A Model for Geometric and Mechanical Adaptation of Arteries to Sustained Hypertension

Rachev, Alexander; Stergiopulos, Nikolaos; Meister, J.‐J.

doi:10.1115/1.2834313

Cited by 107 publications

(89 citation statements)

References 23 publications

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“…As a result, it has been difficult to mathematically model time courses of changes in cellular and matrix activity, which is essential for understanding how the arterial wall responds to hypertension (Rachev et al 1998;Gleason and Humphrey 2004). One goal of this work, therefore, was to quantify together the time courses of cellular and matrix changes in the aorta of a single model of hypertension over an extended (8 week) period.…”

Section: Discussionmentioning

confidence: 99%

Time Courses of Growth and Remodeling of Porcine Aortic Media During Hypertension: A Quantitative Immunohistochemical Examination

Ambrus

Fossum

et al. 2007

J Histochem Cytochem.

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(EW) S U M M A R Y Arteries undergo marked structural and functional changes in human and experimental hypertension that generally involve smooth muscle cell (SMC) hypertrophy/ hyperplasia as well as abnormal extracellular matrix turnover. In this study we examined time courses of changes in SMC activity and matrix protein content in a novel mini-pig aortic coarctation model. Cell proliferation was evaluated by immunostaining of Ki-67, apoptosis was assessed by TUNEL, and phenotypic changes were monitored by immunostaining three SMC contractile markers (caldesmon, calponin, and smoothelin). Changes in medial collagen and elastin were examined by picrosirius red and Verhoeff-van Gieson staining, respectively. LabVIEW-based image analysis routines were developed to objectively and efficiently quantify the (immuno)histochemical results. We found that significant cell proliferation and matrix production occurred in the early stages of this coarctation model and then declined gradually; the SMCs also tended to exhibit a less contractile phenotype following these cellular and extracellular changes. Specifically, different aspects of the phenotypic changes associated with hypertension occurred at different rates: cell proliferation and collagen production occurred early and peaked by 2 weeks, whereas changes in contractile protein expression continued to decrease over the entire 8-week study period. Temporal changes found in this study emphasize the importance of simultaneously tracing time courses of SMC growth and differentiation as well as matrix protein production and content. SMCs are multifunctional, and caution must be used to not overdefine phenotype. This manuscript contains online supplemental material at http://www.jhc.org. Please visit this article online to view these materials. (J Histochem Cytochem 56:359-370, 2008)

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Section: Discussionmentioning

confidence: 99%

Time Courses of Growth and Remodeling of Porcine Aortic Media During Hypertension: A Quantitative Immunohistochemical Examination

Ambrus

Fossum

et al. 2007

J Histochem Cytochem.

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“…In the model of Taber and Eggers (1996), circumferential and radial growth depends on local wall stress. The models of Taber (1998), Rachev et al (1998), andHumphrey (2001) grow in response to both wall stress and the fluid shear stress on the endothelium. Rachev and Hayashi (1999) added a contractile term for more acute shear stress management.…”

Section: Discussionmentioning

confidence: 99%

Growth and remodeling in a thick-walled artery model: effects of spatial variations in wall constituents

Alford

Humphrey

Taber

2007

Biomech Model Mechanobiol

144

118

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A mathematical model is presented for growth and remodeling of arteries. The model is a thickwalled tube composed of a constrained mixture of smooth muscle cells, elastin and collagen. Material properties and radial and axial distributions of each constituent are prescribed according to previously published data. The analysis includes stress-dependent growth and contractility of the muscle and turnover of collagen fibers. Simulations were conducted for homeostatic conditions and for the temporal response following sudden hypertension. Numerical pressure-radius relations and opening angles (residual stress) show reasonable agreement with published experimental results. In particular, for realistic material and structural properties, the model predicts measured variations in opening angles along the length of the aorta with reasonable accuracy. These results provide a better understanding of the determinants of residual stress in arteries and could lend insight into the importance of constituent distributions in both natural and tissue-engineered blood vessels.

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“…It is well thought that arterial growth and remodeling in response to changes in blood flow, blood pressure, and axial stretch leads to geometric and material adaptations that restore the wall shear stress (33), circumferential (hoop) stress (4), cyclic circumferential strain (45), and axial stress (32) to target values.…”

Section: H678 Elastic Fibers and Mechanics Of Carotid Arteries In Matmentioning

confidence: 99%

Dysfunction in elastic fiber formation in fibulin-5 null mice abrogates the evolution in mechanical response of carotid arteries during maturation

Wan

Gleason

2013

American Journal of Physiology-Heart and Circulatory Physiology

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Wan W, Gleason RL, Jr. Dysfunction in elastic fiber formation in fibulin-5 null mice abrogates the evolution in mechanical response of carotid arteries during maturation. Am J Physiol Heart Circ Physiol 304: H674 -H686, 2013. First published December 15, 2012 doi:10.1152/ajpheart.00459.2012.-Elastin fragmentation is a common characteristic of vascular diseases, such as abdominal aortic aneurysms, peripheral arterial disease, and aortic dissection. Examining growth and remodeling in the presence of dysfunctional elastic fibers provides insight into the adaptive or maladaptive changes that tissues undergo in compensating for structural deficiencies. This study used the maturation of fibulin-5 knockout (KO) and wild-type mice to study the effects of fragmented elastic fibers on the growth and remodeling of carotid arteries. The microstructural content and organization and the biaxial mechanical behavior of common carotid arteries were measured, and parameter estimation performed from KO and WT mice aged 3, 4, 8, and 13 wk. Gross measurements and biaxial tests revealed significant differences in pressure-diameter behavior, in vivo axial stretch, opening angle, compliance, and wall stresses during maturation of wild-type arteries, but little change in these values in KO mice. Multiphoton microscopy used to image collagen fibers across the vessel wall in pressurized and stretched arteries suggests that there is little variation in fiber angles between different ages. Parameter estimation revealed significant differences in material parameters between genotypes and age groups. This study suggests that neonatal formation and cross-linking of functional elastic fibers, followed by increases in artery size due to growth with little remodeling of the elastic fibers, endow arteries with large distensibility and contribute to the evolution of mechanical behavior of arteries during maturation. Dysfunction in neonatal formation of elastic fibers abrogates many of the changes in mechanical response that take place during the maturation. artery mechanics; extracellular matrix; elastin; arterial stiffening; fbln5 LOSS OF FUNCTIONAL ELASTIC fibers is associated with various vascular diseases, including abdominal aortic aneurysms (5, 46), peripheral arterial disease (42, 43), aortic dissection (30, 49), as well as pathologies in other organ systems (13,20). Fibulin-5 (fbln5) is an extracellular matrix protein that binds to integrins and localizes tropoelastin to microfibrils (39, 62). In humans, altered expression of fbln5 is correlated with a variety of diseases, such as thoracic aortic dissection (59), age-related macular degeneration (52), as well as various cancers (26,36,63). Fbln5 knockout (KO) mice exhibit loose skin, pelvic organ prolapse, and tortuous arteries with disrupted elastic lamellae (39,62). Previous studies have shown that arteries from adult fbln5 KO mice have altered biomechanical and microstructural properties, including disrupted and dysfunctional elastic lamellae (58); however, evolution of biomechanical an...

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A Model for Geometric and Mechanical Adaptation of Arteries to Sustained Hypertension

Cited by 107 publications

References 23 publications

Time Courses of Growth and Remodeling of Porcine Aortic Media During Hypertension: A Quantitative Immunohistochemical Examination

Time Courses of Growth and Remodeling of Porcine Aortic Media During Hypertension: A Quantitative Immunohistochemical Examination

Growth and remodeling in a thick-walled artery model: effects of spatial variations in wall constituents

Dysfunction in elastic fiber formation in fibulin-5 null mice abrogates the evolution in mechanical response of carotid arteries during maturation

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