Aortic intimal resident macrophages are essential for maintenance of the non-thrombogenic intravascular state

Leukocytes and endothelial cells frequently cooperate to resolve inflammatory events. In most cases, these interactions are transient in nature and triggered by immunological insults. Here, we report that, in areas of disturbed blood flow, aortic endothelial cells permanently and intimately associate with a population of specialized macrophages. These macrophages are recruited at birth from the closing ductus arteriosus and share the luminal surface with the endothelium, becoming interwoven in the tunica intima. Anatomical changes that affect hemodynamics, such as in patent ductus arteriosus, alter macrophage seeding to coincide with regions of disturbed flow. Aortic resident macrophages expand in situ via direct cell renewal. Induced depletion of intimal macrophages leads to thrombin-mediated endothelial cell contraction, progressive fibrin accumulation and formation of microthrombi that, once dislodged, cause blockade of vessels in several organs. Together the findings reveal that intravascular resident macrophages are essential to regulate thrombin activity and clear fibrin deposits in regions of disturbed blood flow.

The Active Isoforms of MGP Are Expressed in Healthy and Varicose Veins without Calcification

Matrix Gla protein (MGP), a local inhibitor of tissue mineralization, is associated with vascular calcification. Depending on the carboxylation and phosphorylation status, MGP has active conformations, e.g., carboxylated MGP (cMGP) and phosphorylated MGP (pMGP), but also inactive conformations, e.g., uncarboxylated MGP (ucMGP) and dephosphorylated MGP (dpMGP). Our purpose was to assess the presence of all MGP conformations in healthy veins (HV) and varicose veins (VV), concurrently with the analysis of circulating total MGP (tMGP) before and after the surgical stripping of VV. We collected samples from the great saphenous vein, considered as control group, and tissue from VV, designated as VV group. Plasma levels of tMGP were significantly decreased after the surgical removal of the VV (before 59.5 ± 17.2 vs. after 38.1 ± 11.3, p < 0.001). By using immunohistochemistry staining, we identified local cMGP and pMGP in the control and VV groups, both without calcification, while ucMGP and dpMGP were absent. cMGP was observed in the nucleus and cytoplasm and pMGP in the nucleus of cells belonging to the tunica media, tunica intima and vasa vasorum. Therefore, the active conformations of MGP (cMGP and pMGP) are prevalent in HV and VV without calcification, affirming their anti-calcifying role in veins.

Bridging Coronary Physiology into Clinical Application of Acute Coronary Syndrome

Normal arteries have three layers of structure, tunica intima, tunica media, and tunica adventitia. Intima tunica is the deepest layer of coronary arteries in which there are antithrombotic molecules such as heparin sulfate, thrombomodulin, and plasminogen activator. In addition, tunica intima also contains substances that regulate the contraction of tunica smooth muscle cell media, called nitric oxide (vasodilators) and prostacyclin (vasoconstrictors). Tunica intima and tunica media seem to be directly related to the atherosclerosis process. Meanwhile, the role of tunika adventisia is unknown. The accumulation of atherosclerotic lesions and hemodynamic stress factors and the degradation of extracellular matrix will cause susceptibility of atherosclerotic plaque fibrous capsules to rupture and form thrombus. Thrombus that occurs in the coronary condition causes acute coronary syndrome, characterized by typical symptoms such as chest pain depending on the thrombus formed. In studying acute coronary syndromes, of course it cannot be separated from understanding the physiology of coronary arteries and the process of atherosclerosis. Therefore, this article aims to briefly explain coronary physiology.

Neointimal hyperplasia regression using combined paclitaxel- mediated confocal dual pulse shock wave sonoporation therapy and catheter- based 90Y- mediated brachytherapy

Background and aims Intimal hyperplasia refers to proliferation and migration of vascular smooth muscle cells primarily in the tunica intima, resulting in arterial wall thickening and decreased arterial lumen size. Neointimal hyperplasia is the major cause of restenosis after percutaneous carotid interventions such as stenting or angioplasty. The aim of this study was to investigate the effect of combined shock wave enhanced sonoporation therapy and catheter-based 90Y-mediated β-brachytherapy on neointimal hyperplasia regression in an animal model, wherein diagnostic B-mode ultrasound is combined with therapy system, with a goal of increased safety. Methods Endothelial balloon catheter denudation of the abdominal aorta of golden Syrian hamsters was performed. Histopathologic evaluation confirmed neointimal hyperplasia formation in all of the hamsters' arteries. The treatment group underwent intravenous lipid-based encapsulated paclitaxel nanoparticles (10mg/kg)-mediated extracorporeal confocal dual pulse low-level focused electrohydraulic shock wave (V=15 kV, F=2 Hz, Impulses = 50 and V=10 kV, F=0.2 Hz, Impulses = 150) enhanced sonoporation therapy accompanied by catheter-based 90Y-mediated β-brachytherapy (90Y, 15 Gy), guided by simultaneous B-mode ultrasound imaging. Results B-mode ultrasound guided combined shock wave enhanced sonoporation therapy and β-brachytherapy was feasible and appeared safe for the targeting of stenosis in the aorta artery. Furthermore, pathological results showed a significant reduction in the mean value for smooth muscle hyperplasia cells density, lumen wall thickness and percentage of luminal cross- sectional area of stenosis in the treatment group compared with the other groups (p&lt;0.05). Conclusions Enhanced toxicity effect of paclitaxel, induced by enhanced sonoporation effect of shock wave therapy, due to inertial cavitation effect of collapsed capsules and dual pulse system application accompanied by apoptotic effect of brachytherapy, can cause to neointimal hyperplasia regression. Combined shock wave enhanced sonoporation therapy and β-brachytherapy is significantly associated with reduced aorta artery stenosis in hamsters. The mechanism may relate to reduced smooth muscle hyperplasia cells and inflammation in the tunica intima. FUNDunding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Mehrad Research Lab

Impact of solitons on the progression of initial lesion in aortic dissection

Aortic dissection (AD) is the most common catastrophic disease reported at cardiovascular emergency in hospitals. Herein, a tear in the tunica intima results into separation of layers of aortic wall leading to rupture and torrential bleed. Hypoxia and oxidative stress are associated with AD. The release of hypoxia inducible factor (HIF)-1[Formula: see text] from the initial flap lesion in the tunica intima is the basis for aneurysmal prone factors. We framed a boundary value problem (BVP) to evaluate homeostatic saturation for oxygen dynamics using steady-state analysis. We prove uniqueness and existence of the solution of the BVP for gas exchange at capillary–tissue interface as a normal physiological function. Failure of homeostatic mechanism establishes hypoxia, a new quasi-steady-state in AD. We model permeation of two-layer fluid comprised of blood and HIF-1[Formula: see text] through tunica media as a generalized [Formula: see text]-dimensional nonlinear evolution equation and solve it using Lie group of transformations method. We note that the two-layer fluid permeates the tunica media as solitary wave including solitons such as bright soliton, dark soliton, peregrine soliton, topological soliton, kink soliton, breather soliton and multi-soliton complex. Also, we introduce the main result and discuss the implications of soliton solution, using graphic interpretation, to describe the early stage of progression of AD.

Implications of Endothelial Cell-Mediated Dysfunctions in Vasomotor Tone Regulation

Cardiovascular diseases (CVD) constitute the major cause of death worldwide and show a higher prevalence in the adult population. The human umbilical cord consistsof two arteries and one vein, both composed of three tunics. The tunica intima, lined with endothelial cells, regulates vascular tone through the production/release of vasoregulatory substances. These substances can be vasoactive factors released by endothelial cells (ECs) that cause vasodilation (NO, PGI2, EDHF, and Bradykinin) or vasoconstriction (ET1, TXA2, and Ang II) depending on the cell type (ECs or SMC) that reacts to the stimulus. Vascular studies using ECs are important for the analysis of cardiovascular diseases since endothelial dysfunction is an important CVD risk factor. In this paper, we will address the morphological characteristics of the human umbilical cord and its component vessels. the constitution of the vascular endothelium, and the evolution of human umbilical cord-derived endothelial cells when isolated. Moreover, the role played by the endothelium in the vasomotor tone regulation, and how it may be associated with the existence of CVD, were discussed.

Systemic mucoid degeneration of the arterial tunica intima in a young dog

A 27-mo-old, spayed female mixed-breed dog was presented with left forelimb pain, which progressed to full thickness necrosis of the soft tissues of multiple limbs. Clinical imaging and postmortem examination suggested multiple large arterial thromboemboli. Histologic examination of vascular lesions revealed markedly thickened tunica intima with polypoid intraluminal projections, which partially to entirely occluded the arterial lumen. The expanded tunica intima was comprised of intimal accumulation of Alcian blue–positive matrix with scattered spindle-to-satellite cells. These cells were positive for von Willebrand factor and vimentin but negative for α–smooth muscle actin, suggesting endothelial origin. Deposition of the intimal mucoid matrix was observed in the elastic and muscular arteries associated with regional ischemic changes. Mucoid emboli, likely from fragmentation of proliferative intimal tissue, were identified in smaller vessels supplied by affected arteries. Based on these findings, we diagnosed systemic mucoid degeneration of the arterial tunica intima. Such systemic arterial degeneration characterized by deposition of mucoid matrix in the tunica intima has not been reported previously in dogs, to our knowledge, and should be distinguished from thromboembolism and other degenerative vascular diseases.

Managing pregnancy-related stroke risk with known bilateral internal carotid artery webs

Carotid webs are intraluminal shelf-like projections caused by thickening of the arterial tunica intima. Due to their projections forming a nidus for thrombus formation and subsequent embolus, they are considered to be a rare cause of ischaemic strokes. We report a case of a woman with a background of recurrent ischaemic strokes due to bilateral carotid webs who presented with a twin pregnancy. We use this case to discuss how her pregnancy-related stroke risk was subsequently medically managed.

Histological Study of Age-Related Changes of Internal Thoracic Artery – A Cross-Sectional Study from Calicut, India

BACKGROUND Internal thoracic artery (ITA) is the ideal graft material for coronary artery bypass grafting (CABG). It’s structural characteristics and resistance to atherosclerotic changes make it ideal for this. It is in this scenario that we attempted to study the histological characteristics and age-related changes. METHODS This cross-sectional study was done on stained slides of segments of ITAs obtained from 100 fresh cadavers during autopsy. Age range was between 20 – 80 years. The segments were collected at various rib levels constituting proximal, middle and distal segments. The wall parameters were measured and recorded. The specimens were grouped according to age into six groups with intervals of 10 years and analysis of variance (ANOVA) test were conducted on the samples using Statistical Package for Social Science (SPSS) software. RESULTS The mean thickness of tunica intima in the proximal segment of 100 specimens was 26.792 µm, tunica media was 171.437µm and the thickness increased significantly with age with (F = 33.038, P = 0.00), (F = 87.910, P = 0.00) respectively. In one specimen, the intimal thickening increased to 96.325 µm. The mean thickness of tunica intima in the middle segment was 19.665 µm, tunica media was 172.302 µm and it increased significantly with age with (F = 71.885, P = 0.00), (F = 85.481, P = 0.00) respectively. The mean thickness of tunica intima in the distal segment was 18.157 µm, tunica media was 146.278 µm and it increased significantly with age (F = 58.847, P = 0.00), (F = 66.137, P = 0.00) respectively. The intima media ratio (IMR) increased significantly with age. The IMR of proximal segment of 2 % specimens were found to be greater than 0.25 indicating atherosclerosis. The vessel wall parameters decreased from proximal to distal segments. CONCLUSIONS The vessel wall thickness and IMR was found to increase with age. The incidence of atherosclerosis was 2 % and in old age. It is clear that the ITA is the ideal graft for CABG in younger individuals. An understanding of these attributes of ITA will be helpful to the cardiothoracic surgeons. Moreover, the results of this study throw light on the vessel wall changes in the population of present times. Further clinical study is needed to assess the effect of other risk factors. KEY WORDS Internal Thoracic Artery, Tunica Intima, Tunica Media, Intima Media Ratio, Atherosclerosis

Comparative Study of Coronary Artery Proximal to Myocardial Bridge Segment

Introduction: The muscular segments which overlie the epicardial arteries are termed as myocardial bridges and the artery which travels through them are termed as tunnel arteries. These tunnel arteries get compressed during the systolic compression of the heart, thus partially or completely blocking the blood supply to the corresponding areas. Aim & Objectives: To assess the impact of these myocardial bridges on the proximal segment of the myocardial arteries. Methodology: The present study was cadaveric-based cross-sectional study. A total of 22 hearts which showed the presence of myocardial bridges were collected from two sources namely: cadaver dissections, autopsy. The hearts were clean and numbered. This was followed by fixation, dehydration, clearing, embedding, block formation, section cutting and staining. Result: The present study showed that there is a significant thickening in the tunica intima of the proximal to bridge segment of the coronary artery. The present study also noted that there is a marked thinning of the tunica media of the same segment. Conclusion: The present study concludes that there is a marked hyperplasia in the proximal segment of the myocardial bridges under tunica intima.