Connexin43 Is Highly Localized to Sites of Disturbed Flow in Rat Aortic Endothelium but Connexin37 and Connexin40 Are More Uniformly Distributed

Gabriels, Joseph; Paul, David L.

doi:10.1161/01.res.83.6.636

Cited by 254 publications

(259 citation statements)

References 38 publications

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“…In gap junctions, laminar shear stress transiently increases the expression of connexin 43, while disturbed flow sustains the induction of connexin 43 but disorganizes the cell-cell communication [Cowan et al, 1998;Gabriels and Paul, 1998;DePaola et al, 1999]. In tight junctions, shear stress increases occludin phosphorylation and decreases occludin expression, which may be responsible for the increase of hydraulic conductivity of an EC monolayer [DeMaio et al, 2001].…”

Section: Cell-cell Adhesions In Shear Stress-induced Ec Migrationmentioning

confidence: 99%

Mechanotransduction in endothelial cell migration

Li¹,

Huang²,

Hsu³

2005

J of Cellular Biochemistry

239

180

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The migration of endothelial cells (ECs) plays an important role in vascular remodeling and regeneration. EC migration can be regulated by different mechanisms such as chemotaxis, haptotaxis, and mechanotaxis. This review will focus on fluid shear stress-induced mechanotransduction during EC migration. EC migration and mechanotransduction can be modulated by cytoskeleton, cell surface receptors such as integrins and proteoglycans, the chemical and physical properties of extracellular matrix (ECM) and cell-cell adhesions. The shear stress applied on the luminal surface of ECs can be sensed by cell membrane and associated receptor and transmitted throughout the cell to cell-ECM adhesions and cell-cell adhesions. As a result, shear stress induces directional migration of ECs by promoting lamellipodial protrusion and the formation of focal adhesions (FAs) at the front in the flow direction and the disassembly of FAs at the rear. Persistent EC migration in the flow direction can be driven by polarized activation of signaling molecules and the positive feedback loops constituted by Rho GTPases, cytoskeleton, and FAs at the leading edge. Furthermore, shear stressinduced EC migration can overcome the haptotaxis of ECs. Given the hemodynamic environment of the vascular system, mechanotransduction during EC migration has a significant impact on vascular development, angiogenesis, and vascular wound healing.

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Section: Cell-cell Adhesions In Shear Stress-induced Ec Migrationmentioning

confidence: 99%

Mechanotransduction in endothelial cell migration

Li¹,

Huang²,

Hsu³

2005

J of Cellular Biochemistry

239

180

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“…Individually, these proteins form channels with different physiological properties (1)(2)(3). However, these connexins have all been found within the same cell type (the endothelial cell), and in a number of cases they can be identified within the same individual cell (4)(5)(6). The relative abundance of these connexins varies in different endothelia.…”

Section: Introductionmentioning

confidence: 99%

Modulation of intercellular communication by differential regulation and heteromeric mixing of co-expressed connexins

Beyer

Gemel

Seul

et al. 2000

Braz J Med Biol Res

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Intercellular communication may be regulated by the differential expression of subunit gap junction proteins (connexins) which form channels with differing gating and permeability properties. Endothelial cells express three different connexins (connexin37, connexin40, and connexin43) in vivo. To study the differential regulation of expression and synthesis of connexin37 and connexin43, we used cultured bovine aortic endothelial cells which contain these two connexins in vitro. RNA blots demonstrated discordant expression of these two connexins during growth to confluency. RNA blots and immunoblots showed that levels of these connexins were modulated by treatment of cultures with transforming growth factor-ß1. To examine the potential ability of these connexins to form heteromeric channels (containing different connexins within the same hemi-channel), we stably transfected connexin43-containing normal rat kidney (NRK) cells with connexin37 or connexin40. In the transfected cells, both connexin proteins were abundantly produced and localized in identical distributions as detected by immunofluorescence. Double whole-cell patch-clamp studies showed that co-expressing cells exhibited unitary channel conductances and gating characteristics that could not be explained by hemi-channels formed of either connexin alone. These observations suggest that these connexins can readily mix with connexin43 to form heteromeric channels and that the intercellular communication between cells is determined not only by the properties of individual connexins, but also by the interactions of those connexins to form heteromeric channels with novel properties. Furthermore, modulation of levels of the co-expressed connexins during cell proliferation or by cytokines may alter the relative abundance of different heteromeric combinations.

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“…In vascular cells, four connexins have been found, namely Cx43, Cx40, Cx37, and Cx45 (8). Of these, Cx43 is the most abundant within the vascular smooth muscle, whereas Cx40 is mainly found in the endothelium (1,12,24,27,31).…”

mentioning

confidence: 99%

Lack of vascular connexin 40 is associated with hypertension and irregular arteriolar vasomotion

Wit

Roos

Bolz

et al. 2003

Physiological Genomics

184

154

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Gap-junctional communication coordinates the behavior of individual cells in arterioles. Gap junctions are formed by connexins 40 (Cx40), Cx43, Cx37, and Cx45 in the vasculature. Previously, we have shown that lack of Cx40 impairs conduction of dilatory signals along arterioles. Herein, we examined whether hypertension is present in conscious animals and whether this is a direct effect or due to secondary mechanisms. Mean arterial pressure was elevated by 20–25 mmHg in conscious Cx40-deficient mice (Cx40−/−) compared with wild-type controls in both sexes. Differences in heart rate were not observed. Blockade of NO synthase increased pressure equally in both genotypes. Conversely, the angiotensin AT1-receptor antagonist, candesartan, decreased pressure to similar extents in Cx40−/− and wild-type mice. Acetylcholine and sodium nitroprusside (0.05–15 nmol) were equally potent and effective in decreasing pressure and inducing dilatory responses in the microcirculation. However, in contrast to wild type, Cx40−/− arterioles exhibited spontaneous, irregular vasomotion leading temporarily to complete vessel closure. We conclude that loss of Cx40 is associated with hypertension independent of the action of angiotensin II. It is also not related to an altered efficacy of NO or other endothelial dilators. However, the observed irregular vasomotion suggests that peripheral vascular resistance is affected.

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Connexin43 Is Highly Localized to Sites of Disturbed Flow in Rat Aortic Endothelium but Connexin37 and Connexin40 Are More Uniformly Distributed

Cited by 254 publications

References 38 publications

Mechanotransduction in endothelial cell migration

Mechanotransduction in endothelial cell migration

Modulation of intercellular communication by differential regulation and heteromeric mixing of co-expressed connexins

Lack of vascular connexin 40 is associated with hypertension and irregular arteriolar vasomotion

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