The distribution of matrix metalloproteinases and their tissue inhibitors in the brain vascular bed exposed to chronic tobacco smoke

Chertok V.M.; Zakharchuk N.V.; Nevzorova V.A.; Chertok A.G.

doi:https://doi.org/10.17116/jnevro20181186165

Chertok V.M.

Kafedra anatomii cheloveka Vladivostokskogo gosudarstvennogo meditsinskogo universiteta

Zakharchuk N.V.

Pacific State Medical University, Vladivostok, Russia

Nevzorova V.A.

Pacific State Medical University, Vladivostok, Russia

Chertok A.G.

Pacific State Medical University, Vladivostok, Russia

The distribution of matrix metalloproteinases and their tissue inhibitors in the brain vascular bed exposed to chronic tobacco smoke

Authors:

Chertok V.M., Zakharchuk N.V., Nevzorova V.A., Chertok A.G.

More about the authors

Journal: S.S. Korsakov Journal of Neurology and Psychiatry. 2018;118(6): 65‑71

DOI: 10.17116/jnevro20181186165

Read: 1090 times

Download PDF (RU)

Contact the author

Table of contents

To cite this article:

Chertok VM, Zakharchuk NV, Nevzorova VA, Chertok AG. The distribution of matrix metalloproteinases and their tissue inhibitors in the brain vascular bed exposed to chronic tobacco smoke. S.S. Korsakov Journal of Neurology and Psychiatry. 2018;118(6):65‑71. (In Russ.)
https://doi.org/10.17116/jnevro20181186165

Подписка 2026 Журнал неврологии и психиатрии им. С.С. Корсакова (S.S. Korsakov Journal of Neurology and Psychiatry)

Использование инфографики авторами научных работ

Close metadata

Recommended articles:

Assessment of the change over time of serum matrix metalloproteinases and vascular endothelial growth factor in the acute period of ischemic stroke. S.S. Korsakov Journal of Neurology and Psychiatry. 2025;(12-2):13-20

Assessment of biomarker levels in patients with STEMI, depending on the presence of cardiovascular events. Russian Journal of Preventive Medicine. 2025;(8):96-101

Abstract:

Objective. To study the distribution of MMP-2 and MMP-9 and their inhibitors (TIMP-2 and TIMP-1 respectively) in the brain vascular bed of rats exposed to chronic tobacco smoke. Material and methods. Localization and expression of MMP-2, MMP-9, TIMP-2 and TIMP-1 in the pial branches (I—V order vessels), intracerebral arteries and capillaries of rats exposed to tobacco smoke were studied for 36 weeks. The level of enzymatic activity was assessed by the relative quantity of enzymopositive arteries and amount of fragments per 1 mm2 and rate of immunohistochemical reaction. Specific capillary density per mm2 of brain tissue and optical density of the immunohistochemical product were calculated. Results. MMP-2 and TIMP-2 were found in all segments of the arterial course in control animals. In rats exposed to tobacco smoking, the expression of MMP-2 increased only in intracerebral arteries and capillaries while TIMP-2 level decreased. MMP-9 and TIMP-1 were noted only in single vessels, mainly small pial and intracerebral arteries, in intact animals. In rats exposed to tobacco smoke, MMP-9 expression significantly increased in all segments of the arterial course whereas the increase in TIMP-1 was observed mainly in large pial arteries. Conclusion. In physiological conditions, the dynamic balance between MMP-2 and TIMP-2 maintains basic tissue metabolism. Products of tobacco combustion are inductors of the inducible MMP-9 which promotes morphofunctional changes. The imbalance in MMP-9 — TIMP-1 system causes the degradation of extracellular matrix in different segments of the brain arterial course promoting the development of cerebral dysfunction.

Keywords:

matrix metalloproteinases

tissue inhibitor of metalloproteinases

pial arteries

cerebral capillaries

tobacco smoke

Authors:

Chertok V.M.

Kafedra anatomii cheloveka Vladivostokskogo gosudarstvennogo meditsinskogo universiteta

Zakharchuk N.V.

Pacific State Medical University, Vladivostok, Russia

Nevzorova V.A.

Pacific State Medical University, Vladivostok, Russia

Chertok A.G.

Pacific State Medical University, Vladivostok, Russia

Close metadata

References:

Poteryaeva ON. Matrix metalproteinases: structure, regulation, role in pathological states development (literature review). Meditsina i obrazovanie v Sibiri. 2010;5:7-17. (In Russ.)
Falzone L, Salemi R, Travali S, Scalisi A, McCubrey J, Candido S, Libra M. MMP-9 overexpression is associated with intragenic hypermethylation of MMP9 gene in melanoma. Aging. 2016;8(5):933-944. https://doi.org/10.18632/aging.100951
Johnson C, Galis ZS. Matrix metalloproteinase-2 and -9 differentially regulate smooth muscle cell migration and cell-mediated collagen organization. Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24(1):54-60. https://doi.org/10.1161/01.atv.0000100402.69997.c3
Gonzalez-Avila G, Delgado J, Mendoza-Posada DA, Sommer B, Ramos C, Aquino-Galvez A, Camacho C. Differences in plasma MMPs and TIMPs protein expression and chemotherapy response in patients with tobacco- or wood-smoke-induced lung cancer. Respiration. 2013;85(4):281-288. https://doi.org/10.1159/000336559
Grandas OH, Mountain DH, Kirkpatrick SS, Rudrapatna VS, Cassada DC, Stevens SL, Freeman MB, Goldman MH. Regulation of vascular smooth muscle cell expression and function of matrix metalloproteinases is mediated by estrogen and progesterone exposure. J Vasc Surg. 2009;49(1):185-191. https://doi.org/10.1016/j.jvs.2008.07.080
Ramachandran RK, Sorensen MD, Aaberg-Jessen C, Hermansen SK, Kristensen BW. Expression and prognostic impact of matrix metalloproteinase-2 (MMP-2) in astrocytomas. PLoS One. 2017;12(2):0172234. https://doi.org/10.1371/journal.pone.0172234
Chertok VM, Chertok AG. Zakharchuk NV, Nevzorova VA. Special patterns of matrix metalloproteinase-2 and its tissue inhibitor distribution in cellular capillaries of rat brain in case of experimental hypertension. Byulleten’ eksperimental’noi biologii i meditsiny. 2017;164(9):385-389. (In Russ.)
Candelario-Jalil E, Yang Y, Rosenberg GA. Diverse roles of matrix metalloproteinases and tissue inhibitors of metalloproteinases in neuroinflammation and cerebral ischemia. Neuroscience. 2009;158(3):983-994. https://doi.org/10.1016/j.neuroscience.2008.06.025
Cunningham LA, Wetzel M, Rosenberg GA. Multiple roles for MMPs and TIMPs in cerebral ischemia. Glia. 2005;50(4):329-339. https://doi.org/10.1002/glia.20169
Zheng H, Liu Y, Huang T, Fang Z, Li G, He S. Development and characterization of a rat model of chronic obstructive pulmonary disease (COPD) induced by sidestream cigarette smoke. Toxicology Letters. 2009;189(3):225-234. https://doi.org/10.1016/j.toxlet.2009.06.850
Zakharchuk NV, Chertok VM, Nevzorova VA, Gonchar EYu. Effects of chronic tobacco smoking on the distribution of tachykinin receptors in rat pial arteries. Byulleten’ eksperimental’noi biologii i meditsiny. 2017;163(3):313-316. (In Russ.) https://doi.org/10.1007/s10517-017-3792-0
Chertok VM, Kotsyuba AE. Endothelial (intimal) mechanism of cerebral hemodynamics regulation: changing views. Tikhookeanskii meditsinskii zhurnal. 2012;2:17-26. (In Russ.)
Chertok VM, Chertok AG. Regulatory capacity of the brain capillaries. Tikhookeanskii meditsinskii zhurnal. 2016;64(2):72-81. (In Russ.) https://doi.org/10.17238/pmj1609-1175.2016.2.72-81
Lakhan ShE, Kirchgessner A, Tepper D, Leonard A. Matrix Metalloproteinases and Blood-Brain Barrier Disruption in Acute Ischemic Stroke. Frontiers in Neurology. 2013;4:32-56. https://doi.org/10.3389/fneur.2013.00032
Rempe RG, Hartz AM, Bauer B. Matrix metalloproteinases in the brain and blood-brain barrier: Versatile breakers and makers. Journal of Cerebral Blood Flow & Metabolism. 2016;36(9):1481-1507. https://doi.org/10.1177/0271678x16655551
Florczak-Rzepka M, Grond-Ginsbach C, Montaner J, Steiner T. Matrix metalloproteinases in human spontaneous intracerebral hemorrhage: an update. Cerebrovasc Dis. 2012;34(4):249-262. https://doi.org/10.1159/000341686
Chertok VM. Mast cells of the outer coat of the arteries of the basis cerebri. Morfologiya. 1980;11(79):72-79. (In Russ.)
Zakharchuk NV, Nevzorova VA, Chertok VM, Sarafanova NS. Effects of chronic tabacco smoking on the cerebral blood flow. Zhurnal nevrologii i psikhiatrii im. S.S. Korsakova. 2017;117(2):124-129. (In Russ.) https://doi.org/10.17116/jnevro201711721124-129
Durazzo TC, Dieter J, Meyerhoff DJ, Nixon SJ. Chronic Cigarette Smoking: Implications for Neurocognition and Brain Neurobiology. International Journal of Environmental Research and Public Health. 2010;7(10):3760-3791. https://doi.org/10.3390/ijerph7103760
Mazzone P, Tierney W, Hossain M, Puvenna V, Janigro D, Cucullo L. Pathophysiological impact of cigarette smoke exposure on the cerebrovascular system with a focus on the blood-brain barrier: expanding the awareness of smoking toxicity in an underappreciated area. International Journal of Environmental Research and Public Health. 2010;7(12):4111-4126. https://doi.org/10.3390/ijerph7124111
Hossain M, Sathe T, Fazio V, Mazzone P, Weksler B, Janigro D, Rapp E, Cucullo L. Tobacco smoke: A critical etiological factor for vascular impairment at the bloodâ€”brain barrier. Brain Research. 2009;1287:192-205. https://doi.org/10.1016/j.brainres.2009.06.033