Structural adaptation increases predicted perfusion capacity after vessel obstruction in arteriolar arcade network of pig skeletal muscle

Gruionu, Gabriel; Hoying, James B.; Gruionu, Lucian Gheorghe; Laughlin, M. Harold; Secomb, Timothy W.

doi:10.1152/ajpheart.00917.2004

Cited by 16 publications

(20 citation statements)

References 40 publications

(38 reference statements)

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“…In vivo, a delicate balance between these stimuli, integrated through SMC activation, governs local perfusion. As indicated by the present simulations and by in vitro (36,43), as well as in vivo (11,19,37,44,45) and model (19,26,38), studies, a more protracted disturbance of this balance may lead to vascular remodeling. One possible advantage of SMC activation being a longterm regulated variable would be that in vivo deviation from the habitual level of activation may provide the vascular wall with an unambiguous signal guiding the direction of the remodeling to arrive at a structure where blood flow can match a changed tissue demand.…”

Section: Critique Of the Modelsupporting

confidence: 58%

A mechanism for arteriolar remodeling based on maintenance of smooth muscle cell activation

Jacobsen¹,

Mulvany²,

Holstein‐Rathlou³

2008

American Journal of Physiology-Regulatory, Integrative and Comp

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Jacobsen JC, Mulvany MJ, Holstein-Rathlou N-H. A mechanism for arteriolar remodeling based on maintenance of smooth muscle cell activation. Am J Physiol Regul Integr Comp Physiol 294: R1379-R1389, 2008. First published January 9, 2008 doi:10.1152/ajpregu.00407.2007.-Structural adaptation in arterioles is part of normal vascular physiology but is also seen in disease states such as hypertension. Smooth muscle cell (SMC) activation has been shown to be central to microvascular remodeling. We hypothesize that, in a remodeling process driven by SMC activation, stress sensitivity of the vascular wall is a key element in the process of achieving a stable vascular structure. We address whether the adaptive changes in arterioles under different conditions can arise through a common mechanism: remodeling in a stress-sensitive wall driven by a shift in SMC activation. We present a simple dynamic model and show that structural remodeling of the vessel radius by rearrangement of the wall material around a lumen of a different diameter and driven by differences in SMC activation can lead to vascular structures similar to those observed experimentally under various conditions. The change in structure simultaneously leads to uniform levels of circumferential wall stress and wall strain, despite differences in transmural pressure. A simulated vasoconstriction caused by increased SMC activation leads to inward remodeling, whereas outward remodeling follows relaxation of the vascular wall. The results are independent of the specific myogenic properties of the vessel. The simulated results are robust in the face of parameter changes and, hence, may be generalized to vessels from different vascular beds. essential hypertension; microcirculation; eutrophic remodeling VESSELS OF THE MICROCIRCULATION must continuously meet the changing demands of the tissues. On short time scales, vascular diameter and, hence, tissue perfusion are regulated by variation in smooth muscle cell (SMC) activation. On longer time scales, resistance vessels adapt structurally to maintain dimensions optimal for acute flow regulation. In microvascular networks in vivo, such adaptation depends on a complex interplay between various stimuli, including pressure, shear stress, and metabolic status of the tissue (38).As noted six decades ago by Folkow and co-workers (15), in human essential hypertension, resistance vessels develop a reduced lumen size and an increased wall thickness. These changes are apparently caused by redistribution of the wall material around a smaller lumen, i.e., inward eutrophic remodeling (33), and allow the vessel to operate at normal or near-normal levels of activation, despite increased pressure (14).Another example of structural adaptation is the surprising observation by Bakker et al. (7) that, in unbranched segments of first-order rat cremaster arterioles, structural diameter does, in fact, increase distally along the vessel. This increase in diameter is not associated with an increase in wall transsectional area. Rather, analogous ...

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Section: Critique Of the Modelsupporting

confidence: 58%

A mechanism for arteriolar remodeling based on maintenance of smooth muscle cell activation

Jacobsen¹,

Mulvany²,

Holstein‐Rathlou³

2008

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Therefore, it is not surprising that forces exerted by blood and plasma would provide feedback control for formation of that vasculature. It has long been known that blood flow mediates remodeling of immature embryonic networks (35,36) and helps control vascular tone and collateral formation in muscle tissue (37,38). However, the role of fluid forces in the initiation of angiogenesis is not well understood, mainly due to a lack of appropriate tools for controlling the relevant parameters.…”

Section: Discussionmentioning

confidence: 99%

Fluid forces control endothelial sprouting

Song

Munn

2011

Proc. Natl. Acad. Sci. U.S.A.

443

459

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During angiogenesis, endothelial cells (ECs) from intact blood vessels quickly infiltrate avascular regions via vascular sprouting. This process is fundamental to many normal and pathological processes such as wound healing and tumor growth, but its initiation and control are poorly understood. Vascular endothelial cell growth factor (VEGF) can promote vessel dilation and angiogenic sprouting, but given the complex nature of vascular morphogenesis, additional signals are likely necessary to determine, for example, which vessel segments sprout, which dilate, and which remain quiescent. Fluid forces exerted by blood and plasma are prime candidates that might codirect these processes, but it is not known whether VEGF cooperates with mechanical fluid forces to mediate angiogenesis. Using a microfluidic tissue analog of angiogenic sprouting, we found that fluid shear stress, such as exerted by flowing blood, attenuates EC sprouting in a nitric oxide-dependent manner and that interstitial flow, such as produced by extravasating plasma, directs endothelial morphogenesis and sprout formation. Furthermore, positive VEGF gradients initiated sprouting but negative gradients inhibited sprouting, promoting instead sheet-like migration analogous to vessel dilation. These results suggest that ECs integrate signals from fluid forces and local VEGF gradients to achieve such varied goals as vessel dilation and sprouting.3D angiogenesis on a chip | collagen gel | structural remodeling | alternative to animal model | vessel analog A ngiogenesis, the expansion or extension of existing vasculature, is necessary to deliver oxygen and nutrients to ischemic or avascular regions in wounds and solid tumors (1), and a fundamental understanding of the determinants of angiogenesis would accelerate progress in the fields of regenerative medicine, tissue engineering, and oncology. Angiogenesis requires the coordinated growth and migration of endothelial cells (ECs): each EC residing in a vessel wall integrates local signals to determine whether it remains quiescent (2, 3), participates in dilation or contraction (1), undergoes morphogenesis to form an angiogenic sprout (4, 5), or intussusceptive involution (6). Implicit in these processes are endothelial proliferation during expansion of the vasculature and their loss during vessel contraction and pruning (7).Growth factors have pleiotropic effects on ECs and are undoubtedly key controllers of vascular morphogenesis. The best studied vascular morphogen, vascular endothelial growth factor (VEGF) (8), stimulates EC migration (9), proliferation (10), and matrix degradation (2). VEGF also controls vessel morphogenesis by inducing Delta-like ligand 4 (Dll4)-a membrane-bound ligand for the Notch family of receptors-at the advancing front of sprouts (11), thereby promoting the formation of specialized "tip cells," which extend protrusions or filopodia that sense growth factor concentrations to guide sprouts (4, 5). However, given the distinct phenotypes exhibited by ECs during sprouting, dilation, co...

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“…In the circulation, vascular elements are capable of structural remodeling in response to local stimuli including shear stress, intravascular pressure, and metabolic state of the tissue [1,2,7,8,11,15,18,19,26]. When blood flow to a part of a vascular network is interrupted, the remaining vessels may adapt to compensate for the decrease of blood supply [3,9,21–23].…”

Section: Introductionmentioning

confidence: 99%

Structural Remodeling of the Mouse Gracilis Artery: Coordinated Changes in Diameter and Medial Area Maintain Circumferential Stress

et al. 2012

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Objectives Vascular networks respond to chronic alterations in blood supply by structural remodeling. Previously, we showed that blood flow changes in the mouse gracilis artery lead to transient diameter increases, which can generate large increases in circumferential wall stress. Here, we examine the associated changes in the medial area of the arterial wall and the effects on circumferential wall stress. Methods To induce blood flow changes, one of the two feeding vessels to the gracilis artery was surgically removed. At 7 to 56 days after blood flow interruption, the vasculature was perfused with India ink for morphological measurements, and processed for immuno-cytochemistry to mark the medial cross-section area. Theoretical simulations of hemodynamics were used to analyze the data. Results During adaptive increases in vessel diameter, increases in medial area were observed, most strongly in the middle region of the artery. Simulations showed that this increase in medial area limits the increase in estimated circumferential stress during vascular adaptation to less than 50%, in contrast to an increase of up to 250% if the medial area had remained unchanged. Conclusions During vascular adaptation, increases in circumferential stress are limited by growth of the media coordinated with diameter changes.

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Structural adaptation increases predicted perfusion capacity after vessel obstruction in arteriolar arcade network of pig skeletal muscle

Cited by 16 publications

References 40 publications

A mechanism for arteriolar remodeling based on maintenance of smooth muscle cell activation

A mechanism for arteriolar remodeling based on maintenance of smooth muscle cell activation

Fluid forces control endothelial sprouting

Structural Remodeling of the Mouse Gracilis Artery: Coordinated Changes in Diameter and Medial Area Maintain Circumferential Stress

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