Vessel Wall Components Research Articles

Motion Contrast, Phase Gradient, and Simultaneous OCT Images Assist in the Interpretation of Dark-Field Images in Eyes with Retinal Pathology.

The cellular-level visualization of retinal microstructures such as blood vessel wall components, not available with other imaging modalities, is provided with unprecedented details by dark-field imaging configurations; however, the interpretation of such images alone is sometimes difficult since multiple structural disturbances may be present in the same time. Particularly in eyes with retinal pathology, microstructures may appear in high-resolution retinal images with a wide range of sizes, sharpnesses, and brightnesses. In this paper we show that motion contrast and phase gradient imaging modalities, as well as the simultaneous acquisition of depth-resolved optical coherence tomography (OCT) images, provide additional insight to help understand the retinal neural and vascular structures seen in dark-field images and may enable improved diagnostic and treatment plans.

Extracellular matrix molecules associated with lymphatic vessels in health and disease.

Lymphatic vessels (LyVs), responsible for fluid, solute, and immune cell homeostasis in the body, are closely associated with the adjacent extracellular matrix (ECM) molecules whose structural and functional impact on LyVs is currently more appreciated, albeit not entirely elucidated. These molecules, serving as a platform for various connective tissue cell activities and affecting LyV biology should be considered also as an integral part of the lymphatic system. Any alterations and changes in ECM molecules over the course of disease impair the function and structure of the LyV network. Remodeling of LyV cells, which are components of lymphatic vessel walls, also triggers alterations in ECM molecules and interstitial tissue composition. Therefore, in this review we aimed to present the current knowledge on ECM in tissues and particularly on molecules surrounding lymphatics in normal conditions and in disease.

Phosphotungstic acid (PTA) preferentially binds to collagen- rich regions of porcine carotid arteries and human atherosclerotic plaques observed using contrast enhanced micro-computed tomography (CE-µCT).

Background and aims: Atherosclerotic plaque rupture in the carotid artery can cause small emboli to travel to cerebral arteries, causing blockages and preventing blood flow leading to stroke. Contrast enhanced micro computed tomography (CEμCT) using a novel stain, phosphotungstic acid (PTA) can provide insights into the microstructure of the vessel wall and atherosclerotic plaque, and hence their likelihood to rupture. Furthermore, it has been suggested that collagen content and orientation can be related to mechanical integrity. This study aims to build on existing literature and establish a robust and reproducible staining and imaging technique to non-destructively quantify the collagen content within arteries and plaques as an alternative to routine histology. Methods: Porcine carotid arteries and human atherosclerotic plaques were stained with a concentration of 1% PTA staining solution and imaged using MicroCT to establish the in situ architecture of the tissue and measure collagen content. A histological assessment of the collagen content was also performed from picrosirius red (PSR) staining. Results: PTA stained arterial samples highlight the reproducibility of the PTA staining and MicroCT imaging technique used with a quantitative analysis showing a positive correlation between the collagen content measured from CEμCT and histology. Furthermore, collagen-rich areas can be clearly visualised in both the vessel wall and atherosclerotic plaque. 3D reconstruction was also performed showing that different layers of the vessel wall and various atherosclerotic plaque components can be differentiated using Hounsfield Unit (HU) values. Conclusion: The work presented here is unique as it offers a quantitative method of segmenting the vessel wall into its individual components and non-destructively quantifying the collagen content within these tissues, whilst also delivering a visual representation of the fibrous structure using a single contrast agent.

Neutrophil extracellular traps accelerate vascular smooth muscle cell proliferation via Akt/CDKN1b/TK1 accompanying with the occurrence of hypertension.

Objective:Neutrophil extracellular traps (NETs) can trigger pathological changes in vascular cells or vessel wall components, which are vascular pathological changes of hypertension. Therefore, we hypothesized that NETs would be associated with the occurrence of hypertension.Methods:To evaluate the relationship between NETs and hypertension, we evaluated both the NETs formation in spontaneously hypertensive rats (SHRs) and the blood pressure of mice injected phorbol-12-myristate-13-acetate (PMA) via the tail vein to induce NETs formation in arterial wall. Meanwhile, proliferation and cell cycle of vascular smooth muscle cells (VSMCs), which were co-cultured with NETs were assessed. In addition, the role of exosomes from VSMCs co-cultured with NETs on proliferation signaling delivery was assessed.Results:Formation of NETs increased in the arteries of SHR. PMA resulted in up-regulation expression of citrullinated Histone H3 (cit Histone H3, a NETs marker) in the arteries of mice accompanied with increasing of blood pressure. NET treatment significantly increased VSMCs count and accelerated G1/S transition in vitro. Cyclin-dependent kinase inhibitor 1b (CDKN1b) was down-regulated and Thymidine kinase 1 (TK1) was up-regulated in VSMCs. Exosomes from VSMCs co-cultured with NETs significantly accelerated the proliferation of VSMCs. TK1 was up-regulated in the exosomes from VSMCs co-cultured with NETs and in both the arterial wall and serum of mice with PMA.Conclusion:NETs promote VSMCs proliferation via Akt/CDKN1b/TK1 and is related to hypertension development. Exosomes from VSMCs co-cultured with NETs participate in transferring the proliferation signal. These results support the role of NETs in the development of hypertension.

Matrix recruitment by malignant cells (MRMC) in uterine serous carcinoma (USC)-derived ARK1 identifies the procurement of vessel wall components (VWCs) as novel therapeutic target

<h3>Objectives:</h3> USC and its ovarian counterpart (OSC), the most lethal gynecologic malignancies, are resistant to current therapies. We noted that the highly annotated USC-derived cell line ARK1 lacks expression of collagen type III (COL3), the master organizer of VWC deposition during angiogenesis as evidenced by the COL3-deficient vascular Ehlers-Danlos Syndrome (OMIM 130050). In USC, vascular COL3 may therefore originate from interstitial cells via MRMC. We hypothesized ARK1 to express mediators of MRMC. Our objective was to test this hypothesis in standard culture (SC) and in angiogenic overdrive (AO) condition, using both gene expression profiles for anti-cancer drug discovery. Our AO protocol employs FDA-approved medicines that maximally push <i>and</i> maximally brake angiogenesis by inhibiting ketoglutarate-utilizing protein hydroxylases (KPHs), e.g. the enzymes forming peptide-bound hydroxylproline. We reported that such medicines advance angiogenesis via activated molecular oxygen sensing <i>yet at the same time</i> inhibit deposition of the stable collagenous matrix required for angiogenesis, thus trapping cancer cells between ‘hammer and anvil'. <h3>Methods:</h3> Cell culture, repeat RNA-seq, antigen-specific protein detection. <h3>Results:</h3> ARK1-SC expressed an extraordinary array of angiogenesis-relevant genes that encode a) the mediators of MRMC (connective tissue growth factor [CTGF], the suite of fibroblast growth factors [FGFs, FGFR1-4, FGFRL1, FRS2-3, FGFBP1] and ligands signaling over a few cell diameters [e.g. WNT5B]; b) all elemental VWCs except COL3 (49 collagen/laminin/fibrillin chains; the entire elastin suite [ELN, LOX, LOXL1-4, EMILIN1-3, MMRN2, FBLN5] and proteoglycans [e.g. HSPG2, VCAN]; c) angiogenic factors, from capillary tube formation to branching morphology (e.g. all 6 subunits of the hypoxia inducible factors [HIF1-3]; the suite of vascular endothelial growth factors [VEGFA-C, FIGF, FLT1, KDR, FLT4]; NRP1; HBEGF; even the beta-2 adrenergic receptor ADRB2]; d) the complete set of 41 KPHs required for physiological function in a-c. After 48 hours at clinical concentrations of the KPH-inhibitory medicine deferiprone, ARK1-AO accumulated underhydroxylated collagens intracellularly, indicating blockade of collagen secretion due to triple helix collapse and mis-folding. Simultaneously, expression of CTGF increased 16.1-fold, FGF2 2.5-fold, FGF1 14.5-fold, and FGF5 23.8-fold over control ARK1-SC (RPKM-based FDR p: 10^-2 to 10^-6) whereas expression of their corresponding receptors remained unchanged and COL3 expression defective. VEGFA/VEGFB expression fell by almost 50%, with likewise unchanged receptor expression. HBEGF expression rose 9-fold (FDR p<10^-6), suggesting it to be the major angiogenic mediator of MRMC. Further indicating self-contradictory signaling conflict induced by KPH inhibition, expression of WNT5B rose 5.5-fold, yet of its antagonist DKK1 46-fold (FDR p=10^-5). <h3>Conclusions:</h3> ARK1 is a genetically defined USC model to interrogate the targeted disruption of MRMC. The pioneer KPH inhibitory medicine deferiprone exploits the asymmetry between KPH-stabilized matrix proteins (e.g. collagens) and KPH-destabilized oxygen sensors (e.g. HIFs) to disrupt both and in this process, reveal the genetic circuitry for matrix recruitment and angiogenesis. We identify CTGF, FGFs, and HBEGF as key factors that enroll interstitial cells for procurement of tumor perfusion. We anticipate therapeutic value of current CTGF/FGFs/HBEGF antagonists in USC (and OSC).

Stiffness of Vascular Smooth Muscle Cells from Monkeys Studied using Atomic Force Microscopy

Vascular smooth muscle cells (VSMC) are the main cellular components of blood vessel walls and bear external mechanical forces caused by blood flow and pressure. In this report, we have verified the following hypothesis through experiments: The increase in VSMC stiffness may be mainly due to changes in vascular stiffness due to aging. Although aging enhances the stiffness and adhesion of VSMC, there is no significant difference in apparent elastic modulus and adhesion between the VSMC obtained by male and female. The effect of aging through the ECM-integrin-cytoskeleton axis is related to increased VSMC stiffness and matrix adhesion rather than gender.

Exercise Improves Endothelial Function Associated with Alleviated Inflammation and Oxidative Stress of Perivascular Adipose Tissue in Type 2 Diabetic Mice.

Perivascular adipose tissue (PVAT), a type of adipose tissue that surrounds the blood vessels, has been considered an active component of the blood vessel walls and involved in vascular homeostasis. Recent evidence shows that increased inflammation and oxidative stress in PVAT contribute to endothelial dysfunction in type 2 diabetes (T2D). Exercise is an important nonpharmacological approach for vascular diseases. However, there is limited information regarding whether the beneficial effects of exercise on vascular function is related to the PVAT status. In this study, we investigated whether exercise can decrease oxidative stress and inflammation of PVAT and promote the improvement of endothelial function in a T2D mouse model. Diabetic db/db (5-week old) mice performed treadmill exercise (10 m/min) or keep sedentary for 8 weeks. Body weight, fasting blood glucose levels, glucose, and insulin tolerance were determined. The cytokines (IL-6, IL-10, IFN-γ, and TNF-a) and adiponectin levels, macrophage polarization and adipocyte type in PVAT, oxidative stress, and nitric oxide (NO) expression in the vascular wall were evaluated. The adhesion ability of primary aorta endothelial cells was analyzed. Our data showed that (1) diabetic db/db mice had increased body weight and fasting blood glucose level, compromised glucose tolerance, and insulin sensitivity, which were decreased/improved by exercise intervention. (2) Exercise intervention increased the percentage of multilocular brown adipocytes, promoted M1 to M2 macrophage polarization, associating with an increase of adiponectin and IL-10 levels and decrease of IFN-γ, IL-6, and TNF-a levels in PVAT. (3) Exercise decreased superoxide production in PVAT and the vascular wall of diabetic mice, accompanied with increased NO level. (4) The adhesion ability of aorta endothelial cells to leukocytes was decreased in exercised db/db mice, accompanied by decreased intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) expressions. Of interesting, coculture with PVAT-culture medium from exercised db/db mice could also reduce ICAM-1 and VCAM-1 expressions in primary endothelial cells. In conclusion, our data suggest that exercise improved endothelial function by attenuating the inflammation and oxidative stress in PVAT.

Contribution of perivascular adipose tissue to vascular dysfunction in obesity

Background and Aims: Perivascular adipose tissue (PVAT) has emerged as an active component of the blood vessel wall regulating vascular homeostasis. The main goal of this study was to investigate the effects of high-fat diet on PVAT and study its impact on endothelial function of mesenteric arteries of obese animal models.

Intravascular ultrasound guidance in the evaluation and treatment of left main coronary artery disease

Percutaneous coronary intervention (PCI) of left main coronary artery (LMCA) disease has become an acceptable revascularization strategy. Evaluating the extent and characteristics of obstructive disease of the LMCA by angiography is challenging and limited in its accuracy. In contrast, intravascular ultrasound (IVUS) provides accurate imaging of the coronary lumen as well as quantitative measurements and quantitative assessment of the vessel wall components. IVUS for LMCA PCI should be performed before, during, and after intervention; IVUS enhances every step in the procedure and is associated with a mortality advantage in comparison with angiographic guidance alone. In this review, we provide an update on LMCA PCI and the role of IVUS for lesion assessment and stent optimization. In addition, the latest clinical evidence of the benefits of IVUS-guided LMCA PCI as compared to angiography is reviewed.

Pleiotropic actions of factor Xa inhibition in cardiovascular prevention: mechanistic insights and implications for anti-thrombotic treatment.

Atherosclerosis is a chronic inflammatory disease in which atherothrombotic complications lead to cardiovascular morbidity and mortality. At advanced stages, myocardial infarction, ischaemic stroke, and peripheral artery disease, including major adverse limb events, are caused either by acute occlusive atherothrombosis or by thromboembolism. Endothelial dysfunction, vascular smooth muscle cell activation, and vascular inflammation are essential in the development of acute cardiovascular events. Effects of the coagulation system on vascular biology extend beyond thrombosis. Under physiological conditions, coagulation proteases in blood are pivotal in maintaining haemostasis and vascular integrity. Under pathological conditions, including atherosclerosis, the same coagulation proteases (including factor Xa, factor VIIa, and thrombin) become drivers of atherothrombosis, working in concert with platelets and vessel wall components. While initially atherothrombosis was attributed primarily to platelets, recent advances indicate the critical role of fibrin clot and plasma coagulation factors. Mechanisms of atherothrombosis and hypercoagulability vary depending on plaque erosion or plaque rupture. In addition to contributing to thrombus formation, factor Xa and thrombin can affect endothelial dysfunction, oxidative stress, vascular smooth muscle cell function as well as immune cell activation and vascular inflammation. By these mechanisms, they promote atherosclerosis and contribute to plaque instability. In this review, we first discuss the postulated vasoprotective mechanisms of protease-activated receptor signalling induced by coagulation enzymes under physiological conditions. Next, we discuss preclinical studies linking coagulation with endothelial cell dysfunction, thromboinflammation, and atherogenesis. Understanding these mechanisms is pivotal for the introduction of novel strategies in cardiovascular prevention and therapy. We therefore translate these findings to clinical studies of direct oral anticoagulant drugs and discuss the potential relevance of dual pathway inhibition for atherothrombosis prevention and vascular protection.

46-LB: Exercise Improves Endothelial Function Associated with Alleviated Inflammation and Oxidative Stress of Perivascular Adipose Tissue in Type 2 Diabetic Mice

Perivascular adipose tissue (PVAT), a type of adipose tissue which surrounds blood vessels, has been considered as an active component of blood vessel walls and involved in vascular homeostasis. Recent evidence shows that increased inflammation and oxidative stress in PVAT contribute to endothelial dysfunction in type 2 diabetes (T2D). Exercise is an important non-pharmacological approach for vascular diseases. However, there is limited information regarding whether the beneficial effects of exercise on vascular function is related to PVAT status. In this study, we investigated whether exercise can decrease oxidative stress and inflammation of PVAT and promote the improvement of endothelial function in a T2D mouse model. Diabetic db/db (5-wk old) mice performed treadmill exercise (10 m/min) or keep sedentary for 8 wks. Body weight, fasting blood glucose levels, glucose and insulin tolerance were determined. The cytokines (IL-6, IL-10, IFN-r, TNF-a) and adiponectin levels, macrophage polarization in PVAT, and oxidative stress and nitric oxide expression in vascular wall were evaluated. The leukocyte adhesion ability of aorta endothelial cells isolated from the db/db mice was analyzed. Our data showed that: 1) Exercise decreased body weight and the fasting blood glucose level as well as improved glucose tolerance and insulin sensitivity in T2D mice. 2) Exercise increased adiponectin and IL-10 levels, decreased IFN-r, IL-6, TNF-a levels and promoted M1 to M2 polarization in PVAT. 3) Exercise decreased superoxide production in the vascular wall of diabetic mice, accompanied with increased nitric oxide bioavailability. 4) Exercise decreased the adhesion of diabetic aorta endothelial cells to leukocytes, accompanying with decreased ICAM-1 and VCAM-1 expression. In conclusion, our data suggest that exercise improved endothelial function by attenuating the oxidative stress and inflammation in PVAT. Disclosure J. Wang: None. V. Polaki: None. S. Chen: None. J. Bihl: None. Funding American Diabetes Association (1-17-IBS-187 to J.B.)

Epulises: current problem

Relevance. Nowadays an important problem in dentistry is the early diagnosis and the treatment of tumors and tumor-like lesions. One of the most frequent lesions of the orofacial region, and particularly of the periodontium, is a non-tumor lesion called epulis. Some tumors and tumor-like lesions may be both clinically and histologically similar, hence the diagnosis and the differential diagnosis of the epulis is still complicated and need to pay attention. Moreover, every type of epulis has particular histological features that make a clinician use a specific treatment in each clinical case. The treatment success and the necessity of the further observations are determined by the correct diagnosis. However, there is still controversial data about epulis diagnosis. Moreover, the reliable criteria for correct diagnosis of each type of epulis have not been discussed yet.Purpose. The aim of this study is to determine the most relevant methods for differential diagnosis of every type of epulis and other tumor and tumor-like lesions of the alveolar ridge with the same clinical and histological descriptions was performed.Materials and methods. In this article the review of the literature is presented. A comprehensive literature search of the studies from 1970 through 2019 in PubMed database regarding the epulis and other tumor and tumor-like lesions with the same clinical and histological descriptions was performed. 71 relevant articles were selected.Results. “Epulis” is a term that refers to tumor and tumor-like lesions of the alveolar ridge. Due to their morphological features it is frequently necessary to carry out not only the histological studies but also use immunohistochemical and genetic analyses. It is not complicated to verify vascular epulis and fibrous epulis. If there is a plasma-cell infiltration of fibrous epulis stroma, clinician is to differ it from IgG4-assosiated diseases. In some cases to discern pyogenic granuloma and hemangioma it is necessary to carry out immunohistochemical study of the blood vessel wall components. It is also important to know diagnostics of giant-cell epulis. Here to divide peripheral and central giant-cell granulomas genetic analysis should be carried out.Conclusion. Usually microscopic study of fibrous and vascular epulis helps to differentiate it with other lesions. The IgG4associated diseases are to exclude by immunohistochemical study. Diagnostics of giant-cell epulis may include both immunochemical and genetic studies. Methods presented in this article are important both for treatment and for prognosis of the disease.

A post-market, multi-vessel evaluation of the imaging of peripheral arteries for diagnostic purposeS comparing optical Coherence tomogrApy and iNtravascular ultrasound imaging (SCAN)

BackgroundIntravascular imaging plays an important part in diagnosis of vascular conditions and providing insight for treatment strategy. Two main imaging modalities are intravascular ultrasound (IVUS) and optical coherence tomography (OCT). The objective of this study was to prove non-inferiority of OCT imaging to IVUS images in matched segments of peripheral vessels in patients with suspected peripheral vascular disease.MethodsThe SCAN study was a prospective, non-inferiority clinical study of matched IVUS and OCT images collected along defined segments of peripheral vessels from twelve subjects (mean age 68 ± 10.3 years; 10 men) displaying symptoms of vascular disease. Luminal diameters were measured by both imaging systems at the distal, middle, and proximal points of the defined segments. Three blinded interventional radiologists evaluated the quality of both imaging modalities in identifying layered structures (3-point grading), plaque (5-point grading), calcification (5-point grading), stent structure (3-point grading), and artifacts (3-point grading) from 240 randomly ordered images. Mean grading scores and luminal diameters were calculated and analyzed with Student’s t-Test and Mann-Whitney-Wilcoxon testing. Intrareader reproducibility was calculated by intraclass correlation (ICC) analysis.ResultsThe mean scoring of plaque, calcification, and vascular stent struts by the three readers was significant better in terms of image quality for OCT than IVUS (p < 0.001, p = 0.001, p = 0.004, respectively). The mean scores of vessel wall component visibility and artifacts generated by the two imaging systems were not significantly different (p = 0.19, p = 0.07, respectively). Mean vessel luminal diameter and area at three specific locations within the vessels were not significantly different between the two imaging modalities. No patient injury, adverse effect or device malfunction were noted during the study.ConclusionsImaging by OCT provides the physician with better visualization of some vessel and plaque chacteristics, but both IVUS and OCT imaging are safe and effective methods of examining peripheral vessels in order to perform diagnostic assessment of peripheral vessels and provide information necessary for the treatment strategy of peripheral artery disease.Trial registrationNCT03480685 registered on 29 March 2018.

Autophagy regulates the function of vascular smooth muscle cells in the formation and rupture of intracranial aneurysms

Vascular smooth muscle cells (VSMC) are the main cellular component of vessel wall. The changes of VSMC functions including phenotypic transformation and apoptosis play a critical role in the pathogenesis of intracranial aneurysm (IA). Autophagy can participate in the regulation of vascular function by regulating cell function. In the initial stage of IA, the activation of autophagy can accelerate the phenotypic transformation of VSMC and inhibit VSMC apoptosis. With the progress of IA, the relationship between autophagy and apoptosis changes from antagonism to synergy or promotion, and a large number of apoptotic VSMC lead to the rupture of IA. In this review, we describe the role of autophagy regulating the function of VSMC in the occurrence, development and rupture of IA, for further understanding the pathogenesis of IA and finding molecular targets to prevent the formation and rupture of IA.

Promoters to Study Vascular Smooth Muscle.

Smooth muscle cells (SMCs) are a critical component of blood vessel walls that provide structural support, regulate vascular tone, and allow for vascular remodeling. These cells also exhibit a remarkable plasticity that contributes to vascular growth and repair but also to cardiovascular pathologies, including atherosclerosis, intimal hyperplasia and restenosis, aneurysm, and transplant vasculopathy. Mouse models have been an important tool for the study of SMC functions. The development of smooth muscle-expressing Cre-driver lines has allowed for exciting discoveries, including recent advances revealing the diversity of phenotypes derived from mature SMC transdifferentiation in vivo using inducible CreER T2 lines. We review SMC-targeting Cre lines driven by the Myh11, Tagln, and Acta2 promoters, including important technical considerations associated with these models. Limitations that can complicate study of the vasculature include expression in visceral SMCs leading to confounding phenotypes, and expression in multiple nonsmooth muscle cell types, such as Acta2-Cre expression in myofibroblasts. Notably, the frequently employed Tagln/ SM22α- Cre driver expresses in the embryonic heart but can also confer expression in nonmuscular cells including perivascular adipocytes and their precursors, myeloid cells, and platelets, with important implications for interpretation of cardiovascular phenotypes. With new Cre-driver lines under development and the increasing use of fate mapping methods, we are entering an exciting new era in SMC research.

The cofilin phosphatase slingshot homolog 1 restrains angiotensin II-induced vascular hypertrophy and fibrosis in vivo

The dual specificity phosphatase slingshot homolog 1 (SSH1) contributes to actin remodeling by dephosphorylating and activating the actin-severing protein cofilin. The reorganization of the actin cytoskeleton has been implicated in chronic hypertension and the subsequent mechano-adaptive rearrangement of vessel wall components. Therefore, using a novel Ssh1−/− mouse model, we investigated the potential role of SSH1 in angiotensin II (Ang II)-induced hypertension, and vascular remodeling. We found that loss of SSH1 did not produce overt phenotypic changes and that baseline blood pressures as well as heart rates were comparable between Ssh1+/+ and Ssh1−/− mice. Although 14 days of Ang II treatment equally increased systolic blood pressure in both genotypes, histological assessment of aortic samples indicated that medial thickening was exacerbated by the loss of SSH1. Consequently, reverse-transcription quantitative PCR analysis of the transcripts from Ang II-infused animals confirmed increased aortic expression levels of fibronectin, and osteopontin in Ssh1−/− when compared to wild-type mice. Mechanistically, our data suggest that fibrosis in SSH1-deficient mice occurs by a process that involves aberrant responses to Ang II-induced TGFβ1. Taken together, our work indicates that Ang II-dependent fibrotic gene expression and vascular remodeling, but not the Ang II-induced pressor response, are modulated by SSH1-mediated signaling pathways and SSH1 activity is protective against Ang II-induced remodeling in the vasculature.

Quantitative CT assessment identifies more heart transplanted patients with progressive coronary wall thickening than standard clinical read

BackgroundWe sought to compare quantitative coronary CT angiography (CTA) assessment versus standard clinical reading to identify heart transplanted (HTX) patients with progressive coronary wall thickening. Methods35 patients (23 males, age 58 [IQR: 50;61] years) underwent 256-slice coronary CTA at one year and two years after HTX to rule out cardiac allograft vasculopathy (CAV). In addition to the standard clinical read, we quantified total vessel wall volume in all coronaries up to 2-mm luminal diameter. Fixed threshold settings were used to assess calcified (>350 HU) and non-calcified vessel wall components with high- (131–350 HU), intermediate- (75–130 HU) and low-attenuation (<75 HU). ResultsTotal lumen volume did not change between baseline and follow-up studies (p = 0.59). Total vessel wall volume showed significant increase (464 [IQR: 338; 570] vs. 563 [IQR: 345; 717] mm3, p < 0.001). The volume of high-, intermediate and low-attenuation non-calcified wall components showed progression (332 [IQR: 217;425] vs. 385 [IQR: 238;489], 40 [IQR: 12;48] vs. 59 [IQR: 16;83] and 18 [IQR: 4;21] vs. 46 [IQR: 6;41] mm3, respectively, p < 0.05 all), while calcified volume did not change between baseline and follow-up CTAs (72 [IQR: 16;127] vs. 72 [IQR: 29;102] mm3, p = 0.73). Quantitative analysis identified more patients with progressive coronary wall thickening (≥10% cut-off) than standard clinical read (11 vs. 22, p = 0.01). ConclusionQuantitative coronary wall assessment is feasible with coronary CTA in HTX patients. Coronary wall thickening within the first two years after HTX is mainly attributable to non-calcified lesion components and might be an early sign of CAV.

Blood flow patterns and pressure loss in the ascending aorta: A comparative study on physiological and aneurysmal conditions

An aortic aneurysm is defined as a balloon-shaped bulging of all three histologic components of the aortic vessel walls (intima, media and adventitia). This dilation results from vessel weakening owing to remodeling, i.e. due to cystic degeneration of the Tunica media (Marfan), progression of atherosclerosis or presence of a bicuspid aortic valve. The growth rate of the aortic diameter varies from patient to patient and may progress until the aneurysm ultimately ruptures. The role of hemodynamics, i.e. blood flow patterns, and shear stresses that are supposed to intensify during aneurysm growth are not yet fully understood, but thought to play a key role in the enlargement process. The aim of this study is to characterize the aortic blood flow in a silicone model of a pathological aorta with ascending aneurysm, to analyze the differences in the blood flow pattern compared to a healthy aortic model, and to single out possible blood flow characteristics measurable using phase contrast magnetic resonance imaging (MRI) that could serve as indicators for aneurysm severity. MRI simulations were performed under physiological, pulsatile flow conditions using data obtained from optical three dimensional particle tracking measurements. In comparison to the healthy geometry, elevated turbulence intensity and pressure loss are measured in the diseased aorta, which we propose as a complimentary indicator for assessing the aneurysmal severity. Our results shed a light on the interplay between the blood flow dynamics and their contribution to the pathophysiology and possible role for future risk assessment of ascending aortic aneurysms.

Sinusoidal hemangioma and intravascular papillary endothelial hyperplasia: Interrelated processes that share a histogenetic piecemeal angiogenic mechanism

Sinusoidal hemangioma, characterized by interconnecting thin-walled vascular spaces, may present papillae/pseudo-papillae and zones that resemble intravascular papillary endothelial hyperplasia (IPEH). Our objectives are to explore the existence of zones in IPEH with sinusoidal hemangioma characteristics, the mechanism of papillary and septa formation in sinusoidal hemangioma and the comparison of this mechanism with that in IPEH. For these purposes, specimens of 4 cases of each entity were selected and studied by serial histologic sections and by immunochemistry and immunofluorescence procedures. The results showed a) zones with characteristics of sinusoidal hemangioma in IPEH cases, b) presence in both entities of papillae with a cover formed by a monolayer of CD34+ and CD31+ endothelial cells (ECs) and a core formed by either type I collagen and αSMA+ cells (presenting a pericyte/smooth muscle cell aspect) or thrombotic components, and c) a similar piecemeal angiogenic mechanism in papillary formation, including sprouting of intimal ECs toward the vessel wall itself or intravascular thrombi, formation of vascular loops that encircle and separate vessel wall or thrombus components, and parietal or thrombotic papillae development. The major differences between both entities were the number, arrangement and substrate of papillae: myriad, densely grouped, parietal and thrombotic papillae in IPEH, and a linear arrangement of predominant parietal papillae in sinusoidal hemangioma, originating septa (segmentation). In conclusion, sinusoidal hemangioma and IPEH are interrelated processes, which share morphologic findings and a piecemeal angiogenic mechanism, combining sprouting and intussusceptive angiogenesis, and leading to papillary formation and vessel segmentation.

The effects of membrane cholesterol on the mechanics of vascular smooth muscle cell

As the major cellular component of blood vessel wall, vascular smooth muscle cell (VSMC) plays important roles at each stage of atherosclerosis by proliferation and migration toward the inner layer of blood vessel wall. It is also known that cholesterol is not only the major factor involved in fatty deposition in the atherosclerotic lesion, but also plays an important role as a regulator of cell mechanics, spreading, and migration. A further complication is the mechanical environment of the vascular wall, which undergoes progressive stiffening with aging and hypertension and thus accelerates development of atherosclerosis. Therefore, it is important to investigate the combined effect of cholesterol and mechanical environment on VSMC and determine how it alters VSMC functional characteristics such as cell stiffness and adhesion. VSMCs used in this study were enzymatically isolated from the descending aorta of male Sprague‐Dawley rats and cultured in DMEM with 10% FBS in a humidified incubator at 37°C and 5% CO2. Cell adhesion was measured for 50–70% confluent cells with an atomic force microscope (AFM) system and the fibronectin (FN) or N‐cadherin coated stylus AFM probes at 100 nm/sec retraction speed. Cell stiffness was tested with spherical AFM probe (5μm diameter) at 1 μm/sec indentation speed. Cells were treated with 5mM Methyl‐β‐cyclodextrin for 1 h for cholesterol depletion prior to the AFM experiment. Our results showed that cholesterol depletion significantly increased N‐cadherin mediated cell adhesion by ~20% and adhesion probability by ~35%, respectively. While α5β1/FN adhesion force significantly decreased upon membrane cholesterol depletion. Moreover, our results suggested that cholesterol depletion significantly reduced VSMCs stiffness by 47% compared to control cells. All together, these results reveal that membrane cholesterol is a key regulator for cellular stiffness and integrin/cadherin‐mediated cell adhesion. The knowledge that we obtained in this project may lead to a novel therapeutic strategy that could potentially control and block VSMC migration and prevent the formation of atherosclerotic plaque by regulating integrin and/or cadherin mediated cell adhesion.Support or Funding Information15SDG25420001 (AHA)