The Possible Roles of Brain Pericytes in Brain Ischemia and Stroke

Kamouchi, Masahiro; Ago, Tetsuro; Kuroda, Junya; Kitazono, Takanari

doi:10.1007/s10571-011-9747-5

Cited by 39 publications

(21 citation statements)

References 86 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Pericytes have been proposed to play a pivotal role during brain ischemia and in the post-stroke period through mechanisms such as contraction of pericytes [32] and angiogenesis [2,6]. Hypoxic stress has been shown to induce ROS production in the brain [33].…”

Section: Discussionmentioning

confidence: 99%

“…In the present study, Nox4 was also involved in the proliferation of human brain pericytes. Proliferation of pericytes is an essential event in angiogenesis, in which these cells are capable of guiding sprouting processes by migrating ahead of endothelial cells or maturing the newly formed capillaries [1,6,8]. Taken together, superoxide production through Nox4 in brain pericytes may be involved in angiogenesis in the brain by regulating the proliferation of cells.…”

Section: Discussionmentioning

confidence: 99%

“…The highest density of pericytes in the body is found in vessels of neural tissues, such as the brain and retina [1,4]. In cerebral vessels, pericytes are proposed to have important roles in the regulation of cerebral microcirculation and angiogenesis, maintenance of the blood-brain barrier, and immune response [5,6,7,8,9]. …”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Nox4 Is a Major Source of Superoxide Production in Human Brain Pericytes

Kuroda¹,

Ago²,

Nishimura³

et al. 2014

J Vasc Res

Self Cite

View full text Add to dashboard Cite

Background: Pericytes are multifunctional cells surrounding capillaries and postcapillary venules. In brain microvasculature, pericytes play a pivotal role under physiological and pathological conditions by producing reactive oxygen species (ROS). The aims of this study were to elucidate the source of ROS and its regulation in human brain pericytes. Methods: The expression of Nox enzymes in the cells was evaluated using RT-PCR and western blot. Superoxide production was determined by superoxide dismutase-inhibitable chemiluminescence. Silencing of Nox4 was performed using RNAi, and cell proliferation was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay. Results: Nox4 was predominant among the Nox family in human brain pericytes. Membrane fractions of cells produced superoxide in the presence of NAD(P)H. Superoxide production was almost abolished with diphenileneiodonium, a Nox inhibitor; however, inhibitors of other possible superoxide-producing enzymes had no effect on NAD(P)H-dependent superoxide production. Pericytes expressed angiotensin II (Ang II) receptors, and Ang II upregulated Nox4 expression. Hypoxic conditions also increased the Nox4 expression. Silencing of Nox4 significantly reduced ROS production and attenuated cell proliferation. Conclusion: Our study showed that Nox4 is a major superoxide-producing enzyme and that its expression is regulated by Ang II and hypoxic stress in human brain pericytes. In addition, Nox4 may promote cell growth.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Nox4 Is a Major Source of Superoxide Production in Human Brain Pericytes

Kuroda¹,

Ago²,

Nishimura³

et al. 2014

J Vasc Res

Self Cite

View full text Add to dashboard Cite

show abstract

“…In capillaries and venules, however, tonus is coregulated by endothelial cells (EC) and pericytes. In the microcirculation, pericyte dysfunction contributes to several debilitating vascular pathologies, including diabetic retinopathy (DR), hypertension, atherosclerosis, ischemia, stroke, asthma, and Alzheimer's disease (10,13,30,53).A growing body of evidence in pericyte pathophysiology indicates that pericytes play a critical role in the maintenance of capillary EC (CEC) physiology and angiogenic induction (2,12,16,38). For example, in the retina, perturbations in pericyte-EC interactions can result in pathological angiogenesis accompanying proliferative DR (2, 13, 21).…”

mentioning

confidence: 99%

mentioning

confidence: 99%

Pericyte contractility controls endothelial cell cycle progression and sprouting: insights into angiogenic switch mechanics

Durham

Surks

Dulmovits

et al. 2014

American Journal of Physiology-Cell Physiology

View full text Add to dashboard Cite

Durham JT, Surks HK, Dulmovits BM, Herman IM. Pericyte contractility controls endothelial cell cycle progression and sprouting: insights into angiogenic switch mechanics. Am J Physiol Cell Physiol 307: C878 -C892, 2014. First published August 20, 2014; doi:10.1152/ajpcell.00185.2014.-Microvascular stability and regulation of capillary tonus are regulated by pericytes and their interactions with endothelial cells (EC). While the RhoA/Rho kinase (ROCK) pathway has been implicated in modulation of pericyte contractility, in part via regulation of the myosin light chain phosphatase (MLCP), the mechanisms linking Rho GTPase activity with actomyosin-based contraction and the cytoskeleton are equivocal. Recently, the myosin phosphatase-RhoA-interacting protein (MRIP) was shown to mediate the RhoA/ROCK-directed MLCP inactivation in vascular smooth muscle. Here we report that MRIP directly interacts with the ␤-actinspecific capping protein ␤cap73. Furthermore, manipulation of MRIP expression influences pericyte contractility, with MRIP silencing inducing cytoskeletal remodeling and cellular hypertrophy. MRIP knockdown induces a repositioning of ␤cap73 from the leading edge to stress fibers; thus MRIP-silenced pericytes increase F-actin-driven cell spreading twofold. These hypertrophied and cytoskeleton-enriched pericytes demonstrate a 2.2-fold increase in contractility upon MRIP knockdown when cells are plated on a deformable substrate. In turn, silencing pericyte MRIP significantly affects EC cycle progression and angiogenic activation. When MRIP-silenced pericytes are cocultured with capillary EC, there is a 2.0-fold increase in EC cycle entry. Furthermore, in three-dimensional models of injury and repair, silencing pericyte MRIP results in a 1.6-fold elevation of total tube area due to EC network formation and increased angiogenic sprouting. The pivotal role of MRIP expression in governing pericyte contractile phenotype and endothelial growth should lend important new insights into how chemomechanical signaling pathways control the "angiogenic switch" and pathological angiogenic induction. cytoskeleton; Rho kinase; myosin light chain phosphatase; myosin light chain; capillary; mural cell; angiogenesis IN ARTERIES AND VEINS, vascular tone is largely regulated via vascular smooth muscle. In capillaries and venules, however, tonus is coregulated by endothelial cells (EC) and pericytes. In the microcirculation, pericyte dysfunction contributes to several debilitating vascular pathologies, including diabetic retinopathy (DR), hypertension, atherosclerosis, ischemia, stroke, asthma, and Alzheimer's disease (10,13,30,53).A growing body of evidence in pericyte pathophysiology indicates that pericytes play a critical role in the maintenance of capillary EC (CEC) physiology and angiogenic induction (2,12,16,38). For example, in the retina, perturbations in pericyte-EC interactions can result in pathological angiogenesis accompanying proliferative DR (2, 13, 21). The notion has been widely held that, early in DR, vascular cell ...

show abstract

Parenchymal pericytes are not the major contributor of extracellular matrix in the fibrotic scar after stroke in male mice

Roth

Enström

Aghabeick

et al. 2019

J of Neuroscience Research

View full text Add to dashboard Cite

Scar formation after injury of the brain or spinal cord is a common event. While glial scar formation by astrocytes has been extensively studied, much less is known about the fibrotic scar, in particular after stroke. Platelet‐derived growth factor receptor ß‐expressing (PDGFRß+) pericytes have been suggested as a source of the fibrotic scar depositing fibrous extracellular matrix (ECM) proteins after detaching from the vessel wall. However, to what extent these parenchymal PDGFRß+ cells contribute to the fibrotic scar and whether targeting these cells affects fibrotic scar formation in stroke is still unclear. Here, we utilize male transgenic mice that after a permanent middle cerebral artery occlusion stroke model have a shift from a parenchymal to a perivascular location of PDGFRß+ cells due to the loss of regulator of G‐protein signaling 5 in pericytes. We find that only a small fraction of parenchymal PDGFRß+ cells co‐label with type I collagen and fibronectin. Consequently, a reduction in parenchymal PDGFRß+ cells by ca. 50% did not affect the overall type I collagen or fibronectin deposition after stroke. The redistribution of PDGFRß+ cells to a perivascular location, however, resulted in a reduced thickening of the vascular basement membrane and changed the temporal dynamics of glial scar maturation after stroke. We demonstrate that parenchymal PDGFRß+ cells are not the main contributor to the fibrotic ECM, and therefore targeting these cells might not impact on fibrotic scar formation after stroke.

show abstract

The Possible Roles of Brain Pericytes in Brain Ischemia and Stroke

Cited by 39 publications

References 86 publications

Nox4 Is a Major Source of Superoxide Production in Human Brain Pericytes

Nox4 Is a Major Source of Superoxide Production in Human Brain Pericytes

Pericyte contractility controls endothelial cell cycle progression and sprouting: insights into angiogenic switch mechanics

Parenchymal pericytes are not the major contributor of extracellular matrix in the fibrotic scar after stroke in male mice

Contact Info

Product

Resources

About