zouein. 2020. "Impact of the Renin–Angiotensin System on the Endothelium in Vascular Dementia: Unresolved Issues and Future Perspectives" International Journal of Molecular Sciences 21, no. 12: 4268. https://doi.org/10.3390/ijms21124268