A Structure-Based Model of Arterial Remodeling in Response to Sustained Hypertension

2009 ◽  
Vol 131 (10) ◽  
Author(s):  
Alkiviadis Tsamis ◽  
Nikos Stergiopulos ◽  
Alexander Rachev
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Time Course ◽  
Arterial Compliance ◽  
Experimental Studies ◽  
Wall Stress ◽  
Muscle Cells ◽  
Collagen Fibers ◽  
Opening Angle ◽  
Arterial Remodeling

A novel structure-based mathematical model of arterial remodeling in response to a sustained increase in pressure is proposed. The model includes two major aspects of remodeling in a healthy matured vessel. First, the deviation of the wall stress and flow-induced shear stress from their normal physiological values drives the changes in the arterial geometry. Second, the new mass that is produced during remodeling results from an increase in the mass of smooth muscle cells and collagen fibers. The model additionally accounts for the effect of the average pulsatile strain on the recruitment of collagen fibers in load bearing. The model was used to simulate remodeling of a human thoracic aorta, and the results are in good agreement with previously published model predictions and experimental data. The model predicts that the total arterial volume rapidly increases during the early stages of remodeling and remains virtually constant thereafter, despite the continuing stress-driven geometrical remodeling. Moreover, the effects of a perfect or incomplete restoration of the arterial compliance on the remodeling outputs were analyzed. For instance, the model predicts that the pattern of the time course of the opening angle depends on the extent to which the average pulsatile strain is restored at the end of the remodeling process. Future experimental studies on the time course of compliance, opening angle, and mass fractions of collagen, elastin, and smooth muscle cells can validate and improve the introduced hypotheses of the model.

scholarly journals Time-Course Analysis on the Differentiation of Bone Marrow-Derived Progenitor Cells Into Smooth Muscle Cells During Neointima Formation

2010 ◽  
Vol 30 (10) ◽  
pp. 1890-1896 ◽  
Author(s):  
Jan-Marcus Daniel ◽  
Wiebke Bielenberg ◽  
Philipp Stieger ◽  
Soenke Weinert ◽  
Harald Tillmanns ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Progenitor Cells ◽  
Time Course ◽  
Muscle Cells ◽  
Neointima Formation

scholarly journals Combination of histochemical analyses and micro-MRI reveals regional changes of the murine cervix in preparation for labor

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Antara Chatterjee ◽  
Rojan Saghian ◽  
Anna Dorogin ◽  
Lindsay S. Cahill ◽  
John G. Sled ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Diffusion Tensor ◽  
Ex Vivo ◽  
Muscle Cells ◽  
Pregnant Mouse ◽  
Collagen Fibers ◽  
Muscular Layer ◽  
Tissue Organization ◽  
Picrosirius Red

AbstractThe cervix is responsible for maintaining pregnancy, and its timely remodeling is essential for the proper delivery of a baby. Cervical insufficiency, or “weakness”, may lead to preterm birth, which causes infant morbidities and mortalities worldwide. We used a mouse model of pregnancy and term labor, to examine the cervical structure by histology (Masson Trichome and Picrosirius Red staining), immunohistochemistry (Hyaluronic Acid Binding Protein/HABP), and ex-vivo MRI (T2-weighted and diffusion tensor imaging), focusing on two regions of the cervix (i.e., endocervix and ectocervix). Our results show that mouse endocervix has a higher proportion of smooth muscle cells and collagen fibers per area, with more compact tissue structure, than the ectocervix. With advanced gestation, endocervical changes, indicative of impending delivery, are manifested in fewer smooth muscle cells, expansion of the extracellular space, and lower presence of collagen fibers. MRI detected three distinctive zones in pregnant mouse endocervix: (1) inner collagenous layer, (2) middle circular muscular layer, and (3) outer longitudinal muscular layer. Diffusion MRI images detected changes in tissue organization as gestation progressed suggesting the potential application of this technique to non-invasively monitor cervical changes that precede the onset of labor in women at risk for preterm delivery.

Elevated levels of activin A in clinical and experimental pulmonary hypertension

2009 ◽  
Vol 106 (4) ◽  
pp. 1356-1364 ◽  
Author(s):  
Arne Yndestad ◽  
Karl-Otto Larsen ◽  
Erik Øie ◽  
Thor Ueland ◽  
Camilla Smith ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Transforming Growth Factor ◽  
Experimental Studies ◽  
Plasminogen Activator Inhibitor ◽  
Muscle Cells ◽  
Activin A ◽  
Plasminogen Activator Inhibitor 1 ◽  
And Control

Activin A, a member of the transforming growth factor (TGF)-β superfamily, is involved in regulation of tissue remodeling and inflammation. Herein, we wanted to explore a role for activin A in pulmonary hypertension (PH). Circulating levels of activin A and its binding protein follistatin were measured in patients with PH ( n = 47) and control subjects ( n = 14). To investigate synthesis and localization of pulmonary activin A, we utilized an experimental model of hypoxia-induced PH. In mouse lungs, we also explored signaling pathways that can be activated by activin A, such as phosphorylation of Smads, which are mediators of TGF-β signaling. Possible pathophysiological mechanisms initiated by activin A were explored by exposing pulmonary arterial smooth muscle cells in culture to this cytokine. Elevated levels of activin A and follistatin were found in patients with PH, and activin A levels were significantly related to mortality. Immunohistochemistry of lung autopsies from PH patients and lungs with experimental PH localized activin A primarily to alveolar macrophages and bronchial epithelial cells. Mice with PH exhibited increased pulmonary levels of mRNA for activin A and follistatin in the lungs, and also elevated pulmonary levels of phosphorylated Smad2. Finally, we found that activin A increased proliferation and induced gene expression of endothelin-1 and plasminogen activator inhibitor-1 in pulmonary artery smooth muscle cells, mediators that could contribute to vascular remodeling. Our findings in both clinical and experimental studies suggest a role for activin A in the development of various types of PH.

Voltage-dependent calcium channel current in isolated gallbladder smooth muscle cells of guinea pig

1993 ◽  
Vol 264 (6) ◽  
pp. G1066-G1076 ◽  
Author(s):  
T. Shimada
Keyword(s):  
Smooth Muscle ◽  
Guinea Pig ◽  
Smooth Muscle Cells ◽  
Time Course ◽  
Reversal Potential ◽  
High Sensitivity ◽  
Muscle Cells ◽  
Patch Clamp Technique ◽  
Decay Component ◽  
Voltage Dependent

The voltage-dependent Ca2+ current was studied in enzymatically dispersed guinea pig gallbladder smooth muscle cells using the whole cell patch-clamp technique. Depolarizing voltage (V) steps induced an inward current (I) that was carried by Ca2+. The threshold potential was -40 to -30 mV, the maximal current was observed at +10 to +20 mV, and the reversal potential was around +80 mV. I-V curves obtained with holding potentials of -80 and -40 mV were not significantly different. This current had a high sensitivity to dihydropyridine drugs, and the Ba2+ or Sr2+ current was larger than the Ca2+ current. Activation was accelerated by increasing the membrane potential. In general, the time course of decay was well fitted by the sum of two exponentials, but consideration of a third (ultra-slow) decay component was also necessary when the current generated by a 2-s command pulse was analyzed. Superimposition of activation and inactivation curves showed the presence of a significant window current. Carbachol suppressed the Ca2+ current only when the pipette contained a low concentration of ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid. These results show that the L-type Ca2+ current is dominant in gallbladder smooth muscle cells and may contribute to excitation-contraction coupling.

Patchy Deletion Of Bmpr1a In Smooth Muscle Cells Potentiates Chronic Hypoxia-Induced Proximal Arterial Remodeling

2011 ◽  
Author(s):  
Rebecca R. Vanderpool ◽  
Nesrine El-Bizri ◽  
Marlene Rabinovitch ◽  
Naomi C. Chesler
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Chronic Hypoxia ◽  
Muscle Cells ◽  
Arterial Remodeling

Calcium sensitivity of vasospastic basilar artery after experimental subarachnoid hemorrhage

2006 ◽  
Vol 290 (6) ◽  
pp. H2329-H2336 ◽  
Author(s):  
R. Loch Macdonald ◽  
Zhen-Du Zhang ◽  
Masataka Takahashi ◽  
Elena Nikitina ◽  
J. Young ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Subarachnoid Hemorrhage ◽  
Smooth Muscle Cells ◽  
Arterial Wall ◽  
Arterial Compliance ◽  
Smooth Muscle Actin ◽  
Muscle Cells ◽  
Calcium Sensitivity ◽  
Basilar Arteries

Arteries that develop vasospasm after subarachnoid hemorrhage (SAH) may have altered contractility and compliance. Whether these changes are due to alterations in the smooth muscle cells or the arterial wall extracellular matrix is unknown. This study elucidated the location of such changes and determined the calcium sensitivity of vasospastic arteries. Dogs were placed under general anesthesia and underwent creation of SAH using the double-hemorrhage model. Vasospasm was assessed by angiography performed before and 4, 7, or 21 days after SAH. Basilar arteries were excised from SAH or control dogs ( n = 8–52 arterial rings from 2–9 dogs per measurement) and studied under isometric tension in vitro before and after permeabilization of smooth muscle with α-toxin. Endothelium was removed from all arteries. Vasospastic arteries demonstrated significantly reduced contractility to KCl with a shift in the EC50 toward reduced sensitivity to KCl 4 and 7 days after SAH ( P < 0.05, ANOVA). There was reduced compliance that persisted after permeabilization ( P < 0.05, ANOVA). Calcium sensitivity was decreased during vasospasm 4 and 7 days after SAH, as assessed in permeabilized arteries and in those contracted with BAY K 8644 in the presence of different concentrations of extracellular calcium ( P < 0.05, ANOVA). Depolymerization of actin with cytochalasin D abolished contractions to KCl but failed to alter arterial compliance. In conclusion, it is shown for the first time that calcium sensitivity is decreased during vasospasm after SAH in dogs, suggesting that other mechanisms are involved in maintaining the contraction. Reduced compliance seems to be due to an alteration in the arterial wall extracellullar matrix rather than the smooth muscle cells themselves because it cannot be alleviated by depolymerization of smooth muscle actin.

scholarly journals Changes in the components of extracellular matrix and in growth properties of cultured aortic smooth muscle cells upon ascorbate feeding.

1982 ◽  
Vol 92 (2) ◽  
pp. 462-470 ◽  
Author(s):  
E Schwartz ◽  
R S Bienkowski ◽  
B Coltoff-Schiller ◽  
S Goldfischer ◽  
O O Blumenfeld
Keyword(s):  
Extracellular Matrix ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Time Course ◽  
Cultured Cells ◽  
Growth Parameters ◽  
Muscle Cells ◽  
Cellular Protein ◽  
Collagen Accumulation ◽  
The Matrix

Culture conditions can modify the composition of the extracellular matrix of cultured calf aortas smooth muscle cells. In the absence of ascorbate the major components of the matrix are microfibrillar proteins; deposition of collagen occurs upon ascorbate supplementation and, with increased time of exposure of cells to ascorbate, collagen becomes the dominant protein of the extracellular matrix (greater than 80%). Collagen accumulation follows a sigmoidal time-course, suggesting that it is a cooperative phenomenon. Covalent crosslinks are not required for collagen accumulation in the matrix. Microfibrillar proteins and increased amounts of proteoglycans and fibronectin accumulate concurrently with collagen but elastin deposition was not observed either with or without ascorbate feeding. Addition of ascorbate leads to a general stimulation of incorporation of [14C]proline into cellular protein and to changes in cell growth parameters and morphology: cell-doubling time decreases from 62 to 47 h and plating efficiency increases approximately fourfold. We conclude that the composition of the extracellular matrix assembled by cultured cells is subject to experimental manipulation and that changes in endogenously deposited matrix may have significant effects on cellular functions.

Abstract P511: Targeting Il-1β Protects From Aortic Aneurysms Induced by Disrupted Tgfβ Signaling in Smooth Muscle Cells

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Daniela Carnevale ◽  
Raimondo Carnevale ◽  
Francesco Da Ros ◽  
Roberta Iacobucci ◽  
Manuel Casaburo ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Time Course ◽  
Molecular Mechanisms ◽  
Muscle Cells ◽  
Ascending Aorta ◽  
Aortic Aneurysms ◽  
Tgfβ Signaling ◽  
Aneurysm Formation ◽  
Aortic Pathology

Aortic aneurysms represent a life-threatening condition because of the current lack of effective treatments. Aneurysm formation is typically associated with extracellular matrix remodeling and persistent inflammation. Although the molecular mechanisms underlying aortic pathology remain largely unclear, TGFβ signaling is unquestionably implied and its downstream target Smad4 showed protective functions for maintenance of aortic walls’ integrity. Using mice with smooth muscle cells (SMCs) specific deletion of Smad4 in the adult ( Smad4 -SMC iko ), developing spontaneous aneurysms (Ascending Aorta Diameter: Smad4 -SMC iko 2.15±0.03; Smad4 -SMC wt 1.7±0.03;***p< 0.001), we investigated the molecular mechanisms activated by dysregulation of TGFβ signaling. Structural disarrangement of ascending aorta in Smad4 -SMC iko mice was clearly appreciated early after Smad4 deletion as discrete breaks of elastic lamellae (breaks/section: Smad4 -SMC iko 2.05±0.5; Smad4 -SMC wt 0.83±0.4;***p< 0.001). Interestingly, the islands of damage in the aorta of Smad4 -SMC iko were enriched of immune infiltrate, mainly monocytes/macrophages, as indicated by FACS and immunofluorescence. We then analyzed several pathways downstream to Smad4 inhibition, finding a selective activation of NF-kB/IL-1β in SMCs. To test the relevance of this pathway in the formation of aneurysms, we deleted Smad4 in SMCs of mice with Il1r1 null background ( Smad4 -SMC iko ; Il1r1 -/- ). Ultrasonographic analyses revealed that ablation of IL1 receptor1 protected Smad4 -SMC iko mice from the progression of pathology and improved their overall survival. In the end, to test the translational potential of our findings, we neutralized IL-1β signaling with the clinically relevant murine version of the FDA-approved clinical drug canakinumab. During a time course of 16 weeks, while a weekly administration of control immunoglobulins did not change aneurysm progression in Smad4 -SMC iko mice, treatment with anti-IL-1β antibody significantly hampered aneurysm formation in the aorta ( Smad4 -SMC iko +anti- IL-1β 1.85±0.02; Smad4 -SMC iko +anti-IgG 2.09±0.03; ***p< 0.001) These findings identify a mechanistic target for controlling aneurysms progression induced by disrupted TGFβ signaling.

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