Components Of Arterial Wall Research Articles

Scleraxis Alters Arterial Smooth Muscle Phenotypic Switching and Exacerbates Arterial Stiffness

Arterial stiffness (AS) is an impairment in arterial relaxation and function in blood pressure regulation and is associated with the development of multiple cardiovascular diseases including hypertension, atherosclerosis, and adverse outcomes such as stroke, heart failure, and death. AS comprises an increase in vascular wall components (extracellular matrix proteins or vascular smooth muscle cell (VSMC) composition) or cellular malfunction, or a combination of these factors. Preliminary data from our lab showed that using the Transverse Aortic Constriction (TAC) model, the transcription factor scleraxis is upregulated in the aortic wall on the pre-TAC/high pressure side versus post-TAC/low pressure side. Scleraxis also induces cellular phenotype activation of fibroblasts to myofibroblasts in cardiac fibrosis and mediates epithelial to mesenchymal transition in development. Angiotensin II (AngII) induces hypertension and increases stiffness in arteries, and we found that it also up-regulates scleraxis expression, suggesting the possibility that scleraxis may alter arterial wall composition. In this study, we investigated the role of scleraxis expression in VSMC, and its effect when over-expressed along with AngII treatment in small resistance arteries and aorta. In vivo, we upregulated scleraxis in VSMC using a Cre/LoxP approach and the tamoxifen-inducible Myh11cre mouse, with or without AngII delivery by micro-osmotic pump, then isolated 3rd order mesenteric arteries and assessed arterial function and stiffness by pressure myography. We harvested aortas for immunohistology staining and gene expression analysis. In vitro, we upregulated scleraxis in VSMC with or without AngII treatment and measured their proliferation by flow cytometry. Our findings show that scleraxis induces stiffness in mesenteric arteries, but not aorta by induction of VSMC proliferation. Scleraxis upregulation with AngII infusion exacerbates vascular stiffness in mesenteric arteries due to significant changes in arterial wall components, reducing internal lumen diameter and smooth muscle relaxation. At the molecular level, extracellular matrix protein expression is reduced in aortas. In in vitro studies, scleraxis-AngII treated VSMC exhibit lower proliferative capacity, distinct morphological changes and higher contractile gene expression, indicative of a hypertrophic contractile phenotype altering overall arterial stiffness. Our study shows that scleraxis alone can induce AS by regulating VSMC phenotype toward proliferation. In contrast, arterial stiffness is exacerbated in scleraxis overexpression and AngII-infused vessels by inducing VSMC towards a hypertrophic contractile phenotype. Therefore, scleraxis alters vascular smooth muscle phenotypic switching and arterial stiffness through different mechanisms, depending on the presence of AngII, which may have different pathological impacts depending on the specific underlying conditions. This work is supported by funding from Heart & Stroke Foundation and BMO Studentship. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Abstract 454: The Effect Of High-fat Diet On Vascular Smooth Muscle Cell Mechanics And Migration In Apoe -/- Mice

Atherosclerosis remains a leading cause of cardiovascular diseases, which cause causes about 30% of global death. Vascular smooth muscle cells (VSMCs) are the major cellular components of arterial wall. VMSCs play critical role in the atherosclerosis development by phenotypic switching from a contractile phenotype to a synthetic phenotype, migration from media to intima of arterial wall, and deposition as foam cells in atherosclerotic plaque. In this study, we tested the effect of high-fat diet on the VSMC mechanics by comparing the mechanics and migration of VSMCs isolated from apolipoprotein-E knockout (ApoE -/- ) and wild type (WT) mice. Atomic force microscope (AFM) was employed to test cell adhesion and stiffness of VSMCs. AFM was also used to examine live VSMC submembranous cytoskeleton organization. A data-driven mathematical models-based image and signal processing software was used to analyze AFM data. Two-way ANOVA was used to test statistical significance for all experiments. The results demonstrated significant differences in the actin cytoskeletal organization and cell mechanics between ApoE -/- VSMCs and WT cells upon high-fat diet. However, no significant difference in cell stiffness was observed between normal diet-fed ApoE -/- and WT VSMCs. These interesting findings on the effect of high-fat diet on VSMC mechanics will improve our knowledge of the mechanism underlying the contribution of VSMC in the development of atherosclerosis.

Animal models for large vessel vasculitis - The unmet need.

Our understanding of the pathogenesis of large vessel vasculitis (LVV) are mainly achieved by studying the arteries taken from temporal artery biopsy in giant cell arteries (GCA) or surgical or autopsy specimens in Takayasu arteritis (TAK). These artery specimens provide invaluable information about pathological changes in these conditions that GCA and TAK are similar but are distinctly different in immune cell infiltrate and distribution of inflammatory cells in anatomical locations. However, these specimens of established arteritis do not provide information of the arteritis initiation and early events which are impossible to obtain in human artery specimens. Animal models for LVV are needed but not available. Here, several approaches are proposed for experimentation to generate animal models to aid in delineating the interaction of immune reaction with arterial wall components.

MRI-based mechanical analysis of carotid atherosclerotic plaque using a material-property-mapping approach: A material-property-mapping method for plaque stress analysis

Background and objectiveAtherosclerosis is a major underlying cause of cardiovascular conditions. In order to understand the biomechanics involved in the generation and rupture of atherosclerotic plaques, numerical analysis methods have been widely used. However, several factors limit the practical use of this information in a clinical setting. One of the key challenges in finite element analysis (FEA) is the reconstruction of the structure and the generation of a mesh. The complexity of the shapes associated with carotid plaques, including multiple components, makes the generation of meshes for biomechanical computation a difficult and in some cases, an impossible task. To address these challenges, in this study, we propose a novel material-property-mapping method for carotid atherosclerotic plaque stress analysis that aims to simplify the process. MethodsThe different carotid plaque components were identified and segmented using magnetic resonance imaging (MRI). For the mapping method, this information was used in conjunction with an in-house code, which provided the coordinates for each pixel/voxel and tissue type within a predetermined region of interest. These coordinates were utilized to assign specific material properties to each element in the volume mesh which provides a region of transition. The proposed method was subsequently compared to the traditional method, which involves creating a composed mesh for the arterial wall and plaque components, based on its location and size. ResultsThe comparison between the proposed material-property-mapping method and the traditional method was performed in 2D, 3D structural-only, and fluid-structure interaction (FSI) simulations in terms of stress, wall shear stress (WSS), time-averaged WSS (TAWSS), and oscillatory shear index (OSI). The stress contours from both methods were found to be similar, although the proposed method tended to produce lower local maximum stress values. The WSS contours were also in agreement between the two methods. The velocity contours generated by the proposed method were verified against phase-contrast magnetic resonance imaging (MRI) measurements, for a higher level of confidence. ConclusionThis study shows that a material-property-mapping method can effectively be used for analyzing the biomechanics of carotid plaques in a patient-specific manner. This approach has the potential to streamline the process of creating volume meshes for complex biological structures, such as carotid plaques, and to provide a more efficient and less labor-intensive method.

Abstract 314: The Alteration In Cell Mechanics In Atherosclerosis

Atherosclerosis remains a major cause of cardiovascular disease. It is well known that the cholesterol accumulated in the macrophage-derived foam cells is the major component of atherosclerotic plaque. However, the growing evidence suggests that about 40% of the total foam cells in the atherosclerotic plaque were vascular smooth muscle cells (VSMCs)-derived. VSMCs are the major cellular components of arterial wall and undergo phenotypic switching from a functional contractile phenotype to a synthetic proliferative phenotype during the development of atherosclerosis. In addition, the surrounding environment of VSMCs within vascular wall changes with alterations in extracellular matrix (ECM) stiffness and composition. The main goal of this study is to test hypothesis that VSMC mechanics undergoes significant changes in response to these surrounding microenvironment alteration in the progression of atherosclerosis. We employed an innovative approach integrating a series of novel experimental approaches and data-driven mathematical models to monitor the real time mechanics of VSMCs isolated from western diet fed apolipoprotein-E knockout (ApoE -/- ) and wild type (WT) mice. The results demonstrated significant differences in the actin cytoskeletal organization and cell mechanics between ApoE -/- VSMCs and WT cells, which may trigger the VSMC migration and contribute to the formation of the arterial plaque. These interesting finding will lead to a novel therapeutic strategy for the pharmaceutical treatment of atherosclerosis by interfering the alteration in VSMC mechanics.

Callistephin inhibits amyloid-β protein aggregation and determined cytotoxicity against cerebrovascular smooth muscle cells as an in vitro model of cerebral amyloid angiopathy

It has been indicated that amyloid β (Aβ) plaques can be accumulated within the basement membranes of cerebrovascular smooth muscle cells (CVSMCs) and stimulate the induction of cerebral amyloid angiopathy (CAA). However, the exact mechanism(s) of which small molecules including callistephin mitigate the formation of Aβ aggregation and associated CAA is not well-understood. Therefore, in the present study, Aβ 1–42 samples in the aggregation buffer were co-incubated for 36 h without or with of callistephin and the protein aggregation features along with the associated cytotoxicity against CVSMCs as the core components of cerebral arterial wall were explored by different biochemical and cellular methods. Fluorescence (ThT, Nile red) and CD techniques indicated the inhibition of Aβ 1–42 fibrillization in the presence of callistephin. Cellular assays revealed that cytotoxicity of Aβ 1–42 samples aged in the aggregation buffer with callistephin was much less against CVSMCs than Aβ 1–42 amyloid alone through regulation of membrane leakage and downregulation of TNF-α and IL-6 at protein level. In conclusion, these data may provide useful information about the possible mechanisms by which callistephin can show its protective effect against CAA.

Multicomponent Mechanical Characterization of Atherosclerotic Human Coronary Arteries: An Experimental and Computational Hybrid Approach.

Atherosclerotic plaque rupture in coronary arteries, an important trigger of myocardial infarction, is shown to correlate with high levels of pressure-induced mechanical stresses in plaques. Finite element (FE) analyses are commonly used for plaque stress assessment. However, the required information of heterogenous material properties of atherosclerotic coronaries remains to be scarce. In this work, we characterized the component-wise mechanical properties of atherosclerotic human coronary arteries. To achieve this, we performed ex vivo inflation tests on post-mortem human coronary arteries and developed an inverse FE modeling (iFEM) pipeline, which combined high-frequency ultrasound deformation measurements, a high-field magnetic resonance-based artery composition characterization, and a machine learning-based Bayesian optimization (BO) with uniqueness assessment. By using the developed pipeline, 10 cross-sections from five atherosclerotic human coronary arteries were analyzed, and the Yeoh material model constants of the fibrous intima and arterial wall components were determined. This work outlines the developed pipeline and provides the knowledge of non-linear, multicomponent mechanical properties of atherosclerotic human coronary arteries.

Possibilities of Magnetic Resonance Imaging in the Diagnosis of Changes in the «Vascular Wall» in Giant Cell Arteritis

The aim of the study: to identify features of extracranial carotid and vertebral arteries vessel wall MRI in norm and pathology using layer-by-layer analysis of the arterial wall components. MRI results were compared at the same anatomical level with data of ultrasound examination of vertebral arteries in patients with giant cell arteritis and in health individuals. It was revealed that in normal arteries MRI signal from the vessel wall mainly formed by vascularized adventitia and venous plexuses. Media and intima visualization becomes possible in cases of their pathological transformation. Thus, it was defined which structures of the vessel wall take part in MRI signal forming in health individuals and patient with pathology. Also MRI patterns of different stages of large arteries vasculitis were identified.

Use of Human Umbilical Vein Endothelial Cells (HUVEC) as a Model to Study Cardiovascular Disease: A Review

Cardiovascular disease (CVD) is the leading cause of death worldwide, and extensive research has been performed to understand this disease better, using various experimental models. The endothelium plays a crucial role in the development of CVD, since it is an interface between bloodstream components, such as monocytes and platelets, and other arterial wall components. Human umbilical vein endothelial cell (HUVEC) isolation from umbilical cord was first described in 1973. To date, this model is still widely used because of the high HUVEC isolation success rate, and because HUVEC are an excellent model to study a broad array of diseases, including cardiovascular and metabolic diseases. We here review the history of HUVEC isolation, the HUVEC model over time, HUVEC culture characteristics and conditions, advantages and disadvantages of this model and finally, its applications in the area of cardiovascular diseases.

Optical coherence tomography-based patient-specific coronary artery reconstruction and fluid-structure interaction simulation.

Plaque rupture is related to the mechanical stress it suffered. The value and distribution of the mechanical stress in plaque could help on assessing plaque vulnerability. To look into the stress conditions in the coronary artery, a patient-specific coronary model was created by using optical coherence tomography (OCT) and angiography imaging data. The reconstructed coronary model consisted of the structure of the lumen, the arterial wall and plaque components. Benefited by the high resolution of OCT, detailed structures such as the thin fibrous cap could be observed and built into the geometry. On this reconstructed coronary model, a fully coupled fluid-structure interaction (FSI) simulation was performed. The principle stress in coronary plaque and the wall shear stress (WSS) were analyzed. The FSI simulation results show that the cap thickness had a significant effect on the stress, and the principle stress at the thin cap area was more than double of those at the locations with a larger thickness. WSS is thought as an important parameter to assess the potentially dangerous areas of the atherosclerosis-prone (caused by low WSS) and the plaque rupture (high WSS). From the WSS plots of our FSI model, the area with abnormal WSS value was detected around the position where a lipid core existed. The FSI simulation results were compared with the results from the conventional structure-only and the computational fluid dynamics (CFD)-only computational models to quantify the difference between the three models. We found little difference in the principle stress results between the FSI and the structure-only model, but a significant difference between the FSI and the CFD-only model when looking into the WSS. The WSS values at the two observation spots from the CFD-only model were higher than the values from the FSI model by 17.95% and 22.66% in average, respectively. Furthermore, the FSI model detected more areas of low WSS, because the fluid domain could expand circumferentially when pressure loaded on the flexible arterial. This study suggests that OCT-based FSI model may be useful for plaque vulnerability assessment and it may be critical to perform the FSI simulation if an accurate WSS value is required.

Progressive changes of elastic moduli of arterial wall and atherosclerotic plaque components during plaque development in human coronary arteries.

Stiffness of the arterial wall and atherosclerotic plaque components is a determinant of the stress field within plaques, which has been suggested to be an indicator of plaque vulnerability. The diversity and inhomogeneous structure of atherosclerotic lesions complicate the characterization of plaque components. In the present study, stiffness of the arterial wall and atherosclerotic plaque components in human coronary arteries was examined in early and developed atherosclerotic lesions. The force-spectroscopy mode of the atomic force microscope and histological examination were used for determination of elastic moduli at specified locations within samples. Fibrous cap (E = 14.1 ± 3.8kPa) showed lower stiffness than the fibrous tissue beneath the lipid pool (E = 17.6 ± 3.2kPa). Calcification zones (E = 96.1 ± 18.8kPa) and lipid pools (E = 2.7 ± 1.8kPa) were the stiffest and softest components of atherosclerotic lesions, respectively. The increase of media stiffness (%44.8) and reduction of the elastic modulus of the internal elastic lamina (%28.9) was observed in coronary arteries. Moreover, significant differences were observed between the stiffness of medial layer in diseased parts and free-plaque segments in incomplete plaques of coronary arteries. Our results can be used for better understanding of remodeling mechanisms of the arterial wall with plaque development. Graphical abstract Stiffness alteration of the arterial wall and atherosclerotic plaque components with plaque development in coronary arteries.

Concentration-dependent effects of paeoniflorin on proliferation and apoptosis of vascular smooth muscle cells

Vascular smooth muscle cells (VSMCs) are an important component of arterial walls, and their dysfunction may serve an important role in the development of cardiovascular diseases, including atherosclerosis and restenosis. Paeoniflorin (PF) is a principal component of the commonly used traditional Chinese medicine, peonies. To the best of our knowledge, the effects of PF on apoptosis and proliferation of VSMCs and its underlying molecular mechanisms have not been widely reported. Therefore, the present study was designed to investigated this phenomenon. VSMCs were treated with different concentrations of PF (25, 50 and 100µg/ml) for 12, 24 or 48h. The data demonstrated that PF treatment not only significantly decreased cell viability and DNA synthesis but also blocked G0/G1 cell cycle progression. This effect was associated with a decreased expression of cyclin D1, cyclin E, cyclin‑dependent kinase (CDK)4 and CDK2 as well as an upregulation of p21. Notably, a significant concentration‑dependent decrease in the phosphorylation of p65 and nuclear factor of κ light polypeptide gene enhancer in B‑cells inhibitor‑α (IκBα) was observed. In addition, it was demonstrated that PF promoted the apoptosis of VSMCs, which was associated with the increased expression of caspases. In conclusion, PF inhibited the proliferation of VSMCs by downregulating proteins associated with the nuclear factor‑κB signaling pathway. Furthermore, it promoted the apoptosis of VSMCs by upregulating the expression of caspases. These results may be useful in improving the understanding of the molecular mechanisms underlying the apoptotic and anti‑proliferative effects of PF on VSMCs, and facilitate the development of novel treatments for cardiovascular diseases.

Elastic and Muscular Arteries Differ in Structure, Basal NO Production and Voltage-Gated Ca(2+)-Channels.

In the last decades, the search for mechanisms underlying progressive arterial stiffening and for interventions to avoid or reverse this process has gained much attention. In general, arterial stiffening displays regional variation and is, for example, during aging more prominent in elastic than in muscular arteries. We hypothesize that besides passive also active regulators of arterial compliance [i.e., endothelial and vascular smooth muscle cell (VSMC) function] differ between these arteries. Hence, it is conceivable that these vessel types will display different time frames of stiffening. To investigate this hypothesis segments of muscular arteries such as femoral and mesenteric arteries and elastic arteries such as the aorta and carotid artery were isolated from female C57Bl6 mice (5–6 months of age, n = 8). Both microscopy and passive stretching of the segments in a myograph confirmed that passive mechanical properties (elastin, collagen) of elastic and muscular arteries were significantly different. Endothelial function, more specifically basal nitric oxide (NO) efficacy, and VSMC function, more specifically L-type voltage-gated Ca2+ channel (VGCC)-mediated contractions, were determined by α1-adrenoceptor stimulation with phenylephrine (PE) and by gradual depolarization with elevated extracellular K+ in the absence and presence of eNOS inhibition with L-NAME. PE-mediated isometric contractions significantly increased after inhibition of NO release with L-NAME in elastic, but not in muscular vessel segments. This high basal eNOS activity in elastic vessels was also responsible for shifts of K+ concentration-contraction curves to higher external K+. VGCC-mediated contractions were similarly affected by depolarization with elevated K+ in muscular artery segments or in elastic artery segments in the absence of basal NO. However, K+-induced contractions were inhibited by the VGCC blocker diltiazem with significantly higher sensitivity in the muscular arteries, suggestive of different populations of VGCC isoforms in both vessel types. The results from the present study demonstrate that, besides passive arterial wall components, also active functional components contribute to the heterogeneity of arterial compliance along the vascular tree. This crucially facilitates the search for (patho) physiological mechanisms and potential therapeutic targets to treat or reverse large artery stiffening as occurring in aging-induced arterial stiffening.

Evaluation of Biaxial Mechanical Properties of Aortic Media Based on the Lamellar Microstructure.

Evaluation of the mechanical properties of arterial wall components is necessary for establishing a precise mechanical model applicable in various physiological and pathological conditions, such as remodeling. In this contribution, a new approach for the evaluation of the mechanical properties of aortic media accounting for the lamellar structure is proposed. We assumed aortic media to be composed of two sets of concentric layers, namely sheets of elastin (Layer I) and interstitial layers composed of mostly collagen bundles, fine elastic fibers and smooth muscle cells (Layer II). Biaxial mechanical tests were carried out on human thoracic aortic samples, and histological staining was performed to distinguish wall lamellae for determining the dimensions of the layers. A neo-Hookean strain energy function (SEF) for Layer I and a four-parameter exponential SEF for Layer II were allocated. Nonlinear regression was used to find the material parameters of the proposed microstructural model based on experimental data. The non-linear behavior of media layers confirmed the higher contribution of elastic tissue in lower strains and the gradual engagement of collagen fibers. The resulting model determines the nonlinear anisotropic behavior of aortic media through the lamellar microstructure and can be assistive in the study of wall remodeling due to alterations in lamellar structure during pathological conditions and aging.

Spectroscopic intravascular photoacoustic imaging of lipids in atherosclerosis

The natural history of atherosclerosis is marked by changes in the lipid biochemistry in the diseased arterial wall. As lesions become more vulnerable, different cholesterol species accumulate in the plaque. Understanding unstable atherosclerosis as a pharmacological and interventional therapeutic target requires chemically specific imaging of disease foci. In this study, we aim to image atherosclerotic plaque lipids and other vessel wall constituents with spectroscopic intravascular photoacoustics (sIVPA). sIVPA imaging can identify lipids in human coronary atherosclerotic plaque by relying on contrast in the near-infrared absorption spectra of the arterial wall components. Using reference spectra acquired on pure compounds, we analyzed sIVPA data from human coronary plaques ex vivo, to image plaque composition in terms of cholesterol and cholesterol ester content. In addition, we visualized the deeper lying connective tissue layers of the adventitia, as well as the fatty acid containing adipose cells in the peri-adventitial tissue. We performed simultaneous coregistered IVUS imaging to obtain complementary morphological information. Results were corroborated by histopathology. sIVPA imaging can distinguish the most prevalent lipid components of human atherosclerotic plaques and also visualize the connective tissue layers of the adventitia and the fatty acid containing adipose cells in the peri-adventitial tissue.

A novel distinctive cerebrovascular phenotype is associated with heterozygous Arg179 ACTA2 mutations

Mutations in the ACTA2 gene lead to diffuse and diverse vascular diseases; the Arg179His mutation is associated with an early onset severe phenotype due to global smooth muscle dysfunction. Cerebrovascular disease associated with ACTA2 mutations has been likened to moyamoya disease, but appears to have distinctive features. This study involved the analysis of neuroimaging of 13 patients with heterozygous missense mutations in ACTA2 disrupting Arg179. All patients had persistent ductus arteriosus and congenital mydriasis, and variable presentation of pulmonary hypertension, bladder and gastrointestinal problems associated with this mutation. Distinctive cerebrovascular features were dilatation of proximal internal carotid artery, occlusive disease of terminal internal carotid artery, an abnormally straight course of intracranial arteries, and absent basal 'moyamoya' collaterals. Patterns of brain injury supported both large and small vessel disease. Key differences from moyamoya disease were more widespread arteriopathy, the combination of arterial ectasia and stenosis and, importantly, absence of the typical basal 'moyamoya' collaterals. Evaluation of previously published cases suggests some of these features are also seen in the ACTA2 mutations disrupting Arg258. The observation that transition from dilated to normal/stenotic arterial calibre coincides with where the internal carotid artery changes from an elastic to muscular artery supports the hypothesis that abnormal smooth muscle cell proliferation caused by ACTA2 mutations is modulated by arterial wall components. Patients with persistent ductus arteriosus or congenital mydriasis with a label of 'moyamoya' should be re-evaluated to ensure the distinctive neuroimaging features of an ACTA2 mutation have not been overlooked. This diagnosis has prognostic and genetic implications, and mandates surveillance of other organ systems, in particular the aorta, to prevent life-threatening aortic dissection.

The dermatan sulfate-dependent anticoagulant pathway is mostly preserved in aneurysm and in severe atherosclerotic lesions while the heparan sulfate pathway is disrupted

BackgroundThe pathogenesis of abdominal aortic aneurysm is associated with changes of several components of arterial wall. Vascular glycosaminoglycans contribute to the non-thrombogenic activity of blood vessels. We investigated whether modifications of glycosaminoglycans in human abdominal aortic aneurysm affect their anticoagulant properties. MethodsGlycosaminoglycans were extracted from abdominal aortic aneurysms (n=11) derived from reconstitution surgeries, human abdominal aortas (n=9) from normal organ transplant donors and from preserved (n=10) and atherosclerotic (n=17) segments obtained from autopsy of an old patient. Glycosaminoglycan composition, concentration and anticoagulant activity were determined. ResultsGlycosaminoglycans extracted from aneurysms have a more potent anticoagulant activity than those from normal arteries of young adults, mostly due to a relative enrichment of dermatan sulfate, which potentiates heparin cofactor II inhibition of thrombin. Arterial segments of aged patient with severe atherosclerosis showed a glycosaminoglycan composition similar to aneurysms samples. Glycosaminoglycans extracted from these regions showed also a more potent heparin cofactor II-dependent anticoagulant activity than lesion-free areas due to the relative enrichment of dermatan sulfate. ConclusionThe anticoagulant activity from abdominal aortic aneurysms is preserved. No modifications particular to the aneurysms were dissociated from those observed in atherosclerosis.

Role of Elastic Fibers on Cardiovascular Disease

An important factor in the transition from an open to a closed circulatory system was a change in vessel wall that are dynamic structure composed of cells and extracellular matrix. The component of arterial wall in vertebrates that accounts for these properties is the elastic fiber network organized by medial smooth muscle cells. Elastin and elastin associated protein are synthesized and secreted by vascular smooth muscle cells and are the major extracellular matrix component deposited in the vascular wall. Pathological states related to hypertension or atherosclerosis is associated with vascular wall remodeling, which is deleterious for cardiovascular function. Elastic fiber may be key factors in the pathophysiology of hypertensive or atherosclerotic vascular remodeling. The well-known effects of cardiovascular disease on the deterioration and the promoted degradation of elastic fiber result to loss of arterial wall resilience. Recently, several studies have highlighted new roles for individual components of elastic fiber and their degraded products. This review describes current knowledge regarding components of elastic fibers and discusses relationship between their structural abnormalities and cardiovascular diseases.

Relationship between neointimal coverage of sirolimus-eluting stents and lesion characteristics: A study with serial coronary angioscopy

Delayed neointimal coverage after the implantation of a drug-eluting stent (DES) is thought to be related to their potential for developing late-stent thrombosis. However, few studies have shown which factor affects the neointimal coverage after DES implantation. We hypothesized that the extent of neointimal coverage after DES implantation is affected by the underlying lesion characteristics because arterial wall components are reported to determine the transport and distribution of the drugs. Thirty-seven coronary artery lesions treated with a single sirolimus-eluting stent (SES) were evaluated in 37 patients with stable coronary artery disease. Angioscopy was performed before, immediately after, and 6 months after stenting to examine the existence of yellow plaque, thrombus, complex plaque, and intramural hemorrhage and the degree of neointimal coverage at 6-month follow-up. This was classified either as a noncoverage group (stent struts were predominantly exposed or visible through a thin neointima) or as a coverage group (stent struts were predominantly covered by neointimal hyperplasia and thus invisible). Twenty-one lesions were classified into the noncoverage group, and 16 lesions the coverage group. The frequency of preexistent yellow plaques was significantly higher in the noncoverage group than that in the coverage group (67% vs 19%, P = .007). A multivariate logistic regression analysis showed the preexistence of yellow plaque was the only independent factor behind less neointimal coverage at 6 months after SES implantation (odds ratio 19.5, 95% confidence interval 1.58-240.50, P = .020). The preexistence of yellow plaque may be associated with decreased neointimal coverage of SES.

Anti-Inflammatory Drugs and Statins for Arterial Stiffness Reduction

Arterial stiffness is a powerful predictor of cardiovascular outcome in various patient groups as well as in general population, and can directly accelerate the atherosclerotic process. Arterial stiffness is regulated by numerous factors. Traditionally, mean arterial pressure and structural changes in the components of arterial wall were thought to be main determinants of arterial stiffness, however it is now recognized that arterial stiffness is also regulated by the smooth muscle tone and that endothelium derived mediators, such as NO, contribute to the functional regulation of arterial stiffness. It has also become apparent that inflammation has an important role in the stiffening of the large arteries, possibly via changes in the composition of the arterial wall due to inflammatory cell infiltration or via endothelial dysfunction. Recently, numerous small scale interventional studies have looked into the possibility of using anti-inflammatory and cholesterol-reduction therapies with anti-inflammatory properties as a means to reduce arterial stiffness and therefore cardiovascular risk. Anti-inflammatory therapies, such as corticosteroids and anti-TNF alpha therapy have been shown to reduce arterial stiffness in patients with chronic inflammatory conditions. In addition, statins and other cholesterol-reducing agents have been shown to have beneficial effects on wave reflection and aortic stiffness reduction in several patient groups. This review aims to explore the studies investigating the role of inflammation on arterial stiffening and to review the results from the studies investigating the effect of anti-inflammatory drugs and statins for arterial stiffness reduction and finally, to discuss the potential mechanisms by which these drugs may reduce arterial stiffness.