Blood flow-dependent arterial remodelling is facilitated by inflammation but directed by vascular tone

Bakker, Erik N. T. P.; Matlung, Hanke L.; Bonta, Peter I.; Vries, Carlie J.M. de; Rooijen, Nico van; VanBavel, Ed

doi:10.1093/cvr/cvn050

Cited by 81 publications

(104 citation statements)

References 29 publications

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“…This environment is likely to result in the differentiation of both M1 and M2 macrophages, similar to what we recently reported for the mixed Th1/Th2 environment during pulmonary Cryptococcus neoformans infections (1). IL-4 and IL-10 are potent drivers of M2 differentiation and M2-derived factors (such as matrix metalloproteinase-9 and factor XIIIA), as well as M1-derived molecules (such as inducible nitric oxide synthase [iNOS] and tumor necrosis factor alpha [TNF-␣]), and are constituents of actively remodeling arterial environments (2,14,28,45). Macrophages are welldocumented central mediators of arterial remodeling in experimental atherosclerosis in apolipoprotein E knockout mice, and in these mice, there is an early influx of M2 followed by a late influx of M1 macrophages into atherosclerotic plaques (24).…”

Section: Discussionmentioning

confidence: 99%

Repeated Exposure to Aspergillus fumigatus Conidia Results in CD4⁺T Cell-Dependent and -Independent Pulmonary Arterial Remodeling in a Mixed Th1/Th2/Th17 Microenvironment That Requires Interleukin-4 (IL-4) and IL-10

et al. 2012

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Pulmonary arterial remodeling is a pathological process seen in a number of clinical disease states, driven by inflammatory cells and mediators in the remodeled artery microenvironment. In murine models, Th2 cell-mediated immune responses to inhaled antigens, such as purified Aspergillus allergen, have been reported to induce remodeling of pulmonary arteries. We have previously shown that repeated intranasal exposure of healthy C57BL/6 mice to viable, resting Aspergillus fumigatus conidia leads to the development of chronic pulmonary inflammation and the coevolution of Th1, Th2, and Th17 responses in the lungs. Our objective was to determine whether repeated intranasal exposure to Aspergillus conidia would induce pulmonary arterial remodeling in this mixed Th inflammatory microenvironment. Using weekly intranasal conidial challenges, mice developed robust pulmonary arterial remodeling after eight exposures (but not after two or four). The process was partially mediated by CD4 ؉ T cells and by interleukin-4 (IL-4) production, did not require eosinophils, and was independent of gamma interferon (IFN-␥) and IL-17. Furthermore, remodeling could occur even in the presence of strong Th1 and Th17 responses. Rather than serving an antiinflammatory function, IL-10 was required for the development of the Th2 response to A. fumigatus conidia. However, in contrast to previous studies of pulmonary arterial remodeling driven by the A. fumigatus allergen, viable conidia also stimulated pulmonary arterial remodeling in the absence of CD4 ؉ T cells. Remodeling was completely abrogated in IL-10 ؊/؊ mice, suggesting that a second, CD4 ؉ T cell-independent, IL-10-dependent pathway was also driving pulmonary arterial remodeling in response to repeated conidial exposure.

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Section: Discussionmentioning

confidence: 99%

Repeated Exposure to Aspergillus fumigatus Conidia Results in CD4⁺T Cell-Dependent and -Independent Pulmonary Arterial Remodeling in a Mixed Th1/Th2/Th17 Microenvironment That Requires Interleukin-4 (IL-4) and IL-10

et al. 2012

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“…This is in agreement with our previous studies showing the involvement of the system in response to acute changes in flow in vitro 14 -16 or in vivo 35 in the mesenteric vascular bed. Indeed, an early stimulation of the local production of angiotensin II could have a role in the inflammatory response necessary for the remodeling, 36 because angiotensin II may stimulate the production of monocyte chemoattractant protein 1. 37 Nevertheless, this issue remains to be further investigated.…”

Section: Discussionmentioning

confidence: 99%

Role of Angiotensin II in the Remodeling Induced by a Chronic Increase in Flow in Rat Mesenteric Resistance Arteries

et al. 2010

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Abstract-Angiotensin II is a potent growth factor involved in arterial wall homeostasis. In resistance arteries, chronic increases in blood flow induce a rise in diameter associated with arterial wall hypertrophy. Nevertheless, the role of angiotensin II in this remodeling is unknown. We investigated the effect of blocking angiotensin II production or receptor activation on flow-induced remodeling of mesenteric resistance arteries. Arteries were ligated in vivo to generate high-flow arteries compared with normal flow (control) vessels located at a distance. Arteries were isolated after 1 week for in vitro analysis. Arterial diameter, media surface, endothelial NO synthase expression, superoxide production, and extracellular signal-regulated kinase 1/2 phosphorylation were higher in high-flow than in control arteries. Angiotensin-converting enzyme inhibition (perindopril) and angiotensin II type 1 receptor blockade (candesartan) prevented arterial wall hypertrophy without affecting diameter enlargement. The nonselective vasodilator hydralazine had no effect on remodeling. Although perindopril and candesartan increased endothelial NO synthase expression in high-flow arteries, hypertrophy remained in rats treated with N G -nitro-L-arginine methyl ester and mice lacking endothelial NO synthase. Perindopril and candesartan reduced oxidative stress in high-flow arteries, but superoxide scavenging did not prevent hypertrophy. Both Tempol and the absence of endothelial NO synthase prevented the rise in diameter in high-flow vessels. Extracellular signal-regulated kinase 1/2 activation in high-flow arteries was prevented by perindopril and candesartan and not by hydralazine. Extracellular signal-regulated kinase 1/2 inhibition in vivo (U0126) prevented hypertrophy in high-flow arteries. Thus, a chronic rise in blood flow in resistance arteries induces a diameter enlargement involving NO and superoxide, whereas hypertrophy was associated with extracellular signal-regulated kinase 1/2 activation by angiotensin II. (Hypertension. 2010;55:109-115.) Key Words: resistance arteries Ⅲ blood flow Ⅲ angiotensin II Ⅲ ERK1/2 Ⅲ shear stress Ⅲ angiotensin I-converting enzyme inhibitors Ⅲ angiotensin II type 1 receptor inhibitor A ngiotensin II is a potent vasoactive hormone involved in the regulation of vascular tone, 1,2 in cell growth and apoptosis, 3 and in cell migration and extracellular matrix deposition. 4 Angiotensin II also has a central role in the functional and structural integrity of the vascular wall and in the pathogenesis of cardiovascular diseases. [5][6][7] Chronic changes in blood flow occur in physiological conditions, such as exercise, pregnancy, or postnatal development, and in pathological conditions, such as arterial occlusive diseases, diabetes mellitus, or hypertension. 1,8 A chronic increase in blood flow induces remodeling of the vascular wall to adapt arterial wall strain to the new hemodynamic conditions, as described in large blood vessels 9 and in small resistance arteries. 1,8 Indeed, in resistance art...

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“…In vivo studies investigating the role of the actin cytoskeleton on inward remodeling within the resistance vasculature are limited. In comparison, a number of in vivo studies have shown a role for transglutaminases in resistance vessel remodeling in response to changes in flow (1,3); in response to a 1-wk infusion of the nitric oxide (NO) synthase (NOS) inhibitor N -nitro-L-arginine methyl ester hydrochloride (L-NAME) (41); and in response to a 1-wk infusion of phenylephrine (13). An important limitation in the majority of these in vivo studies is that the experimental designs did not allow for differentiation between the effects produced by blood pressure and vasoconstriction on the development of inward remodeling.…”

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confidence: 99%

Brief serotonin exposure initiates arteriolar inward remodeling processes in vivo that involve transglutaminase activation and actin cytoskeleton reorganization

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Castorena‐Gonzalez

Staiculescu

et al. 2016

American Journal of Physiology-Heart and Circulatory Physiology

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LA. Brief serotonin exposure initiates arteriolar inward remodeling processes in vivo that involve transglutaminase activation and actin cytoskeleton reorganization. Am J Physiol Heart Circ Physiol 310: H188 -H198, 2016. First published November 11, 2015; doi:10.1152/ajpheart.00666.2015.-Inward remodeling of the resistance vasculature is strongly associated with life-threatening cardiovascular events. Previous studies have demonstrated that both actin polymerization and the activation of transglutaminases mediate early stages of the transition from a structurally normal vessel to an inwardly remodeled one. Ex vivo studies further suggest that a few hours of exposure to vasoconstrictor agonists induces inward remodeling in the absence of changes in intraluminal pressure. Here we report that a short, 10-min, topical exposure to serotonin (5-HT) ϩ N -nitro-L-arginine methyl ester hydrochloride (L-NAME) was sufficient to initiate inward remodeling processes in rat cremasteric feed arterioles (100 -200 m lumen diameter), in vivo. Addition of the transglutaminase inhibitor, cystamine, blocked the in vivo remodeling. We further demonstrate that, in isolated arterioles, 5-HT ϩ L-NAME activates transglutaminases and modulates the phosphorylation state of cofilin, a regulator of actin depolymerization. The 5-HT ϩ L-NAME-induced remodeling process in isolated arterioles was also inhibited by an inhibitor of Lim Kinase, the kinase that phosphorylates and inactivates cofilin. Therefore, our results indicate that a brief vasoconstriction induced by 5-HT ϩ L-NAME is able to reduce the passive structural diameter of arterioles through processes that are dependent on the activation of transglutaminases and Lim kinase, and the subsequent phosphorylation of cofilin. inward remodeling; cytoskeleton; hypertension; vasospasm; vasoconstriction; nitric oxide NEW & NOTEWORTHYUsing intravital microscopy, we demonstrate that a brief exposure of the resistance vasculature to vasoconstrictors initiates inward remodeling processes, in vivo, via mechanism(s) that include the activation of transglutaminases and the reorganization of the actin cytoskeleton. This is the first study to examine the process in vivo, in real time.INWARD REMODELING OF THE RESISTANCE vasculature is a hallmark feature of a number of cardiovascular diseases including hypertension (31). The marked increase in the risk for lifethreatening cardiovascular events associated with inward remodeling (6, 34, 42) highlights its clinical importance. In addition, inward eutrophic remodeling of the resistance vasculature is believed to play an important role in increasing peripheral vascular resistance and decreasing tissue blood flow during the development and maintenance of essential hypertension (15). Inward remodeling is defined as a decrease in the luminal diameter of blood vessels under passive conditions (38). In essential hypertension, this remodeling is eutrophic; that is, there is no significant change in the cross-sectional area of the vascular wall, which indicates the...

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Blood flow-dependent arterial remodelling is facilitated by inflammation but directed by vascular tone

Abstract: Altered blood flow triggers an inflammatory response that facilitates remodelling. Vascular tone is a crucial determinant of the direction of the remodelling response.

Cited by 81 publications

References 29 publications

Repeated Exposure to Aspergillus fumigatus Conidia Results in CD4⁺T Cell-Dependent and -Independent Pulmonary Arterial Remodeling in a Mixed Th1/Th2/Th17 Microenvironment That Requires Interleukin-4 (IL-4) and IL-10

Repeated Exposure to Aspergillus fumigatus Conidia Results in CD4⁺T Cell-Dependent and -Independent Pulmonary Arterial Remodeling in a Mixed Th1/Th2/Th17 Microenvironment That Requires Interleukin-4 (IL-4) and IL-10

Role of Angiotensin II in the Remodeling Induced by a Chronic Increase in Flow in Rat Mesenteric Resistance Arteries

Brief serotonin exposure initiates arteriolar inward remodeling processes in vivo that involve transglutaminase activation and actin cytoskeleton reorganization

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Blood flow-dependent arterial remodelling is facilitated by inflammation but directed by vascular tone

Abstract: Altered blood flow triggers an inflammatory response that facilitates remodelling. Vascular tone is a crucial determinant of the direction of the remodelling response.

Cited by 81 publications

References 29 publications

Repeated Exposure to Aspergillus fumigatus Conidia Results in CD4+T Cell-Dependent and -Independent Pulmonary Arterial Remodeling in a Mixed Th1/Th2/Th17 Microenvironment That Requires Interleukin-4 (IL-4) and IL-10

Repeated Exposure to Aspergillus fumigatus Conidia Results in CD4+T Cell-Dependent and -Independent Pulmonary Arterial Remodeling in a Mixed Th1/Th2/Th17 Microenvironment That Requires Interleukin-4 (IL-4) and IL-10

Role of Angiotensin II in the Remodeling Induced by a Chronic Increase in Flow in Rat Mesenteric Resistance Arteries

Brief serotonin exposure initiates arteriolar inward remodeling processes in vivo that involve transglutaminase activation and actin cytoskeleton reorganization

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Repeated Exposure to Aspergillus fumigatus Conidia Results in CD4⁺T Cell-Dependent and -Independent Pulmonary Arterial Remodeling in a Mixed Th1/Th2/Th17 Microenvironment That Requires Interleukin-4 (IL-4) and IL-10

Repeated Exposure to Aspergillus fumigatus Conidia Results in CD4⁺T Cell-Dependent and -Independent Pulmonary Arterial Remodeling in a Mixed Th1/Th2/Th17 Microenvironment That Requires Interleukin-4 (IL-4) and IL-10