Muscular Arteries Research Articles

Abstract 4138674: Long-acting CRF2 receptor agonist, COR-1389, improves cardiopulmonary function in the rat model of Sugen plus hypoxia-induced pulmonary hypertension and right heart failure

Introduction: Urocortin-2 (UCN-2), a peptide which is part of the corticotropin-releasing factor (CRF) family, functions as an autocrine and paracrine factor, exerting its effects on cardiac and pulmonary function through agonism of CRF2 receptors. Although acute administration of UCN-2 has shown promise by improving heart and lung function in conditions like heart failure (HF) and pulmonary hypertension (PH), its limited stability impedes its chronic therapeutic use. Hypothesis: In this study, we explored the efficacy of COR-1389, a potent, selective and long-acting CRF2 agonist peptide, in the Sugen 5416 (VEGFR2 inhibitor, Su) combined with hypoxia (Hx) rat model of PH and right heart failure (RHF). Methods: To this aim, male adult Sprague Dawley rats were divided into three groups: Control rats (normoxia) were compared with rats injected subcutaneously with 20 mg/kg Sugen 5416 and exposed to chronic hypoxia for 3 weeks, followed by 2 weeks of normoxia. At 5 weeks, control rats and one SuHx group received subcutaneously vehicle (control and SuHx), while the third group received COR-1389 at a dose of 100 μg/kg every 4 days subcutaneously for 3 weeks (SuHx + COR-1389). At 8 weeks, cardiac and pulmonary hemodynamic functions of the three groups were evaluated using echocardiography and right heart catheterization, and heart and lung tissue were evaluated by histology and immunohistochemistry. Results: Compared to controls (n=10), SuHx exhibited increased mean pulmonary arterial pressure (mPAP), right ventricle (RV) hypertrophy (Fulton Index/body weight), muscularization of distal pulmonary arteries, RV fibrosis and cardiomyocyte hypertrophy, alongside reduced RV systolic function (Tricuspid Annular Plane Systolic Excursion, TAPSE) and cardiac output (CO). Conversely, compared to the SuHx + vehicle group (n=11), curative treatment with COR-1389 for 3 weeks in SuHx rats (n=13) led to enhanced RV systolic function (TAPSE) and CO, together with reductions in mPAP, RV hypertrophy, muscularization of pulmonary arteries, RV fibrosis and cardiomyocyte hypertrophy. Systolic blood pressure remained unchanged across all groups. Conclusion: These findings indicate that COR-1389 ameliorates the deteriorating cardiopulmonary parameters observed in the SuHx model and represents a promising approach for the treatment of PH and RHF.

Recruitment of CCR5-positive T cells in pulmonary vascular lesions in idiopathic- and connective tissue disease associated- pulmonary arterial hypertension

Abstract Background C-C chemokine receptor type 5 (CCR5) is a chemokine receptor predominantly expressed on leukocytes including T cells, macrophages, and dendritic cells, and is involved in the process by which T cells are attracted to specific tissues and organs. Although CCR5 has been shown to be expressed on macrophages and pulmonary artery smooth muscle cells in lung samples from human idiopathic pulmonary arterial hypertension (PAH) and some animal models, its expression on T cells in human PAH lungs has not been investigated. Purpose To investigate the immunohistochemical expression of CCR5 on T cells infiltrating in pulmonary vascular lesions of human PAH tissues, particularly from patients with idiopathic PAH and PAH associated with connective tissue disease (CTD-PAH), where inflammation has been implicated in the pathogenesis. Methods Subjects included 25 postmortem cases of idiopathic PAH (14 cases, a mean age of 34 ± 10 years, 8 female cases) and CTD-PAH (11 cases, 48 ± 13 years, all female). We performed immunohistochemistry using antibodies against CCR5 and CD3 (for T cells) on formalin-fixed paraffin-embedded sections. To semi-quantify, we selected the three small muscular pulmonary arteries (80-150 µm in external diameter) with the strongest CCR5-positive cell infiltration in each case, counted the number of positive cells, and the average were shown as the number of cells per vessel. Results In all cases, regardless of whether IPAH or CTD-PAH, a subset of infiltrating inflammatory cells into or accumulating around vessels was CCR5-positive. Specifically, CCR5-positive inflammatory cells were found in remodelled pulmonary arteries, such as plexiform lesions and constrictive lesions with intimal thickening and/or medial hypertrophy, as well as perivascular space. The average number of CCR5-positive cells per small muscular pulmonary artery was 8.1/vessel. Where pulmonary venous occlusive lesions were seen, CCR5-positive cells were also present in and around them. The majority of CCR5-positive inflammatory cells appeared to be T cells, based on morphology and CD3 immunopositivity in the serial sections. Conclusion(s) Activated T cells showing CCR5 immunopositivity were recruited to remodelled pulmonary vascular lesions in both idiopathic PAH and CTD-PAH. This implicates CCR5-positive T cells as a common key player and that CCR5 signalling is involved in the pathogenesis of PAH in concert with other inflammatory cells, vascular endothelial cells, and pulmonary artery smooth muscle cells.

Successful Pedal Bypass in a Patient With Pseudoxanthoma Elasticum.

Pseudoxanthoma elasticum (PXE) is a rare metabolic disease, causing calcification in the arterial media layer and further peripheral artery disease (PAD). A high rate of failure has been reported after endovascular and open surgical management of PAD among patients with PXE. Critical limb ischemia (CLI) rarely develops in PXE, and there are only few reports of its treatment. We present a case report of a 57year-old female diagnosed with pseudoxanthoma elasticum (PXE). She presented with critical limb ischemia (CLI) and was successfully treated with pedal bypass using the great saphenous vein. Despite obtaining suboptimal outcomes through the initial approach of percutaneous transluminal angioplasty to treat critical limb ischemia, the subsequent bypass operation proved to be a success. At the first follow-up appointment at 1month, the patient was asymptomatic and the ulceration had almost healed. The patient underwent an ultrasound examination at 3, 6, 12, and 24months after discharge, and the surveillance was uncomplicated. With a clear indication for surgery, limb-threatening ischemia can be successfully treated with distal bypass, if necessary, in patients with PXE similarly to atherosclerotic PADs. Appropriate diagnostic and surveillance imaging and the utilization of a multidisciplinary team are key components for effective management of PAD in patients with PXE.

Spontaneous Parasitic Pedunculated Myoma Presenting the Absence of Uterine Smooth Muscle Cells in the Stalk — A Case Report

A few cases of spontaneous parasitic myoma have been reported. However, its cause remains unidentified. We report a case of spontaneous parasitic pedunculated subserosal myoma with pathological findings presenting with the absence of uterine smooth muscle cells in the stalk observed during robotic-assisted laparoscopic hysterectomy. A 51-year-old patient (G1P0) with no prior surgical history underwent a robotic-assisted laparoscopic hysterectomy. An approximately 3 cm-pedunculated subserosal myoma was found attached to the retroperitoneum. The stalk was sealed and separated and the myoma with retroperitoneal adipose tissue was resected. The stalk was pathologically identified to lack uterine smooth muscle cells and contain only muscular arteries and fibrous connective tissues. Thus, it might be hypothesized that after the myoma received collateral parasitic blood flow from the attached retroperitoneum, the stalk degenerated, and uterine smooth muscle cells were lost through an unknown mechanism, possibly underlying the development of spontaneous parasitic myomas.

An inducible model for medial calcification based on matrix Gla protein deficiency

Calcific deposits in the arterial media have been associated with a number of metabolic and genetic disorders including diabetes, chronic kidney disease and generalized arterial calcification of infancy. The loss of Matrix Gla protein (MGP) leads to medial elastic lamina calcification (elastocalcinosis) in both humans and animal models. While MGP-deficient (Mgp-/-) mice have been used as a reliable model to study medial elastocalcinosis, these mice are difficult to maintain because of their fragility. Also, these mice are unsuitable for long-term calcification studies in relation to age and sex as most often they die prematurely. In order to circumvent these problems we generated Mgp-/-;ApoE-FGF23 mice, which in addition to the ablation of Mgp alleles, carries a transgene expressing the phosphaturic hormone FGF23. Increased FGF23 levels in the circulation and ensuing hypophosphatemia in these mice lead to a complete prevention of medial calcification until late adulthood. Interestingly, upon feeding a high phosphorus diet for 10 days, we were able to induce medial calcification in 3-week-old Mgp-/-;ApoE-FGF23 mice. Our mineral analyses showed that the calcific deposits in these mice were Our mineral analyses showed that the Ca/P % in the calcific deposits in these mice were comparable to that of 5-week-old Mgp-/- mice although the level of crystallinity differed. The aorta explants from Mgp-/-;ApoE-FGF23 mice resulted in elastocalcinosis in the presence of 2mM phosphate in the culture medium which was completely prevented by pyrophosphate analogue alendronate. Mgp-/-;ApoE-FGF23 mice will be suitable for future in vivo or ex vivo studies examining the effects of age, sex and mineralization inhibitors on medial elastocalcinosis.

Diabetes-Related Changes in Carotid Wall Properties: Role of Triglycerides.

Background/Objectives: This study compares the power of the radiofrequency (RF) signal reflected from the media layer (media power) of the common carotid artery (CCA) and the CCA stiffness between individuals with and without type 2 diabetes mellitus (T2DM). It also evaluates the associations of CCA media power with plasma glucose and lipid levels, as well as carotid stiffness. Methods: A total of 540 individuals, 115 with and 425 without T2DM (273 males, mean age = 64 ± 8 years) were studied using RF-based tracking of the right CCA. The following parameters were measured: CCA media thickness, luminal diameter, wall tensile stress (WTS), local pulse wave velocity (PWV), and media power. Results: Compared to the non-diabetic individuals, the T2DM patients had significantly higher CCA media thickness (652 ± 122 vs. 721 ± 138 microns, p < 0.005), luminal diameter (6.12 ± 0.78 vs. 6.86 ± 0.96 mm, p < 0.0005), media power (36.1 ± 4.8 vs. 39.3 ± 4.6, p < 0.0001), and PWV (7.65 ± 1.32 vs. 8.40 ± 1.89 m/s; p < 0.01), but comparable WTS (32.7 ± 10.4 vs. 33.1 ± 10.7 kPa; p = 0.25). In the entire population, CCA media power was independently associated with male sex, pulse pressure, current smoking, and T2DM; when T2DM was not included in the model, triglycerides emerged as an independent determinant of media power. The CCA PWV was independently associated with age, pulse pressure, media power, and T2DM. Conclusions: Our findings suggest the presence of structural changes in the arterial media of T2DM patients, leading to carotid stiffening and remodeling, aiming to preserve WTS. T2DM-related changes in arterial wall composition may be driven by high plasma triglyceride levels, which have previously been associated with both arterial stiffening and the incidence of CV events.

A viscoelastic constitutive framework for aging muscular and elastic arteries

The evolution of arterial biomechanics and microstructure with age and disease plays a critical role in understanding the health and function of the cardiovascular system. Accurately capturing these adaptative processes and their effects on the mechanical environment is critical for predicting arterial responses. This challenge is exacerbated by the significant differences between elastic and muscular arteries, which have different structural organizations and functional demands. In this study, we aim to shed light to these adaptive processes by comparing the viscoelastic mechanics of autologous thoracic aortas (TA) and femoropopliteal arteries (FPA) in different age groups. We have extended our fractional viscoelastic framework, originally developed for FPA, to both types of arteries. To evaluate this framework, we analyzed experimental mechanical data from TA and FPA specimens from 21 individuals aged 13 to 73 years. Each specimen was subjected to a multi-ratio biaxial mechanical extension and relaxation test complemented by bidirectional histology to quantify the structural density and microstructural orientations. Our new constitutive model accurately captured the mechanical responses and microstructural differences of the tissues and closely matched the experimentally measured densities. It was found that the viscoelastic properties of collagen and smooth muscle cells (SMCs) in both the FPA and TA remained consistent with age, but the viscoelasticity of the SMCs in the FPA was twice that of the TA. Additionally, changes in collagen nonlinearity with age were similar in both TA and FPA. This model provides valuable insights into arterial mechanophysiology and the effects of pathological conditions on vascular biomechanics. Statement of significanceDeveloping durable treatments for arterial diseases necessitates a deeper understanding of how mechanical properties evolve with age in response to mechanical environments. In this work, we developed a generalized viscoelastic constitutive model for both elastic and muscular arteries and analyzed both the thoracic aorta (TA) and the femoropopliteal artery (FPA) from 21 donors aged 13 to 73. The derived parameters correlate well with histology, allowing further examination of how viscoelasticity evolves with age. Correlation between the TA and FPA of the same donors suggest that the viscoelasticity of the FPA may be influenced by the TA, necessitating more detailed analysis. In summary, our new model proves to be a valuable tool for studying arterial mechanophysiology and exploring pathological impacts.

Effects of acupuncture on endothelial active factors and related autonomic neurotransmitters in spontaneous hypertension rats

To observe the effects of acupuncture at "antihypertensive acupoint prescription" on endothelial active factors and related autonomic neurotransmitters in spontaneous hypertension rats, and explore the vascular regulation and central regulation mechanisms of acupuncture for anti-hypertension. Thirty SPF grade male spontaneous hypertension rats were randomly divided into a model group (15 rats) and an acupuncture group (15 rats). Besides, 15 Wistar Kyoto rats were collected as a blank control group (normal group). In the acupuncture group, acupuncture was delivered at the "antihypertensive acupoint prescription" (bilateral "Renying" [ST 9], "Quchi" [LI 11], "Zusanli" [ST 36], "Taichong" [LR 3] and "Neiguan" [PC 6]), with needles retained for 30 min, once daily. The duration of intervention was 28 days. Every week, using the the irritation scale, the sign of sympathetic irritation was evaluated dynamically. The arterial blood pressure of the rats tail was determined, using non-invasive blood pressure measurement system. ELISA was adopted to detect the levels of calcitonin gene-related peptide (CGRP), nitric oxide (NO), endothelin-1 (ET-1), neuropeptide Y (NPY) in the serum. DAB chromogenic in situ hybridization (CISH) was provided to detect the mRNA expression of endothelial nitric oxide synthase (eNOS) in the internal carotid artery and the arcuate nucleus (ARC), and that of CGRP in the paraventricular nucleus posterior (PVP) and the ventrolateral medulla (VLM). Liquid chromatography-mass spectrometry (LC-MS) was used to detect the levels of epinephrine (E) and norepinephrine (NE) in the paraventricular nucleus anterior (PVA). Compared with the normal group, the irritation scores, systolic blood pressure and diastolic blood pressure were increased at each time point in the model group (P<0.05). When compared with the model group, the irritation scores after the intervention for 3 and 4 weeks, and systolic and diastolic blood pressure after intervention for 2, 3 and 4 weeks were reduced in the acupuncture group (P<0.05). In comparison with the normal group, the serum CGRP and NO levels of the rats were decreased (P<0.05), and the serum ET-1 and NPY levels, as well as E and EN levels in PVA were increased (P<0.05) in the model group. The levels of serum CGRP and NO were elevated (P<0.05), and the serum ET-1 and NPY levels, as well as E and EN levels of PVA were reduced (P<0.05) in the acupuncture group when compared with those of the model group. In the model group, the media of internal carotid artery exhibited thickening and remodeling, while the neuron volume in ARC was small. In the acupuncture group, every layer of internal carotid artery was acceptably arranged, and the parvicellular neuron of ARC was moderate in volume. For the in situ hybridization of eNOS mRNA for the rats of each group, the smooth muscle cells were predominantly expressed in each layer of the internal carotid artery, whereas the expression of parvicellular neurons was dominated in ARC. In the model group, the large and small neurosecretory cells were distributed sparsely in the nerves of PVP; in the acupuncture group, the cells of these two species were distributed regularly; and there were few species of glial cell in the VLM of either the model group or the acupuncture group. In each group, for the in situ hybridization of CGRP mRNA, the small neurosecretory cells were expressed predominately in the PVP, while, the expression of glial cell nuclei and the cell cytoplasm was dominated in the VLM. Compared with the normal group, the mRNA expression of eNOS in the internal carotid artery and ARC and that of CGRP mRNA in the PVP and VLM was decreased in the model group (P<0.05). In the acupuncture group, when compared with the model group, the mRNA expression of eNOS in the internal carotid artery and ARC and that of CGRP in the PVP and VLM was increased in the acupuncture group (P<0.05). Acupuncture at "antihypertensive acupoint prescription" can upregulate the level of vascular relaxing factors, downregulate the level of contracting factors, enhance the response of relaxing factors in targeting blood vessels and regulating the center. The mechanism may be related to the modulation of the sympathetic-adrenergic autonomic neurotransmitters in the paraventricular nucleus in spontaneous hypertension rats.

Urinary N-acetyl-D-glucosaminidase can predict bleeding after a percutaneous kidney biopsy

BackgroundA percutaneous kidney biopsy (PKB) allows nephrologists to make informed decisions for treating various kidney diseases; however, the risk of bleeding complications should be considered, given the vascularity of the kidney. Many studies have reported risk factors for bleeding events after a PKB. However, while urinary N-acetyl-β-D-glucosaminidase (NAG) is a useful biomarker of kidney disease severity, little is known about whether or not urinary NAG is related to the bleeding risk.MethodsMedical records of patients who underwent a PKB at the National Defense Medical College Hospital between October 2018 and October 2023 were retrospectively studied. Hemoglobin (Hb) loss ≥ 1 g/dL was defined as a bleeding event.ResultsOf the 213 patients, 110 (51.6%) were men, and the median age was 56 years old (interquartile range 40–71). The most frequent diagnosis on a PKB was IgA nephropathy (N = 72; 34.0%). Fifty-four patients (25.3%) experienced Hb loss ≥ 1 g/dL after a PKB, and urinary NAG/Cr levels before the biopsy were able to predict a bleeding event, with an area under the receiver operating characteristic curve of 0.65 (p = 0.005). Using the optimal cutoff value of 35 U/gCr, urinary NAG/Cr was found to be an independent risk factor by multiple logistic regression analysis (odds ratio 3.21, 95% confidence interval 1.42–7.27, p = 0.005). Even after adjusting for previously-reported risk factors, the elevated urinary NAG/Cr ratio remained a statistically significant variable. Compared with the pathological findings, only the severity of multilayered elastic laminae of the small muscular artery was associated with both urinary NAG/Cr levels (p = 0.008) and bleeding events (p = 0.03).ConclusionUrinary NAG successfully predicted not only the severity of kidney disorders but also bleeding events after a PKB. Arteriosclerosis in the kidneys may be the mechanism underlying these increased bleeding events.

Effect of caspase inhibitors on hemodynamics and inflammatory factors in ARDS model rats

To study the effects of caspase inhibitors on hemodynamics and inflammatory factors in acute respiratory distress syndrome (ARDS) model rats. Sixty healthy male Wistar rats were randomly divided into three groups, namely, the control group, ARDS group and ARDS + Caspase inhibitor group, with 20 rats in each group. The control group was intraperitoneally injected with 2 mL/kg saline, and the ARDS model group was established by intraperitoneally injecting 4 mg/kg Lipopolysaccharide (LPS), ARDS + Caspase inhibitor group was adminstered 20 mg/kg caspase inhibitor after intraperitoneal LPS injection. Changes in pulmonary arterial pressure (PAP) and mean arterial pressure (MAP) at 6 and 12 h before and after administration were recorded. Moreover, arterial blood gas was evaluated with a blood gas analyzer and changes in the partial pressure of O2 (PaO2), partial pressure of CO2 (PaCO2), partial pressure of O2/fraction of inspired O2 (PaO2/FiO2) were evaluated. In addition, the lung wet/dry weight (W/D) ratio and inflammatory factor levels in lung tissue were determined. Finally, pathological sections were used to determine the pulmonary artery media thickness (MT), MT percentage (MT%), and the degree of muscle vascularization. The pulmonary arterial pressure of rats was determined at several time points. Compared with the control group, the model group had a significantly increased pulmonary arterial pressure at each time point (P < 0.01), and the mean arterial pressure significantly increased at 6 h (P < 0.05). Compared with that of rats in the model group, the pulmonary arterial pressure of rats in drug administration group was significantly reduced at each time point after administration (P < 0.01), and the mean arterial pressure was significantly reduced at 6 h (P < 0.05). The arterial blood gas analysis showed that compared with those in the control group, PaO2, PaCO2 and PaO2/FiO2 in the model group were significantly reduced (P < 0.01), and PaO2, PaCO2 and PaO2/FiO2 were significantly increased after caspase inhibitor treatment (P < 0.05 or 0.01). The levels of the inflammatory mediators tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) in the model group were significantly higher than those in the control group (P < 0.01), and they were significantly decreased after caspase inhibitor treatment (P < 0.01). In the model group, pulmonary artery MT, MT% and the degree of muscle vascularization were significantly increased (P < 0.05 or 0.01), and pulmonary artery MT and the degree of muscle vascularization were significantly reduced after caspase inhibitor treatment (P < 0.05 or 0.01). Apoptosis Repressor with a Caspase Recuitment Domain (ARC) can alleviate the occurrence and development of pulmonary hypertension (PH) by affecting hemodynamics and reducing inflammation.

Histomorphometric Study of the Tunics of Ductus Arteriosus in Human Fetal Cadavers Using the ImageJ Software.

The ductus arteriosus (DA) connects the left pulmonary artery with theaorta during fetal life. Although it connects two elastic arteries, histological studies have shown that it is a muscular artery. There are very few studies on the histomorphometry of human fetal cadaveric DA. There are few studies on the changes in the tunics of the DA at various stages of fetal development. The present study aimed to observe the histomorphometric features ofDA and its histological variations according to the gestational age of the fetus. The study sample was DA dissected from 34 fetal cadavers of different gestational ages and stained with standardhematoxylin and eosin staining (H&E). We studied the structure of DA under a light microscope. We used ImageJ software (National Institutes of Health, Bethesda, Maryland) to measure the thickness of all three layers of the DA wall. The thickness of the DA wall was directly proportional to the gestational age of the fetus. In each trimester, we observed distinct histological changes in the tunics. The formation of multiple intimal mounds and the increase in intimal thickness observed during the last trimester are responsible for the closure of the ductus after birth. Elastosis is associated with patent DA. The disappearance of elastosis at a later gestational age ensures the closure of the ductus.

Blunt Trauma Induced Closed Femoral Bone Fracture in a Rat Model: Are Vessels Safe to Use for Microsurgery? Further Insight into the Zone of Injury Concept.

The study aims to investigate the zone of injury for major vessels after high-velocity traumas, as it is unclear whether avoiding vascular structures is necessary during microvascular anastomosis or how long it takes for them to be used again. This study uses Doppler ultrasonography and a rat model to evaluate the histopathological changes and flow velocity of major vessels in the zone of injury after high-velocity trauma with closed femoral bone fracture. Osteosynthesis was performed using an intramedullary wire. Samples were collected from day 3 and week 3. The unaffected contralateral side is used as control. Results from arterial and venous flow assessments showed no evidence of ischemia in the extremities. Both arteries and veins were patent in both intervals and on the control side. The evaluation of the vessels showed arterial injury with a slightly reduced arterial flow on day 3 and week 3. The venous flow was slightly reduced on day 3 but not on week 3. Statistically, arterial endothelial injury was higher on day 3 than on week 3 (p = 0.006). Media inflammation was also higher on day 3 (p = 0.06). Arterial endothelization distribution was higher in week 3 (p = 0.006). No significant differences were found in arterial media irregularity, necrosis, platelet aggregation, bleeding, and wall rupture. Venous samples showed no significant differences in any parameter (p < 0.05). High-velocity trauma increases the risk of thrombosis in vessels. Intravascular repair can start on day 2 and continue till week 3 with significant endothelization. Although physiologic findings do not alter arterial or venous flow, histologic findings support vessel injuries leading to potential complications. Microsurgery should be considered out of the injury zone until adequate vessel healing is achieved.

Sex-biased regulatory changes in the placenta of native highlanders contribute to adaptive fetal development.

Compared with lowlander migrants, native Tibetans have a higher reproductive success at high altitude though the underlying mechanism remains unclear. Here, we compared the transcriptome and histology of full-term placentas between native Tibetans and Han migrants. We found that the placental trophoblast shows the largest expression divergence between Tibetans and Han, and Tibetans show decreased immune response and endoplasmic reticulum stress. Remarkably, we detected a sex-biased expression divergence, where the male-infant placentas show a greater between-population difference than the female-infant placentas. The umbilical cord plays a key role in the sex-biased expression divergence, which is associated with the higher birth weight of the male newborns of Tibetans. We also identified adaptive histological changes in the male-infant placentas of Tibetans, including larger umbilical artery wall and umbilical artery intima and media, and fewer syncytial knots. These findings provide valuable insights into the sex-biased adaptation of human populations, with significant implications for medical and genetic studies of human reproduction.

Solitary pulmonary capillary hemangioma – An underrecognized rare tumor. Report of 32 new cases with literature review

ObjectiveTo explore the clinical, imaging, pathologic characteristics and differential diagnosis of solitary pulmonary capillary hemangioma (SPCH). MethodsThirty two cases of SPCH were collected and studied, with literature review. ResultsThis study included 13 males and 19 females, with a male-to-female ratio of 1:1.5. The age ranged from 26 to 70 years (median age of 43 years). All patients were asymptomatic at presentation. Lung nodules were incidentally discovered during chest computed tomography (CT). Imaging features included 21 cases with partial solid nodules (PSN), 7 cases with ground-glass nodules (GGN), and 4 cases with solid nodules (SN). Eleven cases were in the left lung lower basal segment, 11 cases in the right lung lower basal segment, 6 cases in the right lung upper anterior segment, and 4 cases in the right lung middle lateral segment. The lower basal segments of the lungs were involved in 22 (11 in each lung) cases (22/32, 68 %). The tumors ranged from 6 to 18 mm (average 10 mm). Macroscopically, 16 cases had clear boundaries, while 16 cases had unclear boundaries, and gray-red or dark brown on cut surfaces. Intraoperative frozen section was performed in 27 cases, with diagnosis of SPCH in 12 and pneumonia or inflammatory lesion in 15. Microscopically, the nodules were composed of densely proliferated and dilated capillaries. The capillary walls were lined with a single layer of flat endothelial cells, without atypical features. Collapsed alveolar septa were replaced by a large number of capillaries. All cases showed proliferating capillaries spreading into the walls of small veins/arteries and bronchi, with 3 cases showing dilated capillaries protruding into the bronchiolar lumens as polyp-like structures. Twenty-six cases (26/32, 81 %) showed proliferating capillaries passed over the interlobular septa. Twenty-six cases (26/32, 81 %) showed irregular intimal thickening of small muscular arteries in the peripheral areas of the lesions, with the thickened intima being cellular or fibrous. In twenty-seven cases (27/32, 84 %) the lesions were located in the subpleura, with 6 cases involving the pleura. ConclusionSPCH is a rare benign lung tumor that mostly occurs in the lung lower basal segments with predominance in females. It usually appears as a ground-glass nodule on CT and is very similar to early-stage lung cancer. Accurate diagnosis requires collaboration of radiologists, surgeons, and pathologists. SPCH should be regarded as an important differential diagnosis of small incidental lung nodules.

Az arteria meningea media embolisatio szerepe a krónikus subduralis haematoma kezelési algoritmusában, legújabb evidenciák és saját tapasztalataink

<p>Chronic subdural hematoma is one of the most common diseases requiring a neurosurgical operation that affect elderly and fragile patients. In addition to standard neurosurgical operations (trepanation and craniotomy), embolization of the meningeal artery media is an alternative solution. Several review aerticles have confirmed the very high rate of success and safety of the endovascular treatment. We present the technical details and results of our 10 consecutive selective media meningeal artery embolization procedures for residual chronic subdural hematomas. Our interventions were performed without complications and all resulted in complete recovery.&nbsp;</p>.

Asprosin promotes vascular inflammation via TLR4-NFκB-mediated NLRP3 inflammasome activation in hypertension

Objectiveand design Mild vascular inflammation promotes the pathogenesis of hypertension. Asprosin, a newly discovered adipokine, is closely associated with metabolic diseases. We hypothesized that asprosin might led to vascular inflammation in hypertension via NLRP3 inflammasome formation. This study shows the importance of asprosin in the vascular inflammation of hypertension. MethodsPrimary vascular smooth muscle cells (VSMCs) were obtained from the aorta of animals, including spontaneously hypertensive rats (SHR), Wistar–Kyoto rats (WKY), NLRP3−/− and wild-type mice. Studies were performed in VSMCs in vitro, as well as WKY and SHR in vivo. ResultsAsprosin expressions were up-regulated in VSMCs and media of arteries in SHR. Asprosin overexpression promoted NLRP3 inflammasome activation via Toll-like receptor 4 (TLR4), accompanied with activation of NFκB signaling pathway in VSMCs. Exogenous asprosin protein showed similar roles in promoting NLRP3 inflammasome activation. Knockdown of asprosin restrained NLRP3 inflammasome and p65-NFκB activation in VSMCs of SHR. NLRP3 inhibitor MCC950 or NFκB inhibitor BAY11-7082 attenuated asprosin-caused VSMC proliferation and migration. Asprosin-induced interleukin-1β production, proliferation and migration were attenuated in NLRP3−/− VSMCs. Local asprosin knockdown in common carotid artery of SHR attenuated inflammation and vascular remodeling. ConclusionsAsprosin promoted NLRP3 inflammasome activation in VSMCs by TLR4-NFκB pathway, and thereby stimulates VSMCs proliferation, migration, and vascular remodeling of SHR.

#3001 MtDNA copy number correlates to coronary artery calcium score and biological age in kidney failure patients

Abstract Background and Aims Chronic kidney disease (CKD) and kidney failure are connected to increased oxidative stress and vascular calcification, which are indicators for development of comorbidities and mortality outcome. Mitochondrial (mt)DNA copy number has been reported as independent predictor for frailty and mortality outcome of various cardiovascular diseases (CVD) and cancer. We aimed that mtDNA copy number in whole blood of kidney failure patients can be correlated to coronary artery media calcification score and coronary artery calcium (CAC) score and be used as an independent predictor for comorbidities and mortality outcome. Method Quantitative PCR (qPCR) with TaqMan® probes for three mtDNA genes (mtND1, mtND4 and mtCOX1) and two single locus genes on nuclear DNA (hemoglobin subunit beta and 18S), for normalization, is performed on DNA samples isolated from collected blood of 196 kidney transplant donors and 211 recipients at basal timepoint and 32 at 1-year-follow-up timepoint, included in the KaroKidney biobank. Resulting mtDNA copy number is investigated for correlation to CAC score, patient mortality outcome, biological age determined by skin autofluorescence and other clinical parameters. Results In our Swedish kidney transplant cohort we can see statistically significant difference in mtDNA copy number between kidney failure patients (recipients) and healthy controls (donors). No obvious difference between females and males was observed. mtDNA copy number correlates to biological age determined by skin autofluorescence, CAC score and Framingham CVD risk score. In the 32 1-year-follow-up samples we could see significant increase/recovery of mtDNA copy number for male patients compared to their baseline before receiving a transplant. Conclusion In this study we show that mtDNA copy number in kidney failure patients correlates to biological age and CAC score, affirming mtDNA copy number as an independent predictor of frailty in this Swedish cohort of CKD patients. Additionally, we can see that a kidney transplant can lead to a significant increase of mtDNA copy number in blood one year later, suggesting a general increase in health quality.

Myositis "Diaphragm Cramp" as a Potential Cause of Respiratory Arrests in Infants. Comment on Salfi, N.C.M. et al. Fatal Deterioration of a Respiratory Syncytial Virus Infection in an Infant with Abnormal Muscularization of Intra-Acinar Pulmonary Arteries: Autopsy and Histological Findings. Diagnostics 2024, 14, 601.

This Letter to the Editor provides additional information regarding the tragic case of a 6-month-old in Italy with respiratory syncytial virus who deteriorated and died unexpectedly from rapid respiratory insufficiency [...].

Abstract 146: Phosphodiesterase 10A Mediates Arterial Calcification Through A P38/MAPK-MMP3 Signaling

Background: Vascular calcification is prevalent in patients with atherosclerosis, chronic kidney disease (CKD), diabetes, and peripheral artery disease (PAD). When located in the arterial media, it is strongly associated with increased cardiovascular morbidity and mortality. The cyclic nucleotides cAMP and cGMP play important regulatory roles in a variety of human diseases that are controlled by distinct phosphodiesterase (PDE) isozymes. We have recently found that PDE10A is the most highly induced isoform in a rodent model of arterial calcification. The function and underlying mechanisms of PDE10A in medial artery calcification, however, remain unknown. Methods: Vascular smooth muscle cell (VSMC) calcification was mediated by a high phosphate media. Medial artery calcification was induced by vitamin D 3 injection and 5/6 nephrectomy calcification models. Vascular calcification was assessed by calcium assay and Von Kossa staining. Results: PDE10A was markedly increased in calcifying VSMCs in vitro , calcified arteries in vivo , and calcified human tibial arteries from patients with PAD. Knockdown or inhibition of PDE10A markedly attenuated phosphate-induced VSMC osteogenic transformation and calcification in VSMCs. Conversely, overexpression of PDE10A increased VSMC calcification. Deficiency and inhibition of PDE10A significantly decreased arterial calcification in vivo . Several labs including our own have demonstrated that matrix metallopeptidases (MMPs) are involved in vascular calcification. Using bioinformatics analysis and loss-of-function strategy, we found that MMP-3 could be regulated by PDE10A in calcifying VSMCs. Our further mechanistic studies showed that knockdown or inhibition of PDE10A decreased activated p38 MAPK and that inhibition of p38 MAPK attenuated MMP-3 upregulation under a calcifying condition. These data suggest that PDE10A mediates arterial calcification through a p38 MAPK-MMP-3 signaling pathway. Conclusion: PDE10A is a key regulator in the development of medial artery calcification. Our findings provide insight into the use of PDE10A inhibition strategies to reduce arterial calcification in patients with CKD and PAD.

Optimization of pulmonary artery mechanical testing

Pulmonary arterial hypertension (PAH) is an incurable disease with mortality within 3 years in 28-55% of high-risk patients. The progression of PAH has been known to be associated with increased vascular stiffness and vascular remodeling. Recent studies have suggested that increased stiffness may in fact be a driver for some of the metabolic abnormalities observed during PAH. To gain more insights into this relationship, we need to quantify the differences in mechanical properties of healthy and hypertensive pulmonary arteries. The stress-strain relationship is the gold standard for the ex-vivo stiffness measurement of arteries. This is obtained by obtaining force vs. distension data by tensile testing and using sample dimensions, i.e. length, lumen diameter, and wall thickness, to calculate engineering stress and strain. While this approach is well-optimized for large muscular arteries, it has not been used to test pulmonary arteries as their thin walls and low basal tone make it challenging to make precise measurements of sample wall thickness and lumen diameter. Thus, the goals of this study were to: 1) establish a reliable protocol for rat pulmonary artery tensile testing and 2) quantify the differences in stiffness between hypertensive and healthy pulmonary arteries. First, a methodology to improve the fidelity of determining the lumen diameter and wall thickness was developed. Using this approach, we observed that the modulus was negatively correlated with the length of the vessel segment tested. This suggests that vessel length should be standardized to perform reliable comparisons between groups. Next, we performed tensile tensing on both control and hypertensive pulmonary arteries, after standardizing vessel segment lengths. We initially modeled this tensile testing data using a one-term exponential equation and we observed that intact hypertensive arteries were ~2.7 times stiffer than control arteries at low strain (strain = 0.8). Whereas at high strain (strain = 2.8) intact and decellularized hypertensive arteries were 20 and 29 times stiffer than control arteries respectively. To better capture the viscoelastic properties of both, the cellular and ECM components of the vessels we also fit the tensile testing data using a two-term exponential equation. Using this two-term exponential model, we observed that hypertensive vessels were 2.2 times stiffer than the controls at normal hoop stress (20 kPa), and at the hypertensive hoop stress (66 kPa) the diseased vessels showed less variability in stiffness as compared to the controls. These findings and the methods developed in this study will be helpful in conducting and analyzing experiments to investigate the relationship between changes in biomechanical signals and the progression of PAH. R01HL151530 (KS), R01HL126514 (LS). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.