ABSTRACT
BACKGROUND: The success rate of percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) is lower and the risk for complications higher compared with other non-CTO PCI. Although interventionalists focus on intimal plaque characteristics, the coronary media is an important (especially for techniques involving antegrade dissection and re-entry) but poorly understood structure in CTO PCI. OBJECTIVES: The aim of the present study was to investigate coronary medial wall thinning in CTO lesions and determine how this thinning might affect CTO PCI. METHODS: A total of 2,586 sections were investigated, from arteries with evidence of CTO from 54 subjects (1,383 sections) and arteries without evidence of CTO from 54 subjects with non-coronary-related deaths (1,203 sections) after matching for age, gender, body weight, and body height. RESULTS: The medial thickness in subjects with CTO was lower than that in those with non-coronary-related death (P < 0.001). In subjects with CTO, CTO lesions had thinner medial walls compared with those with lower luminal narrowing (P < 0.001). At the CTO distal segments, the 6- to 12-mm distal segment from the distal end of the CTO had significantly less luminal narrowing (P < 0.001), and similar medial thickness, compared with the distal end of the CTO. Immunohistochemical analysis revealed that short-duration CTO had more cleaved caspase-3-positive cells in media and had significantly more CD3+, CD4+, CD8+, and CD4+CD28null T cells compared with long-duration CTO. CONCLUSIONS: CTO lesions demonstrated coronary medial thinning compared with non-CTO lesions. Further investigation of the cause-and-effect relationship among inflammation, apoptosis, and coronary medial wall thinning is warranted in future mechanistic studies.
Subject(s)
Coronary Occlusion , Coronary Vessels , Percutaneous Coronary Intervention , Humans , Coronary Occlusion/diagnostic imaging , Coronary Occlusion/pathology , Male , Female , Middle Aged , Aged , Chronic Disease , Percutaneous Coronary Intervention/adverse effects , Percutaneous Coronary Intervention/instrumentation , Coronary Vessels/diagnostic imaging , Coronary Vessels/pathology , Risk Factors , Treatment Outcome , Apoptosis , Vascular Remodeling , Tunica Media/pathology , Tunica Media/diagnostic imaging , Case-Control Studies , Coronary AngiographyABSTRACT
BACKGROUNDDisease of the aorta varies from atherosclerosis to aneurysms, with complications including rupture, dissection, and poorly characterized limited tears. We studied limited tears without any mural hematoma, termed intimomedial tears, to gain insight into aortic vulnerability to excessive wall stresses. Our premise is that minimal injuries in aortas with sufficient medial resilience to prevent tear progression correspond to initial mechanisms leading to complete structural failure in aortas with significantly compromised medial resilience.METHODSIntimomedial tears were macroscopically identified in 9 of 108 ascending aortas after surgery and analyzed by histology and immunofluorescence confocal microscopy.RESULTSNonhemorrhagic, nonatheromatous tears correlated with advanced aneurysmal disease and most lacked distinctive symptoms or radiological signs. Tears traversed the intima and part of the subjacent media, while the resultant defects were partially or completely filled with neointima characterized by differentiated smooth muscle cells, scattered leukocytes, dense fibrosis, and absent elastic laminae despite tropoelastin synthesis. Healed lesions contained organized fibrin at tear edges without evidence of plasma and erythrocyte extravasation or lipid accumulation.CONCLUSIONThese findings suggest a multiphasic model of aortic wall failure in which primary lesions of intimomedial tears either heal if the media is sufficiently resilient or progress as dissection or rupture by medial delamination and tear completion, respectively. Moreover, mural incorporation of thrombus and cellular responses to injury, two historically important concepts in atheroma pathogenesis, contribute to vessel wall repair with adequate conduit function, but even together are not sufficient to induce atherosclerosis.FUNDINGNIH (R01-HL146723, R01-HL168473) and Yale Department of Surgery.
Subject(s)
Aorta , Atherosclerosis , Fibrosis , Myocytes, Smooth Muscle , Humans , Male , Myocytes, Smooth Muscle/pathology , Myocytes, Smooth Muscle/metabolism , Atherosclerosis/pathology , Female , Aorta/pathology , Aged , Middle Aged , Neointima/pathology , Tunica Intima/pathology , Tunica Media/pathology , Tunica Media/metabolismABSTRACT
BACKGROUND: Sclerotherapy is a cornerstone of the treatment of chronic venous disease, despite some technical aspects (e.g., sclerosant liquid agent concentration [SLAC] and contact time between sclerosant agent and vein wall [ctSA/VW]) to maximize outcomes remain an unsolved problem and a source of debate. An innovative three-balloon catheter has been developed to allow sclerotherapy in empty vein conditions (Empty Vein Ablation technique, EVA), revolutionizing the definition of SLAC and ctSA/VW. Aim of this experimental study is to analyze EVA effects on intima and media vessel tunicae using different SLAC and ctSA/VW in an in-vivo animal model. METHODS: Two adult sheep were treated by EVA using jugular and common iliac vein axes (eight vein segments). Different SLAC (polidocanol 0.5% or 1%) and different ctSA/VW (3 or 5 minutes) were combined for testing residual circumferential intima percentage and media thickness after EVA. RESULTS: Intact circumferential residual intima after the treatment was 21.3±4.9%, 18.2±7.4%, 15.7±2.4% and 8.9±2.0% using 0.5% (3 min), 0.5% (5 min), 1% (3 min) and 1% (5 min), respectively (R2=0.945; control sample: 97.6%). Media thickness after the treatment was 121.6±35.3 µm, 110.9±7.8 µm, 96.1±30.4 µm and 79.1±34.1 µm using 0.5% (3 min), 0.5% (5 min), 1% (3 min) and 1% (5 min), respectively (R2=0.990; control sample 125.7 µm). No significant modifications were detected analyzing the adventitia in all samples. CONCLUSIONS: EVA proved to be effective in venous wall destruction even with a very low SLAC and ctSA/VW (0.5% in 3 minutes), in quite large caliber veins. Direct comparisons with foam/liquid sclerotherapy should be done to confirm therapeutic effectiveness of these results, despite EVA has provided a maximized and controlled SA/VW contact time and ratio.
Subject(s)
Polidocanol , Sclerosing Solutions , Sclerotherapy , Tunica Intima , Tunica Media , Animals , Tunica Intima/pathology , Tunica Intima/surgery , Tunica Media/pathology , Sheep , Iliac Vein/surgery , Jugular Veins/surgery , Time Factors , Ablation Techniques , Models, Animal , Disease Models, AnimalABSTRACT
AIM: The authors set out to evaluate the correlations between three of the main morphological aortic parameters (elastic fibers - FE, collagen fibers - FCOL, and smooth muscle fibers - FM) and the cause of death. MATERIALS AND METHODS: Study groups included 25 cases died of a vascular disease (V_P), 37 cases died of a non-vascular disease (NV_P) and 28 cases died of a violent/suspect non-pathological cause of death (V_Dth), the latter group representing also the control group. Four aortic cross-sections (base, arch, thoracic, and abdominal regions) were collected during autopsy from the selected cases, fixed in 10% buffered formalin and first of all photographed together with a calibrating ruler. Then, they were embedded in paraffin, sectioned off at 4 µm and stained with Hematoxylin-Eosin (HE) and Orcein. The obtained histological slides were transformed into virtual slides. Fibrillary components amounts were using a custom-made software, developed in MATLAB (MathWorks, USA). Statistical tools used were Pearson's correlation test, t-test (two-sample assuming equal variances) and one-way analysis of variance (ANOVA) test. RESULTS AND DISCUSSIONS: The amounts of the three fibrillary components of the aortic tunica media had a synchronous variation in all aortic regions in each of the three groups, excepting FCOL in the group of patients died from vascular pathology, which presented only a trend of synchronous variation along the aorta. FE had their lowest values and FCOL had their highest values in patients died from vascular pathology. FCOL had always higher levels than FE in people died from any pathological condition, vascular or non-vascular. FM had always at least two times lower level than that of the other types of fibers, regardless of whether the person died due to a pathological condition or not. CONCLUSIONS: The different pathological conditions causing death are influencing the fibrillary composition of aortic tunica media. Further studies are required to reveal other changes in the morphology of aortic wall in particular and vascular wall in general that could be related with different pathological conditions affecting the entire organism.
Subject(s)
Aorta , Fludrocortisone , Humans , Cause of Death , Aorta/pathology , Tunica Media/pathology , Tunica Intima/pathologyABSTRACT
The most common inherited cause of vascular dementia and stroke, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), is caused by mutations in NOTCH3. Post-translationally altered NOTCH3 accumulates in the vascular media of CADASIL arteries in areas of the vessels that exhibit profound cellular degeneration. The identification of molecules that concentrate in the same location as pathological NOTCH3 may shed light on processes that drive cytopathology in CADASIL. We performed a two phase immunohistochemical screen of markers identified in the Human Protein Atlas to identify new proteins that accumulate in the vascular media in a pattern similar to pathological NOTCH3. In phase one, none of 16 smooth muscle cell (SMC) localized antigens exhibited NOTCH3-like patterns of expression; however, several exhibited disease-dependent patterns of expression, with antibodies directed against FAM124A, GZMM, MTFR1, and ST6GAL demonstrating higher expression in controls than CADASIL. In contrast, in phase two of the study that included 56 non-SMC markers, two proteins, CD63 and CTSH, localized to the same regions as pathological NOTCH3, which was verified by VesSeg, a customized algorithm that assigns relative location of antigens within the layers of the vessel. Proximity ligation assays support complex formation between NOTCH3 fragments and CD63 in degenerating CADASIL media. Interestingly, in normal mouse brain, the two novel CADASIL markers, CD63 and CTSH, are expressed in non-SMC vascular cells. The identification of new proteins that concentrate in CADASIL vascular media demonstrates the utility of querying publicly available protein databases in specific neurological diseases and uncovers unexpected, non-SMC origins of pathological antigens in small vessel disease.
Subject(s)
CADASIL , Dementia, Vascular , Mice , Animals , Humans , CADASIL/genetics , CADASIL/pathology , Receptors, Notch/genetics , Receptors, Notch/metabolism , Receptor, Notch3/genetics , Cerebral Infarction , Tunica Media/pathology , MutationABSTRACT
Mönckeberg medial calcinosis (MMC) is a potentially serious vasculopathy involving calcification of the arterial tunica media of the extremities, heart, and other viscera. There are a limited number of cases reported in the dental literature, usually associated with the facial artery. Although MMC is often discerned as an occult radiologic finding in middle-aged adults, its presence may serve as a harbinger for end-stage renal disease, diabetes, other pathologic processes, and possible regional hypoperfusion. The objective of this report is to feature an elderly patient with MMC of the facial and infraorbital arteries. In addition, a brief review of published cases of MMC and its differential diagnosis have been provided. It is recommended that affected patients be referred for a comprehensive medical assessment. Timely discovery of calcified arteries may improve patient outcomes.
Subject(s)
Calcinosis , Monckeberg Medial Calcific Sclerosis , Mouth, Edentulous , Middle Aged , Adult , Aged , Humans , Monckeberg Medial Calcific Sclerosis/pathology , Arteries/pathology , Tunica Media/pathology , Calcinosis/pathology , Face/pathologyABSTRACT
Over 200 million individuals worldwide are estimated to have peripheral artery disease (PAD). Although the term peripheral can refer to any outer branch of the vasculature, the focus of this review is on lower-extremity arteries. The initial sequelae of PAD often include movement-induced cramping pain in the hips and legs or loss of hair and thinning of the skin on the lower limbs. PAD progresses, sometimes rapidly, to cause nonhealing ulcers and critical limb ischemia which adversely affects mobility and muscle tone; acute limb ischemia is a medical emergency. PAD causes great pain and a high risk of amputation and ultimately puts patients at significant risk for major adverse cardiovascular events. The negative impact on patients' quality of life, as well as the medical costs incurred, are huge. Atherosclerotic plaques are one cause of PAD; however, emerging clinical data now shows that nonatherosclerotic medial arterial calcification (MAC) is an equal and distinct contributor. This ATVB In Focus article will present the recent clinical findings on the prevalence and impact of MAC in PAD, discuss the known pathways that contribute specifically to MAC in the lower extremity, and highlight gaps in knowledge and tools that limit our understanding of MAC pathogenesis.
Subject(s)
Peripheral Arterial Disease/etiology , Vascular Calcification/complications , Age Factors , Chronic Limb-Threatening Ischemia/etiology , Heart Disease Risk Factors , Humans , Lower Extremity/blood supply , Models, Cardiovascular , Peripheral Arterial Disease/pathology , Plaque, Atherosclerotic/complications , Quality of Life , Tunica Media/pathology , Vascular Calcification/genetics , Vascular Calcification/pathologyABSTRACT
Aortic aneurysms occur relatively frequently in the ascending thoracic aorta, but are rarely seen in patients with type 2 diabetes. Our aim was to evaluate inflammatory cell infiltration in the ascending aortic aneurysm wall in patients with diabetes without arterial hypertension (DM2 group, N=6) versus hypertensive non-diabetic patients (AH group, N=34). For histologic analysis, the sections were stained with hematoxylin-eosin and Movat pentachrome. The immunohistochemical staining was used to analyze the infiltration of pro-inflammatory (CD68) and anti-inflammatory macrophages (CD163), T helper (CD4) and T killer cells (CD8), and B (CD79a) and plasma cells (CD138) in all three layers of aneurysms of both groups. The statistical significance of the differences between groups was evaluated by ANOVA and the Welch test. In comparison to the AH group, the DM2 group developed less severe infiltration of pro-inflammatory macrophages (P=0.004) and B cells (P=0.025) in the tunica intima, and tunica media (P=0.049, P=0.007, respectively), and fewer plasma cells in the tunica media (P=0.024) and tunica adventitia (P=0.017). We found no significant differences in the number of T helper, T killer cells, and anti-inflammatory macrophages and in the amount of collagen and elastic fibers, ground substance, and smooth muscle cells in all three layers of the vessel wall. Except in tunica adventitia of DM2 group, there were more collagen fibers overall (P=0.025). Thus, we conclude that the histological structure of the aneurysm in diabetics without hypertension is almost the same as in hypertensive patients without diabetes. Diabetics had significantly less inflammatory infiltration in all three layers of the vessel wall, and more collagen fibers in tunica adventitia.
Subject(s)
Aortic Aneurysm , Diabetes Mellitus, Type 2 , Hypertension , Aortic Aneurysm/pathology , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/pathology , Humans , Hypertension/complications , Hypertension/pathology , Tunica Intima/pathology , Tunica Media/pathologyABSTRACT
Arterial media calcification (AMC) is predominantly regulated by vascular smooth muscle cells (VSMCs), which transdifferentiate into pro-calcifying cells. In contrast, there is little evidence for endothelial cells playing a role in the disease. The current study investigates cellular functioning and molecular pathways underlying AMC, respectively by, an ex vivo isometric organ bath set-up to explore the interaction between VSMCs and ECs and quantitative proteomics followed by functional pathway interpretation. AMC development, which was induced in mice by dietary warfarin administration, was proved by positive Von Kossa staining and a significantly increased calcium content in the aorta compared to that of control mice. The ex vivo organ bath set-up showed calcified aortic segments to be significantly more sensitive to phenylephrine induced contraction, compared to control segments. This, together with the fact that calcified segments as compared to control segments, showed a significantly smaller contraction in the absence of extracellular calcium, argues for a reduced basal NO production in the calcified segments. Moreover, proteomic data revealed a reduced eNOS activation to be part of the vascular calcification process. In summary, this study identifies a poor endothelial function, next to classic pro-calcifying stimuli, as a possible initiator of arterial calcification.
Subject(s)
Endothelial Cells/pathology , Tunica Media/drug effects , Vascular Calcification/chemically induced , Vascular Calcification/pathology , Warfarin/pharmacology , Animals , Aorta/drug effects , Aorta/metabolism , Calcification, Physiologic/drug effects , Calcium/metabolism , Cell Transdifferentiation/drug effects , Endothelial Cells/metabolism , Male , Mice , Mice, Inbred DBA , Muscle, Smooth, Vascular/drug effects , Muscle, Smooth, Vascular/metabolism , Muscle, Smooth, Vascular/pathology , Myocytes, Smooth Muscle/drug effects , Myocytes, Smooth Muscle/metabolism , Myocytes, Smooth Muscle/pathology , Osteogenesis/drug effects , Tunica Media/metabolism , Tunica Media/pathology , Vascular Calcification/metabolismABSTRACT
BACKGROUND: Arterial medial calcification (AMC) is associated with a high incidence of cardiovascular risk in patients with type 2 diabetes and chronic kidney disease. Here, we tested whether hydrogen sulfide (H2S) can prevent AMC in rats with diabetic nephropathy (DN). METHODS: DN was induced by a single injection of streptozotocin and high-fat diet (45% kcal as fat) containing 0.75% adenine in Sprague-Dawley rats for 8 weeks. RESULTS: Rats with DN displayed obvious calcification in aorta, and this was significantly alleviated by Sodium Hydrosulfide (NaHS, a H2S donor, 50 µmol/kg/day for 8 weeks) treatment through decreasing calcium and phosphorus content, ALP activity and calcium deposition in aorta. Interestingly, the main endogenous H2S generating enzyme activity and protein expression of cystathionine-γ-lyase (CSE) were largely reduced in the arterial wall of DN rats. Exogenous NaHS treatment restored CSE activity and its expression, inhibited aortic osteogenic transformation by upregulating phenotypic markers of smooth muscle cells SMα-actin and SM22α, and downregulating core binding factor α-1 (Cbfα-1, a key factor for bone formation), protein expressions in rats with DN when compared to the control group. NaHS administration also significantly reduced Stat3 activation, cathepsin S (CAS) activity and TGF-ß1 protein level, and improved aortic elastin expression. CONCLUSIONS: H2S may have a clinical significance for treating AMC in people with DN by reducing Stat3 activation, CAS activity, TGF-ß1 level and increasing local elastin level.
Subject(s)
Aorta/drug effects , Aortic Diseases/prevention & control , Diabetic Nephropathies/drug therapy , Hydrogen Sulfide/pharmacology , Tunica Media/drug effects , Vascular Calcification/prevention & control , Animals , Aorta/metabolism , Aorta/pathology , Aortic Diseases/etiology , Aortic Diseases/metabolism , Aortic Diseases/pathology , Cathepsins/metabolism , Diabetic Nephropathies/complications , Diabetic Nephropathies/metabolism , Disease Models, Animal , Elastin/metabolism , Male , Rats, Sprague-Dawley , STAT3 Transcription Factor/metabolism , Transforming Growth Factor beta1/metabolism , Tunica Media/metabolism , Tunica Media/pathology , Vascular Calcification/etiology , Vascular Calcification/metabolism , Vascular Calcification/pathologyABSTRACT
Endothelial-mesenchymal transition (EndMT) is a form of endothelial dysfunction wherein endothelial cells acquire a mesenchymal phenotype and lose endothelial functions, which contributes to the pathogenesis of intimal hyperplasia and atherosclerosis. The mitogen activated protein kinase 7 (MAPK7) inhibits EndMT and decreases the expression of the histone methyltransferase Enhancer-of-Zeste homologue 2 (EZH2), thereby maintaining endothelial quiescence. EZH2 is the catalytic subunit of the Polycomb Repressive Complex 2 that methylates lysine 27 on histone 3 (H3K27me3). It is elusive how the crosstalk between MAPK7 and EZH2 is regulated in the endothelium and if the balance between MAPK7 and EZH2 is disturbed in vascular disease. In human coronary artery disease, we assessed the expression levels of MAPK7 and EZH2 and found that with increasing intima/media thickness ratio, MAPK7 expression decreased, whereas EZH2 expression increased. In vitro, MAPK7 activation decreased EZH2 expression, whereas endothelial cells deficient of EZH2 had increased MAPK7 activity. MAPK7 activation results in increased expression of microRNA (miR)-101, a repressor of EZH2. This loss of EZH2 in turn results in the increased expression of the miR-200 family, culminating in decreased expression of the dual-specificity phosphatases 1 and 6 who may repress MAPK7 activity. Transfection of endothelial cells with miR-200 family members decreased the endothelial sensitivity to TGFß1-induced EndMT. In endothelial cells there is reciprocity between MAPK7 signaling and EZH2 expression and disturbances in this reciprocal signaling associate with the induction of EndMT and severity of human coronary artery disease.
Subject(s)
Cell Transdifferentiation/physiology , Coronary Artery Disease/pathology , Endothelium, Vascular/pathology , Enhancer of Zeste Homolog 2 Protein/physiology , Mesoderm/pathology , Mitogen-Activated Protein Kinase 7/physiology , Signal Transduction/physiology , Tunica Intima/pathology , 3' Untranslated Regions/genetics , Coronary Artery Disease/enzymology , Coronary Stenosis/enzymology , Coronary Stenosis/pathology , Dual Specificity Phosphatase 1/biosynthesis , Dual Specificity Phosphatase 1/genetics , Dual Specificity Phosphatase 6/biosynthesis , Dual Specificity Phosphatase 6/genetics , Endothelium, Vascular/enzymology , Enzyme Activation , Gene Expression Regulation , Genes, Reporter , Histone Code , Human Umbilical Vein Endothelial Cells , Humans , Hyperplasia , Mesoderm/enzymology , MicroRNAs/biosynthesis , MicroRNAs/genetics , Tunica Media/pathologyABSTRACT
Objective: Atheromatous fibrous caps are produced by smooth muscle cells (SMCs) that are recruited to the subendothelial space. We tested whether the recruitment mechanisms are the same as in embryonic artery development, which relies prominently on Notch signaling to form the subendothelial medial SMC layers. Approach and Results: Notch elements were expressed in regions of fibrous cap in human and mouse plaques. To assess the causal role of Notch signaling in cap formation, we studied atherosclerosis in mice where the Notch pathway was inactivated in SMCs by conditional knockout of the essential effector transcription factor RBPJ (recombination signal-binding protein for immunoglobulin kappa J region). The recruitment of cap SMCs was significantly reduced without major effects on plaque size. Lineage tracing revealed the accumulation of SMC-derived plaque cells in the cap region was unaltered but that Notch-defective cells failed to re-acquire the SMC phenotype in the cap. Conversely, to analyze whether the loss of Notch signaling is required for SMC-derived cells to accumulate in atherogenesis, we studied atherosclerosis in mice with constitutive activation of Notch signaling in SMCs achieved by conditional expression of the Notch intracellular domain. Forced Notch signaling inhibited the ability of medial SMCs to contribute to plaque cells, including both cap SMCs and osteochondrogenic cells, and significantly reduced atherosclerosis development. Conclusions: Sequential loss and gain of Notch signaling is needed to build the cap SMC population. The shared mechanisms with embryonic arterial media assembly suggest that the cap forms as a neo-media that restores the connection between endothelium and subendothelial SMCs, transiently disrupted in early atherogenesis.
Subject(s)
Atherosclerosis/metabolism , Muscle, Smooth, Vascular/metabolism , Myocytes, Smooth Muscle/metabolism , Plaque, Atherosclerotic , Receptors, Notch/metabolism , Tunica Media/metabolism , Actins/genetics , Actins/metabolism , Animals , Arteries/metabolism , Arteries/pathology , Atherosclerosis/genetics , Atherosclerosis/pathology , Cell Lineage , Cells, Cultured , Disease Progression , Fibrosis , Humans , Immunoglobulin J Recombination Signal Sequence-Binding Protein/genetics , Immunoglobulin J Recombination Signal Sequence-Binding Protein/metabolism , Jagged-1 Protein/genetics , Jagged-1 Protein/metabolism , Male , Mice, Inbred C57BL , Mice, Knockout , Muscle, Smooth, Vascular/pathology , Myocytes, Smooth Muscle/pathology , Phenotype , Rats , Receptors, Notch/genetics , Signal Transduction , Tunica Media/pathologyABSTRACT
AIM: The aim of this study was to detect macrovascular findings in systemic sclerosis (SSc) by means of color Doppler ultrasonography (CDUS) and to evaluate the relationship between the laboratory and clinical findings in the setting of the disease. METHODS: This was a cross-sectional study. Eighty-eight patients were included in the study. CDUS examinations of the bilateral carotid, vertebral, and peripheral arteries were performed. The presence of macrovascular involvement was investigated and recorded, and its relationships with the clinical, laboratory, and cardiovascular risk factors were evaluated. RESULTS: An atheromatous plaque was found in 67.7% of the 1936 arteries examined by CDUS. Of these 1936 arteries, 37.4% demonstrated a narrowing of the intraluminal diameter. On the other hand, the carotid intima-media thickness (CIMT) was found to have increased in 55.7% of the patients. This increase was found to be statistically correlated with disease duration, the modified Rodnan Skin Thickness Score, and the Medsger Disease Activity Score. But no relation existed with the disease subtype, age, or cardiovascular risk factors. Arterial occlusion was detected in 10 patients. An association was found between the CIMT values and arterial occlusion. CONCLUSIONS: In this study, we examined the arteries by means of CDUS, and we detected structural alterations in the peripheral and carotid arteries. We witnessed that these macrovascular changes had a close association with certain features of SSc. We think there is a need for broader prospective studies in order to evaluate the contribution of these factors to the macrovascular changes stated in the article.
Subject(s)
Carotid Arteries/diagnostic imaging , Microvessels/pathology , Tunica Intima/diagnostic imaging , Tunica Intima/pathology , Tunica Media/diagnostic imaging , Tunica Media/pathology , Ultrasonography, Doppler, Color/methods , Adult , Aged , Arteries/pathology , Carotid Intima-Media Thickness , Cross-Sectional Studies , Female , Humans , Male , Microvessels/diagnostic imaging , Middle Aged , Predictive Value of Tests , Risk Factors , Scleroderma, Systemic/complications , Scleroderma, Systemic/diagnostic imagingABSTRACT
Coronary ectasia is a rare vessel defect that represents a pathological and incidental finding in routine coronary angiography performed for other coronary syndromes. This defect exposes to the risk of intra-coronary thrombosis by blood stasis due to the turbulent blood flow in those dilated areas that can lead to sudden death. We report an autopsy case of a male subject suddenly deceased. A medico-legal autopsy concluded an ischemic heart failure due to a vascular thrombosis by a blood clot in a coronary ectasia. Our case report aimed to discuss the mechanisms of sudden death attributed to coronary artery ectasia.
Subject(s)
Coronary Vessels/pathology , Death, Sudden, Cardiac/etiology , Dilatation, Pathologic/pathology , Adult , Collagen/metabolism , Coronary Thrombosis/pathology , Humans , Male , Myocardium/pathology , Pulmonary Edema/pathology , Tunica Media/metabolism , Tunica Media/pathologyABSTRACT
Background The underlying pathophysiology of coronary artery spasm (CAS) remains unclear. We aim to determine whether coronary artery medial layer thickness is associated with CAS using optical coherence tomography. Methods and Results A total of 50 patients with previous myocardial infarction underwent optical coherence tomography of the left anterior descending artery: 20 with CAS and 30 without CAS. Intimal and medial layer areas were measured by planimetric analysis of optical coherence tomography images. The medial area/external elastic membrane (EEM) area was significantly greater in patients with than without CAS (0.13±0.01 versus 0.09±0.01, respectively, P<0.01), whereas the intimal area/EEM area was similar in the 2 groups. In patients without CAS, the relationship of intimal area/EEM area with medial area/EEM area and coronary diameter response to intracoronary injection of acetylcholine was characterized by an inverted U-shaped curve (y=-1.85x2+0.81x+0.01, R2=0.43, P<0.001) and a U-shaped curve (y=2993.2x2-1359.6x+117.1, R2=0.53, P<0.001), respectively. Thus, the medial layer became thin and the contractile response became weak in coronary arteries with greater intimal area in the non-CAS patients. In contrast, in patients with CAS, the intimal area/EEM area had no significant relationship with the medial area/EEM area in either linear correlation analysis or quadratic regression analysis. Thus, even when the intimal layer thickened, the medial layer did not thin in patients with CAS. Conclusions The structural thickness of the coronary medial layer was increased in patients with CAS, which may provide mechanistic insight into the pathogenesis of CAS. Registration URL: https://www.upload.umin.ac.jp; Unique identifier: UMIN000018432.
Subject(s)
Coronary Vasospasm , Coronary Vessels , Tunica Media , Aged , Coronary Vasospasm/etiology , Coronary Vasospasm/pathology , Coronary Vasospasm/physiopathology , Coronary Vessels/pathology , Coronary Vessels/physiopathology , Correlation of Data , Female , Humans , Male , Myocardial Contraction/physiology , Myocardial Infarction/complications , Myocardial Infarction/pathology , Organ Size , Tomography, Optical Coherence/methods , Tunica Media/diagnostic imaging , Tunica Media/pathologyABSTRACT
Cardiovascular disease (CVD) is a major cause of death in patients with chronic kidney disease (CKD). Both conditions are rising in incidence as well as prevalence, creating poor outcomes for patients and high healthcare costs. Recent data suggests CKD to be an independent risk factor for CVD. Accumulation of uremic toxins, chronic inflammation, and oxidative stress have been identified to act as CKD-specific alterations that increase cardiovascular risk. The association between CKD and cardiovascular mortality is markedly influenced through vascular alterations, in particular atherosclerosis and vascular calcification (VC). While numerous risk factors promote atherosclerosis by inducing endothelial dysfunction and its progress to vascular structural damage, CKD affects the medial layer of blood vessels primarily through VC. Ongoing research has identified VC to be a multifactorial, cell-mediated process in which numerous abnormalities like mineral dysregulation and especially hyperphosphatemia induce a phenotype switch of vascular smooth muscle cells to osteoblast-like cells. A combination of pro-calcifying stimuli and an impairment of inhibiting mechanisms like fetuin A and vitamin K-dependent proteins like matrix Gla protein and Gla-rich protein leads to mineralization of the extracellular matrix. In view of recent studies, intercellular communication pathways via extracellular vesicles and microRNAs represent key mechanisms in VC and thereby a promising field to a deeper understanding of the involved pathomechanisms. In this review, we provide an overview about pathophysiological mechanisms connecting CKD and CVD. Special emphasis is laid on vascular alterations and more recently discovered molecular pathways which present possible new therapeutic targets.
Subject(s)
Atherosclerosis/etiology , Cardio-Renal Syndrome/etiology , Renal Insufficiency, Chronic/physiopathology , Vascular Calcification/etiology , Animals , Cardio-Renal Syndrome/classification , Cardio-Renal Syndrome/epidemiology , Cardio-Renal Syndrome/physiopathology , Disease Models, Animal , Endothelium, Vascular/physiopathology , Extracellular Vesicles/physiology , Heart Disease Risk Factors , Humans , Incidence , Inflammation , Mice , MicroRNAs/genetics , MicroRNAs/therapeutic use , Myocytes, Smooth Muscle/pathology , Rats , Renal Insufficiency, Chronic/complications , Tunica Media/pathology , Vascular Calcification/drug therapy , Vascular Calcification/prevention & control , Vitamin K 1/therapeutic use , Vitamin K Deficiency/complications , Vitamin K Deficiency/drug therapyABSTRACT
OBJECTIVE: Aneurysmal subarachnoid hemorrhage remains a devastating event with poorly understood pathophysiology. Previous studies have suggested that aneurysm wall inflammation may play a part in the development and potential rupture of aneurysms. The rabbit elastase aneurysm model is a well-established model, which produces aneurysms closely mimicking human cerebral aneurysms in flow dynamics and histopathology. The primary aim of this study was to correlate inflammatory changes after aneurysm formation using sequential vessel wall imaging with histopathologic analysis. A secondary aim was to evaluate the potential effect of gender and anti-inflammatory treatment with aspirin on this inflammatory response. METHODS: Twenty-seven New Zealand rabbits underwent surgery to create an aneurysm using elastase infusion at the right common carotid artery origin. Vessel wall imaging and histopathologic analysis was obtained at different time points after aneurysm creation. The rabbits were also randomized by gender and to treatment groups with or without aspirin. RESULTS: Histopathologic analysis revealed 3 distinct phases after aneurysm formation. These phases were an initial inflammatory phase, followed by a regeneration phase, and finally a connective tissue deposition phase. Vessel wall imaging demonstrated 2 distinct imaging patterns. No appreciable differences were seen in histology or imaging when comparing gender or treatment with aspirin. CONCLUSIONS: Inflammatory changes induced by the rabbit elastase aneurysm model can be correlated with histopathologic findings and observed on noninvasive vessel wall imaging. This may provide a method to study the inflammatory pathway as it pertains to aneurysmal development and subsequent rupture.
Subject(s)
Carotid Artery Diseases/chemically induced , Disease Models, Animal , Intracranial Aneurysm/complications , Magnetic Resonance Angiography , Pancreatic Elastase/toxicity , Rabbits/physiology , Animals , Aspirin/therapeutic use , Carotid Artery Diseases/diagnostic imaging , Carotid Artery Diseases/pathology , Carotid Artery, Common/diagnostic imaging , Carotid Artery, Common/drug effects , Carotid Artery, Common/pathology , Carotid Artery, Common/physiology , Disease Progression , Elastic Tissue/ultrastructure , Female , Hyperplasia , Infusions, Intra-Arterial , Intracranial Aneurysm/chemically induced , Intracranial Aneurysm/diagnostic imaging , Intracranial Aneurysm/drug therapy , Male , Myocytes, Smooth Muscle/pathology , Necrosis , Pancreatic Elastase/administration & dosage , Rabbits/immunology , Regeneration , Sex Characteristics , Single-Blind Method , Tunica Intima/pathology , Tunica Media/pathology , Vasculitis/drug therapy , Vasculitis/etiology , Vasculitis/pathologyABSTRACT
BACKGROUND: Kawasaki disease (KD) is a systemic vasculitis syndrome that occurs most frequently in children. Most clinical and pathological studies have focused on its coronary artery lesions. To date, no detailed studies of the aorta have been conducted. We studied KD autopsy cases with the aims of clarifying the time-course of changes in aortic lesions, the differences in the inflammatory cells and degree of inflammation at various aortic sites, and the progression of the inflammation. MATERIALS AND METHODS: The study materials were aortic specimens taken from 37 KD autopsy cases (acute phase: 19; remote phase: 18). Twenty-seven of the cases also had coronary aneurysms. We chose 3 aortic sites, i.e., the thoracic aorta, aortic root and aortic bifurcation, and we histologically observed and compared those sites in regard to the changes with time, the kinds of infiltrating cells and the number of inflammatory cells. We also observed the relationship between the vasa vasorum and inflammatory cell localization in the tunica media, and examined the progression of inflammation in the tunica media. RESULTS: Destruction of the vascular architecture was not seen in any of the 37 cases, but inflammatory cell infiltration was observed in 90% of the acute-phase cases. The inflammatory cell infiltration involved the tunica intima and tunica adventitia of the aorta on the 6th disease-day, and all layers of the aorta on the 13th disease-day; the infiltration peaked on the 18th disease-day. The infiltration gradually disappeared thereafter, and no significant infiltration was seen in the remote phase. The infiltrating inflammatory cells consisted mainly of CD163-positive macrophages. Comparison of the 3 sites of the aorta showed that the inflammatory cell infiltration was more severe in the aortic root and aortic bifurcation than in the thoracic aorta. The progression of inflammation to the aortic tunica media from the adventitia showed 2 patterns: 1 in which macrophages were aggregated around the vasa vasorum; and a second in which there was no such aggregation around the vasa vasorum, but there was diffuse inflammatory cell infiltration of the tunica media. In addition to this, there were findings of direct infiltration of cells from the tunica intima into the tunica media. CONCLUSION: Inflammation in KD occurs in the aorta. The changes with time and the kinds of infiltrating cells were the same as reported to date for coronary arteries in KD. There were differences in the degree of inflammation among the 3 aortic sites. It can be thought that the inflammation from the adventitia to the media progresses via the vas vasorum, and also, there is a possibility of spreading directly. From the intima to the media, inflammation spreads directly. However, formation of aneurysms and destruction of the vascular architecture of the aorta were absent in this study, unlike in coronary arteries.
Subject(s)
Aorta, Thoracic/pathology , Aortitis/pathology , Mucocutaneous Lymph Node Syndrome/pathology , Adolescent , Adventitia/immunology , Adventitia/pathology , Antigens, CD/analysis , Antigens, Differentiation, Myelomonocytic/analysis , Aorta, Thoracic/immunology , Aortitis/immunology , Aortitis/mortality , Autopsy , Biomarkers/analysis , Case-Control Studies , Child , Child, Preschool , Disease Progression , Female , Humans , Infant , Macrophages/immunology , Macrophages/pathology , Male , Mucocutaneous Lymph Node Syndrome/immunology , Mucocutaneous Lymph Node Syndrome/mortality , Prognosis , Receptors, Cell Surface/analysis , Tunica Media/immunology , Tunica Media/pathology , Vasa Vasorum/immunology , Vasa Vasorum/pathologyABSTRACT
In 1987, Seymour Glagov observed that arteries went through a two-stage remodeling process as a result of plaque growth: first, a compensatory phase where the lumen area remains approximately constant and second, an encroachment phase where the lumen area decreases over time. In this paper, we investigate the effect of growth anisotropy on Glagov remodeling in five different cases: pure radial, pure circumferential, pure axial, isotropic and general anisotropic growth where the elements of the growth tensor are chosen to minimize the total energy. We suggest that the nature of anisotropy is inclined towards the growth direction that requires the least amount of energy. Our framework is the theory of morphoelasticity on an axisymmetric arterial domain. For each case, we explore their specific effect on the Glagov curves. For the latter two cases, we also provide the changes in collagen fiber orientation and length in the intima, media and adventitia. In addition, we compare the total energy produced by growth in radial, circumferential and axial direction and deduce that using a radially dominant anisotropic growth leads to lower strain energy than isotropic growth.
Subject(s)
Atherosclerosis/etiology , Models, Cardiovascular , Vascular Remodeling/physiology , Adventitia/physiology , Adventitia/physiopathology , Arteries/pathology , Arteries/physiopathology , Atherosclerosis/pathology , Atherosclerosis/physiopathology , Biomechanical Phenomena , Collagen/metabolism , Elasticity , Hemodynamics/physiology , Humans , Mathematical Concepts , Plaque, Atherosclerotic/etiology , Plaque, Atherosclerotic/pathology , Plaque, Atherosclerotic/physiopathology , Tunica Intima/pathology , Tunica Intima/physiopathology , Tunica Media/pathology , Tunica Media/physiopathologyABSTRACT
OBJECTIVES: Aging causes stiffness and decreased function of the renal artery (RA). Histological study with light microscopy can reveal microscopic structural remodeling but no functional changes. The present study aimed to clarify the association between structural and functional aging of the RA through the use of scanning acoustic microscopy. METHODS: Formalin-fixed, paraffin-embedded cross-sections of renal arteries from 64 autopsy cases were examined. Speed-of-sound (SOS) values of three layers, which correspond to the stiffness, were compared among different age groups. SOS of the tunica media was examined in terms of blood pressure (BP) and SOS of the ascending aorta. Vulnerability to proteases was assessed by SOS reduction after collagenase treatment. RESULTS: The tunica intima presented inward hypertrophy with luminal narrowing, and the tunica media showed outward hypertrophic remodeling with aging. SOS of the tunica media and internal and external elastic laminae showed a reverse correlation with age. SOS of the tunica media was negatively correlated with BP and strongly associated with that of the aorta. The tunica media of young RAs were more sensitive to collagenase compared with the old ones. CONCLUSIONS: Scanning acoustic microscopy is useful for observing the aging process of the RA. This technique simultaneously shows structural and mechanical information from each portion of the RA. In the process of aging, the RA loses contractile function and elasticity as a result of protease digestion. The tunica media and the internal and external elastic laminae exhibit reduced stiffness, but the tunica intima stiffens with atherosclerosis. As a consequence, the RA's outer shape changes from round to oval with inward and outward hypertrophy. This indicates that the inner resistant intima supports the mechanical weakness of the tunica media to compensate for an increase in BP with aging.