41 research outputs found
A Dynamic Stochastic Model of Frequency-Dependent Stress Fiber Alignment Induced by Cyclic Stretch
BACKGROUND: Actin stress fibers (SFs) are mechanosensitive structural elements that respond to forces to affect cell morphology, migration, signal transduction and cell function. Cells are internally stressed so that SFs are extended beyond their unloaded lengths, and SFs tend to self-adjust to an equilibrium level of extension. While there is much evidence that cells reorganize their SFs in response to matrix deformations, it is unclear how cells and their SFs determine their specific response to particular spatiotemporal changes in the matrix. METHODOLOGY/PRINCIPAL FINDINGS: Bovine aortic endothelial cells were subjected to cyclic uniaxial stretch over a range of frequencies to quantify the rate and extent of stress fiber alignment. At a frequency of 1 Hz, SFs predominantly oriented perpendicular to stretch, while at 0.1 Hz the extent of SF alignment was markedly reduced and at 0.01 Hz there was no alignment at all. The results were interpreted using a simple kinematic model of SF networks in which the dynamic response depended on the rates of matrix stretching, SF turnover, and SF self-adjustment of extension. For these cells, the model predicted a threshold frequency of 0.01 Hz below which SFs no longer respond to matrix stretch, and a saturation frequency of 1 Hz above which no additional SF alignment would occur. The model also accurately described the dependence of SF alignment on matrix stretch magnitude. CONCLUSIONS: The dynamic stochastic model was capable of describing SF reorganization in response to diverse temporal and spatial patterns of stretch. The model predicted that at high frequencies, SFs preferentially disassembled in the direction of stretch and achieved a new equilibrium by accumulating in the direction of lowest stretch. At low stretch frequencies, SFs self-adjusted to dissipate the effects of matrix stretch. Thus, SF turnover and self-adjustment are each important mechanisms that cells use to maintain mechanical homeostasis
Carotid stenosis - Factors affecting symptomatology
Background and Purpose-The ability to predict future strokes in
asymptomatic patients with carotid stenosis is currently limited. The
management of symptomatic patients with < 50% stenosis is also
debatable, In this context, we performed the following open prospective
study to identify factors affecting symptomatology in patients with
carotid stenosis.
Methods-During 1988-1997, 442 arteries with various degrees of stenosis
were followed with the use of color Duplex ultrasonography every 6
months. The main outcome measures were development of symptoms related
to the carotid territory and progression in the degree of stenosis.
Results Of follow-up were analyzed in relation to the traditional risk
factors for atherosclerosis as well as the ultrasonographic
characteristics of the plaques. Statistical analysis was performed by
multiple linear and Cox regression analysis. Results-Mean duration of
follow-up was 44 months (range, 12 to 120 months). Significant
progression of stenosis occurred in 18.5% of the cases and was more
frequent in younger patients (P = 0.09), in patients with coronary
artery disease (P = 0.02), and in patients with echolucent plaques (P =
0.02), In regard to clinical presentation, men (P = 0.07), hypertensives
(P = 0.07), and patients with echolucent plaques (P = 0.09) showed a
trend toward higher frequency of stroke in their history. During the
follow-up period. neurological events developed in 12.4% of the cases
and were associated with the severity of carotid disease (P < 0.001),
history of neurological events (P = 0.02), progression of stenosis (P =
0.002). echolucent plaques (P = 0.01). and hypertension (P = 0.02).
Conclusions-Factors other than de-ree of stenosis and history of
neurological events are also important in determining high-risk carotid
plaque. In our study hypertension. echolucent plaques, and progressive
lesions were associated with an increased risk of neurological events.
These factors should be taken into consideration in determining
treatment strategies for carotid stenosis
Artificial blood vessel: The Holy Grail of peripheral vascular surgery
Artificial blood vessels composed of viable tissue represent the ideal
vascular graft. Compliance, lack of thrombogenicity, and resistance to
infections as well as the ability to heal, remodel, contract, and
secrete normal blood vessel products are theoretical advantages of such
grafts. Three basic elements are generally required for the construction
of an artificial vessel: a structural scaffold, made either of collagen
or a biodegradable polymer; vascular cells, and a nurturing environment.
Mechanical properties of the artificial vessels are enhanced by
bioreactors that mimic the in vivo environment of the vascular cells by
producing pulsatile flow. Alternative approaches include the production
of fibrocollagenous tubes within the recipient’s own body (subcutaneous
tissue or peritoneal cavity) and the construction of an artificial
vessel from acellular native tissues, such as decellularized small
intestine submucosa, ureter, and allogeneic or xenogeneic arteries. This
review details the most recent developments on vascular tissue
engineering, summarizes the results of initial experiments on animals
and humans, and outlines the current status and the challenges for the
future
Inflammation and atherosclerosis
Purpose. The aim of this article is to discuss the role of inflammation
in atherosclerosis.
Summary. An initial chemical, mechanical or immunological insult induces
endothelial dysfunction. This triggers a cascade of inflammatory
reactions, in Which monocytes, macrophages, T lymphocytes and vascular
smooth muscle cells participate. Leukocyte adhesion molecules,
cytokines, growth factors and metalloproteinases participate in all
stages of atherogenesis. Almost all of the traditional risk factors for
atherosclerosis are associated with and participate in the inflammatory
process. Many infectious agents, mainly Chlamydia pneumoniae, have been
proposed as potential triggers of the cascade. The immune system has
been implicated in plaque formation, through the activation of cellular
and humoral immunity against innate or microbial heat shock protein 60.
Methods of detection of systemic or local plaque inflammation have been
developed and research is being conducted on the potential use of
anti-inflammatory and antibiotic drugs in atherosclerosis
The role of STAT-3 in the mediation of smooth muscle cell response to cyclic strain
Hemodynamic forces, including shear stress and cyclic strain, have been
recognised as important modulators of vascular cell morphology and
function. However, the mechanism by which vascular cells sense and
transduce the extracellular mechanical signals into the cell nucleus has
not yet been clarified. The purpose of our study was to assess the
involvement of the signal transducer and activator of transcription-3
(STAT-3) in the signaling pathway mediating the response of vascular
smooth muscle cells (SMC) to cyclic strain. Embryonic A7r5 SMC derived
from thoracic aortas of DB 1X rats were seeded on flexible collagen
I-coated plates. Cells were subjected to 10% average strain at 60
cycles/min for various time periods. Activation of STAT-3, p38,
extracellular signal -regulated kinase (ERK) 1/2 and Src was assessed by
immunoblotting using phosphospecific antibodies. The interactions
between STAT-3 phosphorylation and p38, ERK 1 /2, phosphatidylinositol-3
(PI3K), mammalian target of rapamycin (mTOR), Janus kinase (JAK) 2 and
Src were evaluated by pretreating the cells with specific inhibitors
including SB202190, PD98059, LY294002, wortmannin, rapamycin, AG490 and
PP I.
Serine phosphorylation of STAT-3 was increased by 2-fold after 15 min of
cyclic strain, while tyrosine phosphorylation was increased by 2.3-fold
after 60 min. Inhibition of ERK 1/2 by PD98059 prevented serine
phosphorylation of STAT-3, whereas inhibition of Src by PP1 prevented
STAT-3 tyrosine phosphorylation. Pretreating the cells with SB202190, a
specific inhibitor of p38, resulted in an increase in basal
phosphorylation of ERK1/2 and a subsequent increase in basal serine
phosphorylation of STAT-3.
In conclusion, both serine and tyrosine phosphorylation of STAT-3 are
involved in the signaling pathway mediating the effects of cyclic strain
on vascular SMC. Serine phosphorylation of STAT-3 is mediated by ERK1/2,
while tyrosine phosphorylation is mediated by Re. A negative feedback
loop was also found between p38 and ERK 1 /2. (c) 2005 Elsevier Ltd. All
rights reserved
Risk factors associated with recurrent carotid artery stenosis
The aim of this open, perspective study was to determine the impact of
risk factors, excluding the type of closure of the arteriotomy, in the
development of recurrent carotid stenosis following carotid
endarterectomy. One hundred and ninety-eight patients, who underwent a
total of 221 carotid endarterectomies, were evaluated postoperatively
with duplex scanning 1 month after the operation and every 6 months
thereafter for a period of 6-120 months (mean duration of follow-up: 44
months). There were 149 (75.3%) men and 49 (24.7%) women with a mean
age of 66.8 years (age range 38-92 years). Diabetes mellitus was present
in 62 patients (31.3%), hypertension in 134 (67.7%), coronary artery
disease in 130 (65.7%), hypercholesterolemia in 70 (35.4%), and
smoking habit in 166 (83.8%). Indications for carotid endarterectomy
were asymptomatic carotid stenosis > 70% in 20 (10.1%) patients and
symptomatic stenosis > 50% in 178 (89.9%), 129 (65.2%) of whom had a
history of transient ischemic attacks and 49 (24.7%) of previous
stroke. General anesthesia was used in 197 (89.1%) operations and local
anesthesia in 24 (10.9%). Deep endarterectomy with primary closure of
the arteriotomy using 5/0 running suture was performed in this group of
patients.
One patient: (0.5%) died during the perioperative period. Five (2.5%)
patients had a transient ischemic attack and three (1.5%) a nonfatal
stroke in the immediate postoperative period, six (3.0%) a persistent
cranial nerve injury, and two a hematoma, and three patients had delayed
postoperative recovery. Twenty-six (13.1%) patients were transferred to
the Intensive Care Unit postoperatively, Recurrent carotid stenosis >
50% was identified in eight patients (4.0%) and it was asymptomatic in
all cases; Mean interval between endarterectomy and development of
restenosis was 47.4 months (range 6-118 months). Factors such as
clinical presentation, age, sex, diabetes mellitus, hypertension,
coronary artery disease, hypercholesterolemia, and smoking habit were
not found to be significantly associated with the development: of
restenosis (Chi-square). Smoking, coronary artery disease, and normal
choresterol levels were connected with a statistically nonsignificant
tendency toward higher rates of restenosis. Recurrent carotid stenosis
following carotid endarterectomy was not significantly associated with
any of the risk factors studied in this series