Molecular basis of the effects of mechanical stretch on vascular smooth muscle cells

Haga, Jason; Li, Yi-Shuan J.; Chien, Shu

doi:10.1016/j.jbiomech.2006.04.011

Cited by 291 publications

(251 citation statements)

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“…Finally, increased wall stress causes pathologic remodeling in systemic arteries. [73][74][75][76][77] Note that intravascular pressure is not the only plausible relevant mechanical force. The cross-sectional area of the pulmonary vascular bed is presumably reduced with PVHincreased PVR, implying (absent lower flow) that shear stress is increased.…”

Section: Wall Stress and Pvh-phmentioning

confidence: 99%

“…Definitive confirmation and characterization of the role-and possible pharmacologic modulation-of myogenic tone in PVH-PH will likely have to wait until selective antagonists for stretch-operated channels and/or other components of the machinery of mechanically induced contractile activation are developed. 74,80 Alas, our fragmentary understanding of the molecular mechanisms underlying the SMC stretch response seriously constrains our ability to better characterize it in vivo and manipulate it. Although investigators have learned a lot about how mechanical forces are translated into biological effect in SMC, a granular picture of the mechanisms involved has yet to evolve.…”

Section: Myogenic Vasoconstrictionmentioning

confidence: 99%

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Pulmonary Hypertension Caused by Pulmonary Venous Hypertension

Kulik

2014

Pulm. circ.

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The effect of pulmonary venous hypertension (PVH) on the pulmonary circulation is extraordinarily variable, ranging from no impact on pulmonary vascular resistance (PVR) to a marked increase. The reasons for this are unknown. Both acutely reversible pulmonary vasoconstriction and pathological remodeling (especially medial hypertrophy and intimal hyperplasia) account for increased PVR when present. The mechanisms involved in vasoconstriction and remodeling are not clearly defined, but increased wall stress, especially in small pulmonary arteries, presumably plays an important role. Myogenic contraction may account for increased vascular tone and also indirectly stimulate remodeling of the vessel wall. Increased wall stress may also directly cause smooth muscle growth, migration, and intimal hyperplasia. Even long-standing and severe pulmonary hypertension (PH) usually abates with elimination of PVH, but PVH-PH is an important clinical problem, especially because PVH due to left ventricular noncompliance lacks definitive therapy. The role of targeted PH therapy in patients with PVH-PH is unclear at this time. Most prospective studies indicate that these medications are not helpful or worse, but there is ample reason to think that a subset of patients with PVH-PH may benefit from phosphodiesterase inhibitors or other agents. A different approach to evaluating possible pharmacologic therapy for PVH-PH may be required to better define its possible utility.Keywords: pulmonary hypertension, pulmonary venous hypertension. As a perfect example of how clinical imperative can drive basic physiological investigation, studies of the effect of pulmonary venous hypertension (PVH) on the lung's circulation were in full swing by the very early 1950s, 1 close on the heels of the development of surgical relief of mitral valve stenosis. Cardiac catheterization of patients with mitral valve disease has characterized the physiology of PVH, and histological investigations demonstrated the microvascular changes provoked by PVH. Just as important, the effect of relief of left atrial (LA) hypertension on the circulation has been extensively reported, usually for patients who have had mitral valve intervention. We have learned that the circulatory alterations provoked by PVH share some characteristics with other forms of pulmonary hypertension (PH), such as the idiopathic variety, PH due to chronic alveolar hypoxia, and PH secondary to congenital cardiac shunting lesions. For example, acute "reactivity" to vasodilators may be observed, and there is overlap in the microarchitectural abnormalities seen. On the other hand, the "natural history" of PVH-PH is very different than that of the idiopathic variety or that seen with shunting defects: in the former (as demonstrated with mitral valve disease), PH is likely to largely or completely resolve if PVH is relieved, even with long-standing and severely increased pulmonary vascular resistance (PVR), 2,3 while in the latter two, PH is more likely to inexorably increase. PVH-PH is ther...

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Section: Wall Stress and Pvh-phmentioning

confidence: 99%

Section: Myogenic Vasoconstrictionmentioning

confidence: 99%

Pulmonary Hypertension Caused by Pulmonary Venous Hypertension

Kulik

2014

Pulm. circ.

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“…(g ) Flow, shear and cyclic strain Endothelial cells and VSMCs are exposed to shear stress and cyclic stretch, and are able to detect changes in these forces, transducing them via signalling cascades and gene expression to a cellular response tailored to alter vessel architecture in order to normalize these forces (Grimm et al 2005;Haga et al 2007). Shear stress is an important factor in determining a vessel's propensity to develop atherosclerosis and restenosis post-stenting.…”

Section: (F ) Remodellingmentioning

confidence: 99%

The application of multiscale modelling to the process of development and prevention of stenosis in a stented coronary artery

Evans

Lawford

Gunn

et al. 2008

Phil. Trans. R. Soc. A.

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The inherent complexity of biomedical systems is well recognized; they are multiscale, multiscience systems, bridging a wide range of temporal and spatial scales. While the importance of multiscale modelling in this context is increasingly recognized, there is little underpinning literature on the methodology and generic description of the process. The COAST (complex autonoma simulation technique) project aims to address this by developing a multiscale, multiscience framework, coined complex autonoma (CxA), based on a hierarchical aggregation of coupled cellular automata (CA) and agent-based models (ABMs). The key tenet of COAST is that a multiscale system can be decomposed into N single-scale CA or ABMs that mutually interact across the scales. Decomposition is facilitated by building a scale separation map on which each single-scale system is represented according to its spatial and temporal characteristics. Processes having wellseparated scales are thus easily identified as the components of the multiscale model. This paper focuses on methodology, introduces the concept of the CxA and demonstrates its use in the generation of a multiscale model of the physical and biological processes implicated in a challenging and clinically relevant problem, namely coronary artery in-stent restenosis.

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“…Like myocardium, the surrounding bones may act as support and reduce the expansion of the vertebral arteries, thereby reducing the local TS and protecting the arteries from atherosclerosis. On the other hand, at the segment proximal to the bridge, the local TS is higher than the tunnelled segment and may cause structural and functional changes of vascular cells (endothelial cells and primarily smooth muscle cells), ultimately resulting in the formation of atherosclerotic lesions (19) (Figure 2). At the molecular level, the higher TS is sensed by several endothelial mechanoreceptors, such as integrins, stretch-sensitive ion channels, tyrosine kinase receptors and G-proteins, which trigger a complex network of downstream signalling cascades of serine kinases (mitogen-activated protein kinases), eventually leading to activation of transcription factors (eg, nuclear factor kappa B or activator protein-1) (19).…”

Section: Role Of Tensile Stressmentioning

confidence: 99%