New Insights into Cervicofacial Vascular Anomalies.

Congenital cervicofacial vascular anomalies are extremely rare and present many difficulties in diagnosis and treatment requiring a multidisciplinary approach. Firstly, there is little consensus on this subject among head and neck specialists. There are two main types of vascular anomalies: vascular tumors and vascular malformations. Vascular malformations are also divided into malformations with slow blood flow (veins, lymphatics, capillaries or combined) and malformations with a fast blood flow (arteriovenous malformations and fistula). Vascular tumors like hemangiomas are known for their spontaneous involution with aging, while vascular malformations grow in dimensions with age. It is very important to choose the correct differential diagnosis between cervicofacial hemangiomas and vascular malformations for proper therapy management. Anamnesis and clinical exams help in raising suspicions about the real nature of a cervico-vascular anomaly. Furthermore, imaging brings in-depth details of the anomaly, ranging from ultrasound and contrast CT to MRI scanning and minimally invasive angiography. Angiography with selective embolization is rarely a curative procedure for arteriovenous malformations, being more suitable as a preliminary step before attempted surgical removal. Surgery is clearly necessary when there are aesthetic and functional deficits. Slow-flow vascular malformations present a reduced morbidity, and in cases without involution, the surgical ablation is reserved for the cases with aesthetic dysfunctions or psychological trauma. Lymphatic malformations must undergo surgical ablation when they are associated with mass effects and compression of great vessels or aerial viscera. The prognosis after surgical removal is good, with a low rate of recurrence or morbidity. Fast-flow vascular malformations require a combined approach, with embolization and excision in the next 48 h for safety reasons. Removal may be followed by reconstructive surgery depending on the location and dimensions of the malformation, with a possible secondary recovery of the normal microscopic vessels. Some of the masses may hinder the normal airflow and swallowing. Pathology is the gold standard for confirming the clinical and imaging diagnosis.

Pharmacological Inhibition of Lysine-Specific Demethylase 1A Reduces Atherosclerotic Lesion Formation in Apolipoprotein E-Deficient Mice by a Mechanism Involving Decreased Oxidative Stress and Inflammation; Potential Implications in Human Atherosclerosis.

Dysregulated epigenetic mechanisms promote transcriptomic and phenotypic alterations in cardiovascular diseases. The role of histone methylation-related pathways in atherosclerosis is largely unknown. We hypothesize that lysine-specific demethylase 1A (LSD1/KDM1A) regulates key molecular effectors and pathways linked to atherosclerotic plaque formation. Human non-atherosclerotic and atherosclerotic tissue specimens, ApoE-/- mice, and in vitro polarized macrophages (Mac) were examined. Male ApoE-/- mice fed a normal/atherogenic diet were randomized to receive GSK2879552, a highly specific LSD1 inhibitor, or its vehicle, for 4 weeks. The mRNA and protein expression levels of LSD1/KDM1A were significantly elevated in atherosclerotic human carotid arteries, atherosclerotic aortas of ApoE-/- mice, and M1-Mac. Treatment of ApoE-/- mice with GSK2879552 significantly reduced the extent of atherosclerotic lesions and the aortic expression of NADPH oxidase subunits (Nox1/2/4, p22phox) and 4-hydroxynonenal-protein adducts. Concomitantly, the markers of immune cell infiltration and vascular inflammation were significantly decreased. LSD1 blockade down-regulated the expression of genes associated with Mac pro-inflammatory phenotype. Nox subunit transcript levels were significantly elevated in HEK293 reporter cells overexpressing LSD1. In experimental atherosclerosis, LSD1 mediates the up-regulation of molecular effectors connected to oxidative stress and inflammation. Together, these data indicate that LSD1-pharmacological interventions are novel targets for supportive therapeutic strategies in atherosclerosis.

Pharmacological inhibition of histone deacetylase reduces NADPH oxidase expression, oxidative stress and the progression of atherosclerotic lesions in hypercholesterolemic apolipoprotein E-deficient mice; potential implications for human atherosclerosis.

NADPH oxidase (Nox)-derived reactive oxygen species (ROS) are instrumental in all inflammatory phases of atherosclerosis. Dysregulated histone deacetylase (HDAC)-related epigenetic pathways have been mechanistically linked to alterations in gene expression in experimental models of cardiovascular disorders. Hitherto, the relation between HDAC and Nox in atherosclerosis is not known. We aimed at uncovering whether HDAC plays a role in mediating Nox up-regulation, oxidative stress, inflammation, and atherosclerotic lesion progression. Human non-atherosclerotic and atherosclerotic arterial samples, ApoE-/- mice, and in vitro polarized monocyte-derived M1/M2-macrophages (Mac) were examined. Male ApoE-/- mice, maintained on normal or high-fat, cholesterol-rich diet, were randomized to receive 10 mg/kg suberoylanilide hydroxamic acid (SAHA), a pan-HDAC inhibitor, or its vehicle, for 4 weeks. In the human/animal studies, real-time PCR, Western blot, lipid staining, lucigenin-enhanced chemiluminescence assay, and enzyme-linked immunosorbent assay were employed. The protein levels of class I, class IIa, class IIb, and class IV HDAC isoenzymes were significantly elevated both in human atherosclerotic tissue samples and in atherosclerotic aorta of ApoE-/- mice. Treatment of ApoE-/- mice with SAHA reduced significantly the extent of atherosclerotic lesions, and the aortic expression of Nox subtypes, NADPH-stimulated ROS production, oxidative stress and pro-inflammatory markers. Significantly up-regulated HDAC and Nox subtypes were detected in inflammatory M1-Mac. In these cells, SAHA reduced the Nox1/2/4 transcript levels. Collectively, HDAC inhibition reduced atherosclerotic lesion progression in ApoE-/- mice, possibly by intertwined mechanisms involving negative regulation of Nox expression and inflammation. The data propose that HDAC-oriented pharmacological interventions could represent an effective therapeutic strategy in atherosclerosis.

Histone Acetyltransferase-Dependent Pathways Mediate Upregulation of NADPH Oxidase 5 in Human Macrophages under Inflammatory Conditions: A Potential Mechanism of Reactive Oxygen Species Overproduction in Atherosclerosis.

Histone acetylation plays a major role in epigenetic regulation of gene expression. Monocyte-derived macrophages express functional NADPH oxidase 5 (Nox5) that contributes to oxidative stress in atherogenesis. The mechanisms of Nox5 regulation are not entirely elucidated. The aim of this study was to investigate the expression pattern of key histone acetyltransferase subtypes (p300, HAT1) in human atherosclerosis and to determine their role in mediating the upregulation of Nox5 in macrophages under inflammatory conditions. Human nonatherosclerotic and atherosclerotic tissue samples were collected in order to determine the expression of p300 and HAT1 isoforms, H3K27ac, and Nox5. In vitro determinations were done on human macrophages exposed to lipopolysaccharide in the absence or presence of histone acetyltransferase inhibitors. Western blot, immunohistochemistry, immunofluorescence, real-time PCR, transfection, and chromatin immunoprecipitation assay were employed. The protein levels of p300 and HAT1 isoforms, H3K27ac, and Nox5 were found significantly elevated in human atherosclerotic specimens. Immunohistochemistry/immunofluorescence staining revealed that p300, HAT1, H3K27ac, H3K9ac, and Nox5 proteins were colocalized in the area of CD45+/CD68+ immune cells and lipid-rich deposits within human atherosclerotic plaques. Lipopolysaccharide induced the levels of HAT1, H3K27ac, H3K9ac, and Nox5 and the recruitment of p300 and HAT1 at the sites of active transcription within Nox5 gene promoter in cultured human macrophages. Pharmacological inhibition of histone acetyltransferase significantly reduced the Nox5 gene and protein expression in lipopolysaccharide-challenged macrophages. The overexpression of p300 or HAT1 enhanced the Nox5 gene promoter activity. The histone acetyltransferase system is altered in human atherosclerosis. Under inflammatory conditions, HAT subtypes control Nox5 overexpression in cultured human macrophages. The data suggest the existence of a new epigenetic mechanism underlying oxidative stress in atherosclerosis.

Fibrous Skeleton of the Heart: Anatomic Overview and Evaluation of Pathologic Conditions with CT and MR Imaging.

The fibrous skeleton is concentrated at the base of the ventricular mass. It provides electrical insulation at the atrioventricular level and fibrous continuity for the leaflets of the mitral, aortic, and tricuspid valves. Its components include the fibrous trigones, the fibrous area of aortic-mitral continuity, the subvalvar collar of the mitral valve, the membranous septum, the interleaflet triangles, the tendon of Todaro, and likely the conus ligament. The majority of the mitral annulus is fibrous, but the only true fibrous part of the tricuspid annulus is where the valvar leaflets are attached to the central fibrous body. At the aortic annulus, the fibrous elements support only the noncoronary aortic sinus and parts of the right and left coronary sinuses. The ring-shaped annulus of the arterioventricular valves as localized with imaging techniques (imaging annulus) differs from the crown-shaped hemodynamic annulus of the arterial valves. The imaging annulus corresponds to the plane passing through the nadirs of the hinge-lines of the leaflets. The hinges of the pulmonary valve are not part of the fibrous skeleton. Computed tomography (CT) and magnetic resonance (MR) imaging are excellent modalities for evaluation of the anatomy, physiologic variations, and pathologic conditions of the fibrous skeleton. The submillimeter isotropic three-dimensional datasets obtained with CT and the high contrast resolution of MR imaging are the main advantages of these modalities in assessing anatomy. The function of the valves and associated annuli can best be studied with MR imaging. Pathologic conditions involving the area, including paravalvar leaks, abscesses, perforation, and pseudoaneurysms, usually occur as a complication of infective endocarditis or extensive calcifications after valvar surgery. MR imaging and CT can demonstrate these lesions equally well. CT is the preferred technique for showing the extent of calcifications in the fibrous skeleton. Large calcifications involving the central fibrous body can cause heart block by interfering with the normal function of the His bundle and its branches. ©RSNA, 2017.

The clinical anatomy of the right ventricle.

Because the systemic and pulmonary circulations are arranged in series, the right and left ventricles of the human heart have similar stroke volumes (with only minute beat-to-beat changes). Besides propelling the same volume of blood through the corresponding circulations, the two ventricles also share common structures such as the pericardium, the interventricular septum and the coronary arteries and veins-all of which complete the dynamic and integrated picture of the human heart. However, there are marked differences between the left and right ventricles as each is adapted to separate and dissimilar vascular beds, including particular reactivity to stress, hormones, and drugs. Of the two, the right ventricle (RV) has so far been either more difficult to approach from the diagnostic point of view or even overlooked, while the left ventricle (LV) has been considered the main pump, and diagnostic and therapeutic measures have been considered to apply equally to the LV and RV. This review article presents an update, portraying the RV from the clinical anatomical point of view, and endeavors to underscore the main particulars of the RV with clinical and surgical applications.

The clinical anatomy of high take-off coronary arteries.

A number of criteria are used in the literature to describe high take-off coronary arteries, which can in part, explain the divide in the literature on the pathological significance of this anomaly. This study presents the anatomical variations of high take-off coronary arteries to draw attention to the possible clinical implications they may cause during angiography and other surgical procedures. The English Literature was searched to review high take-off coronary arteries. A high take-off coronary artery arising at least 1 cm in adults or 20% the depth of the sinus in children above the sinutubular junction, is considered of greater clinical relevance and was included in our meta-analysis. High take-off coronaries by other criteria was also included as part of the comprehensive review. Exclusion criteria were reports made in case studies or case reviews. The prevalence of high take-off coronary arteries in our study was 26 of 12,899 (0.202%). High take-off coronary arteries were found to originate up to 5 cm above the sinutubular junction. Right coronary arteries made up 84.46% of high take-off coronary arteries reported in the literature. Three (0.023%) cases that originated more than one centimeter above the sinutubular junction was associated with sudden cardiac death. This is a higher reported association than in studies that used other criteria for classification. It is important for clinicians to recognize the importance of correctly diagnosing high take-off coronary arteries in patients with coexisting cardiac morbidities so that suitable management plans can be developed.

The clinical anatomy of the conal artery.

Coronary arteries have been extensively described and recognized by gross anatomic studies. However, in the clinical setting, the recognition of the conal artery is essential during coronary angiography, as well as certain congenital heart conditions such as tetralogy of Fallot. In order to provide a complete anatomic and physiologic correlation of the actual incidence and distribution of the conal artery we examined 300 formalin fixed hearts with gross dissections and 300 coronary angiograms. The conal artery was identified in all hearts examined and five main patterns were recognized. In Type A (193, 32.1%), the conal artery arose as a branch of the right coronary artery (RCA); in Type B (96, 16%), the conal artery arose from the common coronary ostium with the RCA; in Type C (242, 40.3%), the conal artery took origin from the right aortic sinus as an independent artery; in Type D (48, 8%), multiple conal arteries were present and arose from the RCA as separate branches (32, 66.6%), from a common ostium with the RCA (8, 16.6%) or from the aortic sinus (8, 16.6%); in Type E (22, 3.6%), the conal artery arose as a branch of the right ventricular branch (17, 2.8%) or acute marginal artery (5, 0.8%). The relative prevalence of the five patterns as well as the morphology and the topography of the conal artery varied significantly with the degree of coronary luminal stenosis (as observed during angiography) and also with the degree of hypertrophied ventricular wall (as observed during gross dissections).

Postpartum Aortic Bifurcation Thrombosis on the Background of Thrombophilic Disorder.

Two main causes of arterial thrombosis are known: fi rst - atherosclerosis, extensively studied, and the second - atrial fi brillation. The lack of any risk factors and the occurrence at young age of a thrombotic event requires us to investigate possible other conditions, including inherited thrombophilia that is represented by a series of genetic disorders that increase the risk of thromboembolic disease. The role of thrombophilia in the occurrence of arterial thrombosis is inconsequential; this disorder is characterized by the tendency of developing venous thrombosis. We present a rare case of a 29 year old woman that presents an arterial thrombotic event subsequent to the caesarean section. The patient had a positive familial history for thrombotic events and a cavernous sinus thrombosis in personal history. Prophylactic treatment with unfractionated heparin throughout pregnancy was applied. At 31 weeks gestation the patient underwent cesarean surgery for nonreassuring fetal status, 2 weeks fetal intrauterine growth restriction and absent diastolic fl ow of uterine arteries. Three days post operatory arterial thrombosis is suspected. The context that led to this suspicion was paresthesia, color modifi cation of the right leg and abolished popliteal pulse. Angiographic-CT confi rmed the presumptive diagnosis. A cardiovascular, conservatory treatment was successfully applied. Considering the particularities of the presented case we discuss the occurrence of arterial thrombosis postpartum in the context of confi rmed thrombophilia by reviewing the specialized literature.

Human monocytes and macrophages express NADPH oxidase 5; a potential source of reactive oxygen species in atherosclerosis.

Monocytes (Mon) and Mon-derived macrophages (Mac) orchestrate important oxidative and inflammatory reactions in atherosclerosis by secreting reactive oxygen species (ROS) due, in large part, to the upregulated NADPH oxidases (Nox). The Nox enzymes have been extensively investigated in human Mon and Mac. However, the expression and functional significance of the Nox5 subtypes is not known. We aimed at elucidating whether Nox5 is expressed in human Mon and Mac, and examine its potential role in atherosclerosis. Human monocytic THP-1 cell line and CD14(+) Mon were employed to search for Nox5 expression. RT-PCR, Western blot, lucigenin-enhanced chemiluminescence and dihydroethidium assays were utilized to examine Nox5 in these cells. We found that Nox5 transcription variants and proteins are constitutively expressed in THP-1 cells and primary CD14(+) Mon. Silencing of Nox5 protein expression by siRNA reduced the Ca(2+)-dependent Nox activity and the formation of ROS in Mac induced by A23187, a selective Ca(2+) ionophore. Exposure of Mac to increasing concentrations of IFNγ (5-100 ng/ml) or oxidized LDL (5-100 µg/ml) resulted in a dose-dependent increase in Nox5 protein expression and elevation in intracellular Ca(2+) concentration. Immunohistochemical staining revealed that Nox5 is present in CD68(+) Mac-rich area within human carotid artery atherosclerotic plaques. To the best of our knowledge, this is the first evidence that Nox5 is constitutively expressed in human Mon. Induction of Nox5 expression in IFNγ- and oxidized LDL-exposed Mac and the presence of Nox5 in Mac-rich atheroma are indicative of the implication of Nox5 in atherogenesis.

Coronary veins: comprehensive CT-anatomic classification and review of variants and clinical implications.

Recent developments in cardiac pacing and trans-coronary vein ablations have demonstrated the increasing value of imaging of the cardiac venous system (CVS), especially computed tomographic (CT) mapping of the coronary veins. In contrast to that for coronary arteries, the literature for coronary veins is scarce. Moreover, a complete, highly efficient, and clinically useful classification of the CVS is not as straightforward as for the coronary arteries. The CVS comprises polymorphous types of venous conduits with notable anatomic variations. Recent anatomic classification divides the cardiac veins into two main groups: tributaries of the greater CVS and tributaries of the lesser CVS, consisting of the thebesian vessels. The greater CVS is subdivided into two groups: coronary sinus and non-coronary sinus tributaries. Imaging information about the CVS in this review is useful for a better understanding of the spatial orientation of the CVS and furthers proper use of the correct nomenclature for this important system. The authors describe the clinical implications of the different imaging techniques for assessment of the coronary veins, where cardiac CT venous mapping has major advantages. The role of CT in anatomic classification, assessment of anatomic variants, and diagnosis of pathologic changes of the CVS is discussed. The authors also underscore the particular role of CT venous mapping for cardiac interventions, especially for left ventricular pacing in cardiac resynchronization therapy and in percutaneous mitral annuloplasty.

The clinical anatomy of the mitral valve.

As a result of the numerous clinical and surgical data accumulated so far, the classical image of the mitral valve-a bicuspid valve, with two leaflets and two papillary muscles-undergoes significant modifications. The valve, included into the larger concept of the mitral valvular complex unveils numerous important valences and characteristics, among which, some represent newer concepts, of clinical and surgical significance: the valvular complex is a subtle and finely-tuned system of elements acting in a coordinated manner; the mitral valve is an active valve and not a mere passive flap bordering the atrioventricular junction. Not least, the mitral valve contributes to the make up and function of the left ventricular outflow tract. The anatomical and functional interdependence between the mitral valve and the left ventricular myocardium is evident not only following their particularities of vascularization but also it is reflected in morbid states such as ischemic cardiac disease and dilated cardiomyopathy. All the new concepts and ideas, ask for a more profound study of the clinical anatomy of the mitral valve, underscoring the importance of a pertinent dialogue between specialists and by using a more appropriate and unitary terminology.

The Ross procedure: new insights into the surgical anatomy.

BACKGROUND: The precise knowledge of regional anatomical details is of utmost importance specially in complex procedures such as the Ross operation. This anatomical study offers a critical approach regarding the advantages, limits, and precautions for this procedure. METHODS: Using dissection techniques, magnifications up to x6 and nontraditional approaches, 68 fixed normal heart specimens were studied over a 2-year period. The details of surgical relevance such as the boundaries and relations of the pulmonary and aortic roots, their vascularization, and the number and distribution of the septal arteries are described. RESULTS: The aortic and pulmonary roots include interdependent elements functioning in a coordinated manner and establishing important relations with adjacent structures. Both coronary arteries vascularize the arterial roots. The infundibular branches from the right coronary artery are larger and more constant. The septal arteries establish important relations with the pulmonary infundibulum but their contribution to its vascularization is negligible. In this series, the main septal artery was the second, showing the longest retroinfundibular course. However, no constant relation was found between this vessel and the intraventricular landmarks. CONCLUSIONS: A novel approach was used by performing nontraditional dissections of the arterial roots and by studying their vascularization The depicted details are useful to the surgeon specializing in the Ross procedure and represent the basis for further research.

Chiari anomalies in the human right atrium.

Chiari anomalies in the human right atrium ostensibly are encountered rarely. There is only sporadic mention in the literature of these fenestrated, net-like valves of the inferior vena cava, coronary sinus, or various strands connecting these with other right atrial structures. The effects of such structural anomalies on heart function are unknown. We report here gross observations of the right atrial net from among 213 cadavers, 38 autopsied, and 11 fetal hearts. Histological and ultrastructural examination of inferior vena cava and coronary sinus valves demonstrated that only the anomalous coronary sinus valves contained cardiac muscle. Chiari anomalies typically have referred to perforations or tissue strands related to the inferior vena cava valve and possibly the coronary sinus valve. The anomaly commonly is cited as occurring in 2% of individuals, although there has been no study to support this. We observed Chiari malformations in 13.6% of the 213 cadaver hearts, and 10.5% of the autopsied hearts examined. Of these malformations, the coronary sinus valve was fenestrated most frequently. We propose the term "right atrial net" for "Chiari net," for anomalies involving valves of the inferior vena cava and coronary sinus, and strands within the right atrium connecting these valves with the crista terminalis, right atrial wall, or interatrial septum.