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Integrative Medicine (Encinitas, Calif.) Jan 2024We report on 6 patients in our care who were harboring atherosclerotic plaque in the carotid arteries. This condition poses a risk of acute ischemic stroke and indicates...
We report on 6 patients in our care who were harboring atherosclerotic plaque in the carotid arteries. This condition poses a risk of acute ischemic stroke and indicates potential atherosclerosis elsewhere in the vascular system. The plaque was revealed by routine ultrasound measurement of carotid intima-medial thickness (CIMT) defined as the distance between the lumen-intima interface and the media-adventitia interface. Recent improvements in image resolution and edge detection algorithms have resulted in improved reliability and clinical usefulness of the technology. The patients were enrolled in a systems-based functional medicine program of cardiology prevention to address root causes. The program provided personalized interventions that included drug therapy, dietary supplements, and lifestyle modification. The 6 patients followed the integrative regimen, which successfully managed existing cardiovascular symptoms and risk factors while keeping various biomarkers under control. However, they continued to exhibit carotid plaque with no improvement. A novel dietary supplement that targets endothelial glycocalyx regeneration was added to the personalized intervention programs. The supplement contains a proprietary extract of rhamnan sulfate from the green seaweed The 6 participants consumed the supplement daily, and their plaque burden was measured after 6 months using the same CIMT technology. In every case, the total plaque burden was reduced, with an average reduction in the 6 patients of 5.55 mm, which is statistically significant. Significant reductions in maximum carotid plaque thickness were also observed at the end of the 6 months. The study suggests that rhamnan sulfate from may provide a safe and effective intervention for reducing atherosclerotic plaque, and should be evaluated as an adjunct therapy for prevention and treatment of cardiovascular disease.
PubMed: 38404609
DOI: No ID Found -
Journal of Clinical Medicine Feb 2024We have previously reported that endothelial-to-mesenchymal transition (EndMT) is an active process in patients with idiopathic pulmonary fibrosis (IPF) contributing to...
TGF-β1, pSmad-2/3, Smad-7, and β-Catenin Are Augmented in the Pulmonary Arteries from Patients with Idiopathic Pulmonary Fibrosis (IPF): Role in Driving Endothelial-to-Mesenchymal Transition (EndMT).
We have previously reported that endothelial-to-mesenchymal transition (EndMT) is an active process in patients with idiopathic pulmonary fibrosis (IPF) contributing to arterial remodelling. Here, we aim to quantify drivers of EndMT in IPF patients compared to normal controls (NCs). Lung resections from thirteen IPF patients and eleven NCs were immunohistochemically stained for EndMT drivers, including TGF-β1, pSmad-2/3, Smad-7, and β-catenin. Intima, media, and adventitia were analysed for expression of each EndMT driver in pulmonary arteries. Computer- and microscope-assisted Image ProPlus7.0 image analysis software was used for quantifications. Significant TGF-β1, pSmad-2/3, Smad-7, and β-catenin expression was apparent across all arterial sizes in IPF ( < 0.05). Intimal TGF-β1, pSmad-2/3, Smad-7, and β-catenin were augmented in the arterial range of 100-1000 μm ( < 0.001) compared to NC. Intimal TGF-β1 and β-catenin percentage expression showed a strong correlation with the percentage expression of intimal vimentin (r' = 0.54, = 0.05 and r' = 0.61, = 0.02, respectively) and intimal N-cadherin (r' = 0.62, = 0.03 and r' = 0.70, = 0.001, respectively). Intimal TGF-β1 and β-catenin expression were significantly correlated with increased intimal thickness as well (r' = 0.52, = 0.04; r' = 0.052, = 0.04, respectively). Moreover, intimal TGF-β1 expression was also significantly associated with increased intimal elastin deposition (r' = 0.79, = 0.002). Furthermore, total TGF-β1 expression significantly impacted the percentage of DLCO (r' = -0.61, = 0.03). This is the first study to illustrate the involvement of active TGF-β/Smad-2/3-dependent and β-catenin-dependent Wnt signalling pathways in driving EndMT and resultant pulmonary arterial remodelling in patients with IPF. EndMT is a potential therapeutic target for vascular remodelling and fibrosis in general in patients with IPF.
PubMed: 38398472
DOI: 10.3390/jcm13041160 -
Journal of Laparoendoscopic & Advanced... Apr 2024Esophageal submucosal tumors (SMTs) are rare, occurring in less than 1% of esophageal neoplasms. For surgical treatment of esophageal SMTs, enucleation is usually the...
Esophageal submucosal tumors (SMTs) are rare, occurring in less than 1% of esophageal neoplasms. For surgical treatment of esophageal SMTs, enucleation is usually the procedure of choice for benign tumors. This study aimed at evaluating the surgical technique and outcomes of thoracoscopic enucleation with esophagoscopy for esophageal SMTs. Patients with esophageal SMTs who underwent thoracoscopic enucleation between 2015 and 2022 were retrospectively investigated. Surgery was performed with the patient in the prone position. First, an esophagoscope was inserted, and a sodium hyaluronate solution with indigo carmine dye was injected into the submucosal layer just below the tumor. Next, under thoracoscopy, the tumor was exposed through a thoracoscopic incision and dissection of the muscularis propria and adventitia was performed at the tumor site. The colored layer resulting from the previously injected dye was identified, and tumor enucleation was performed under guidance of the dye so as not to damage the mucosa or pseudocapsule. In total, 5 surgeries were performed. The mean operative time was 122.6 minutes (range 84-168 minutes), mean blood loss was 21.1 mL (range 0-80 mL), and mean postoperative hospital stay was 8 days (range 7-10 days). There were no postoperative complications. Pathological diagnosis revealed 2 cases of gastrointestinal stromal tumors, 2 cases of schwannoma, and 1 case of leiomyoma. We believe that this technique is a useful and safe method of performing thoracoscopic enucleation of esophageal SMTs because the injected dye provides an indicator of the resection line during enucleation.
Topics: Humans; Esophagoscopy; Prone Position; Retrospective Studies; Esophageal Neoplasms; Thoracoscopy; Treatment Outcome
PubMed: 38359395
DOI: 10.1089/lap.2023.0466 -
Cardiovascular Pathology : the Official... 2024The telocyte (TC) is a new interstitial cell type described in a wide variety of organs and loose connective tissues around small vessels, but its presence in large...
The telocyte (TC) is a new interstitial cell type described in a wide variety of organs and loose connective tissues around small vessels, but its presence in large arteries remains unexplored. TCs have small cell bodies and remarkably thin, long, moniliform processes called telopods (Tps). Using transmission electron microscopy and immunofluorescence, we identified TCs in normal human thoracic aortas and in those with aneurysm or acute dissection (TAAD). In normal aortas the TCs were distributed throughout the connective tissue of the adventitial layer, in its innermost portion and at the zone of transition with the medial layer, with their long axes oriented parallel to the external elastic lamellae, forming a three-dimensional network, without prevalence in the media layer. In contrast, TAAD TCs were present in the medial layer and in regions of neovascularization. The most important feature of the adventitia of diseased aortas was the presence of numerous contacts between TCs and stem cells, including vascular progenitor cells. Although the biologically functional correlations need to be elucidated, the morphological observations presented here provide strong evidence of the involvement of TCs in maintaining vascular homeostasis in pathological situations of tissue injury.
Topics: Humans; Telocytes; Homeostasis; Aortic Dissection; Aorta, Thoracic; Male; Microscopy, Electron, Transmission; Middle Aged; Aged; Adventitia; Aortic Aneurysm, Thoracic; Female; Telopodes; Adult; Fluorescent Antibody Technique; Case-Control Studies
PubMed: 38309490
DOI: 10.1016/j.carpath.2024.107617 -
Using Neuroimaging to Study Cerebral Amyloid Angiopathy and Its Relationship to Alzheimer's Disease.Journal of Alzheimer's Disease : JAD 2024Cerebral amyloid angiopathy (CAA) is characterized by amyloid-β aggregation in the media and adventitia of the leptomeningeal and cortical blood vessels. CAA is one of... (Review)
Review
Cerebral amyloid angiopathy (CAA) is characterized by amyloid-β aggregation in the media and adventitia of the leptomeningeal and cortical blood vessels. CAA is one of the strongest vascular contributors to Alzheimer's disease (AD). It frequently co-occurs in AD patients, but the relationship between CAA and AD is incompletely understood. CAA may drive AD risk through damage to the neurovascular unit and accelerate parenchymal amyloid and tau deposition. Conversely, early AD may also drive CAA through cerebrovascular remodeling that impairs blood vessels from clearing amyloid-β. Sole reliance on autopsy examination to study CAA limits researchers' ability to investigate CAA's natural disease course and the effect of CAA on cognitive decline. Neuroimaging allows for in vivo assessment of brain function and structure and can be leveraged to investigate CAA staging and explore its associations with AD. In this review, we will discuss neuroimaging modalities that can be used to investigate markers associated with CAA that may impact AD vulnerability including hemorrhages and microbleeds, blood-brain barrier permeability disruption, reduced cerebral blood flow, amyloid and tau accumulation, white matter tract disruption, reduced cerebrovascular reactivity, and lowered brain glucose metabolism. We present possible areas for research inquiry to advance biomarker discovery and improve diagnostics.
Topics: Humans; Alzheimer Disease; Cerebral Amyloid Angiopathy; Brain; Amyloid beta-Peptides; Neuroimaging; Amyloid; Amyloidogenic Proteins
PubMed: 38306032
DOI: 10.3233/JAD-230553 -
Arteriosclerosis, Thrombosis, and... Mar 2024The metabolic alterations occurring within the arterial architecture during atherosclerosis development remain poorly understood, let alone those particular to each... (Observational Study)
Observational Study
BACKGROUND
The metabolic alterations occurring within the arterial architecture during atherosclerosis development remain poorly understood, let alone those particular to each arterial tunica. We aimed first to identify, in a spatially resolved manner, the specific metabolic changes in plaque, media, adventitia, and cardiac tissue between control and atherosclerotic murine aortas. Second, we assessed their translatability to human tissue and plasma for cardiovascular risk estimation.
METHODS
In this observational study, mass spectrometry imaging (MSI) was applied to identify region-specific metabolic differences between atherosclerotic (n=11) and control (n=11) aortas from low-density lipoprotein receptor-deficient mice, via histology-guided virtual microdissection. Early and advanced plaques were compared within the same atherosclerotic animals. Progression metabolites were further analyzed by MSI in 9 human atherosclerotic carotids and by targeted mass spectrometry in human plasma from subjects with elective coronary artery bypass grafting (cardiovascular risk group, n=27) and a control group (n=27).
RESULTS
MSI identified 362 local metabolic alterations in atherosclerotic mice (log2 fold-change ≥1.5; ≤0.05). The lipid composition of cardiac tissue is altered during atherosclerosis development and presents a generalized accumulation of glycerophospholipids, except for lysolipids. Lysolipids (among other glycerophospholipids) were found at elevated levels in all 3 arterial layers of atherosclerotic aortas. LPC(18:0) (lysophosphatidylcholine; =0.024) and LPA(18:1) (lysophosphatidic acid; =0.025) were found to be significantly elevated in advanced plaques as compared with mouse-matched early plaques. Higher levels of both lipid species were also observed in fibrosis-rich areas of advanced- versus early-stage human samples. They were found to be significantly reduced in human plasma from subjects with elective coronary artery bypass grafting (<0.001 and =0.031, respectively), with LPC(18:0) showing significant association with cardiovascular risk (odds ratio, 0.479 [95% CI, 0.225-0.883]; =0.032) and diagnostic potential (area under the curve, 0.778 [95% CI, 0.638-0.917]).
CONCLUSIONS
An altered phospholipid metabolism occurs in atherosclerosis, affecting both the aorta and the adjacent heart tissue. Plaque-progression lipids LPC(18:0) and LPA(18:1), as identified by MSI on tissue, reflect cardiovascular risk in human plasma.
Topics: Humans; Animals; Mice; Plaque, Atherosclerotic; Cardiovascular Diseases; Risk Factors; Atherosclerosis; Aorta; Aortic Diseases; Glycerophospholipids; Heart Disease Risk Factors
PubMed: 38299357
DOI: 10.1161/ATVBAHA.123.320278 -
Journal of Cellular Physiology Apr 2024Vascular smooth muscle cells (VSMCs) play a critical role in regulating vasotone, and their phenotypic plasticity is a key contributor to the pathogenesis of various... (Review)
Review
Vascular smooth muscle cells (VSMCs) play a critical role in regulating vasotone, and their phenotypic plasticity is a key contributor to the pathogenesis of various vascular diseases. Two main VSMC phenotypes have been well described: contractile and synthetic. Contractile VSMCs are typically found in the tunica media of the vessel wall, and are responsible for regulating vascular tone and diameter. Synthetic VSMCs, on the other hand, are typically found in the tunica intima and adventitia, and are involved in vascular repair and remodeling. Switching between contractile and synthetic phenotypes occurs in response to various insults and stimuli, such as injury or inflammation, and this allows VSMCs to adapt to changing environmental cues and regulate vascular tone, growth, and repair. Furthermore, VSMCs can also switch to osteoblast-like and chondrocyte-like cell phenotypes, which may contribute to vascular calcification and other pathological processes like the formation of atherosclerotic plaques. This provides discusses the mechanisms that regulate VSMC phenotypic switching and its role in the development of vascular diseases. A better understanding of these processes is essential for the development of effective diagnostic and therapeutic strategies.
Topics: Humans; Aortic Dissection; Atherosclerosis; Cell Proliferation; Cells, Cultured; Hypertension; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Phenotype
PubMed: 38291732
DOI: 10.1002/jcp.31200 -
International Journal of Pediatric... Feb 2024Vocal cord paralysis has been reported as a common complication of button battery (BB) ingestion, and there is a need to confirm the mechanism of vocal cord paralysis...
PURPOSE
Vocal cord paralysis has been reported as a common complication of button battery (BB) ingestion, and there is a need to confirm the mechanism of vocal cord paralysis for the development of a standardized treatment.
METHODS
A new CR2032 BB and artificial saliva were placed in a fresh pig esophagus with the recurrent laryngeal nerve (RLN); the negative electrode faced the nerve in the experimental group, while the positive electrode faced the nerve in the control group. The pH values of the intra- and extraesophageal walls were measured simultaneously. Pathological examination was performed after the esophagus and nerves were damaged.
RESULTS
After BB ingestion, the pH near the intraesophageal negative electrode increased rapidly, reaching 11.5 at 30 min and over 14 at 6 h, while the extraesophageal pH did not change at 1 h and began to accelerate after 2 h, reaching 10 at 6 h. After 6 h of exposure, the pathological section showed that the structure of the mucosa, submucosa, and muscle layer were destroyed; chromatin in the nucleus faded, and part of the nerve bundle in the adventitia had liquefaction necrosis.
CONCLUSION
The basic mechanism of vocal cord paralysis caused by BB ingestion is that the OH generated by the electrolytic reaction of the negative electrode penetrates the esophageal wall and corrodes the RLN, which may be the cause of vocal cord paralysis caused by BB ingestion without esophageal perforation.
Topics: Child; Humans; Animals; Swine; Vocal Cord Paralysis; Esophagus; Electric Power Supplies; Necrosis; Recurrent Laryngeal Nerve; Eating
PubMed: 38286078
DOI: 10.1016/j.ijporl.2024.111872 -
Journal of Clinical Medicine Jan 2024The abdominal aortic aneurysm (AAA) is defined as an increase in aortic diameter by more than 50% and is associated with a high risk of rupture and mortality without...
BACKGROUND
The abdominal aortic aneurysm (AAA) is defined as an increase in aortic diameter by more than 50% and is associated with a high risk of rupture and mortality without treatment. The aim of this study is to analyze the role of aortic adventitial collagen photocrosslinking by UV-A irradiation on the biomechanical profile of the aortic wall.
METHODS
This experimental study is structured in two parts: the first part includes in vitro uniaxial biomechanical evaluation of porcine adventitial tissue subjected to either short-term elastolysis or long-term collagenolysis in an attempt to duplicate two extreme situations as putative stages of aneurysmal degeneration. In the second part, we included biaxial biomechanical evaluation of in vitro human abdominal aortic adventitia and human AAA adventitia specimens. Biomechanical profiles were examined for porcine and human aortic tissue before and after irradiation with UV-A light (365 nm wavelength).
RESULTS
On the porcine aortic sample, the enhancing effect of irradiation was evident both on the tissue subjected to elastolysis, which had a high collagen-to-elastin ratio, and on the tissue subjected to prolonged collagenolysis despite being considerably depleted in collagen. Further, the effect of irradiation was conclusively demonstrated in the human adventitia samples, where significant post-irradiation increases in Cauchy stress (longitudinal axis: = 0.001, circumferential axis: = 0.004) and Young's modulus (longitudinal axis: = 0.03, circumferential axis: = 0.004) were recorded. Moreover, we have a stronger increase in the strengthening of the AAA adventitia samples following the exposure to UV-A irradiation ( = 0.007) and a statistically significant but not very important increase ( = 0.021) regarding the stiffness in the circumferential axis.
CONCLUSIONS
The favorable effect of UV irradiation on the strength and stiffness of degraded aortic adventitia in experimental situations mimicking early and later stages of aneurysmal degeneration is essential for the development and potential success of procedures to prevent aneurysmal ruptures. The experiments on human normal and aneurysmal adventitial tissue confirmed the validity and potential success of a procedure based on exposure to UV-A radiation.
PubMed: 38276139
DOI: 10.3390/jcm13020633 -
Journal of Cellular Physiology Apr 2024Carotid body tumor (CBT) is a rare neck tumor located at the adventitia of the common carotid artery bifurcation. The prominent pathological features of CBT are high...
Carotid body tumor (CBT) is a rare neck tumor located at the adventitia of the common carotid artery bifurcation. The prominent pathological features of CBT are high vascularization and abnormal proliferation. However, single-cell transcriptome analysis of the microenvironment composition and molecular complexity in CBT has yet to be performed. In this study, we performed single-cell RNA sequencing (scRNA-seq) analysis on human CBT to define the cells that contribute to hypervascularization and chronic hyperplasia. Unbiased clustering analysis of transcriptional profiles identified 16 distinct cell populations including endothelial cells (ECs), smooth muscle cells (SMCs), neuron cells, macrophage cells, neutrophil cells, and T cells. Within the ECs population, we defined subsets with angiogenic capacity plus clear signs of later endothelial progenitor cells (EPCs) to normal ECs. Two populations of macrophages were detectable in CBT, macrophage1 showed enrichment in hypoxia-inducible factor-1 (HIF-1) and as well as an early EPCs cell-like population expressing CD14 and vascular endothelial growth factor. In addition to HIF-1-related transcriptional protein expression, macrophages1 also display a neovasculogenesis-promoting phenotype. SMCs included three populations showing platelet-derived growth factor receptor beta and vimentin expression, indicative of a cancer-associated fibroblast phenotype. Finally, we identified three types of neuronal cells, including chief cells and sustentacular cells, and elucidated their distinct roles in the pathogenesis of CBT and abnormal proliferation of tumors. Overall, our study provided the first comprehensive characterization of the transcriptional landscape of CBT at scRNA-seq profiles, providing novel insights into the mechanisms underlying its formation.
Topics: Humans; Carotid Arteries; Carotid Body Tumor; Endothelial Progenitor Cells; Single-Cell Analysis; Single-Cell Gene Expression Analysis; Transcriptome; Tumor Microenvironment; Vascular Endothelial Growth Factor A; Neovascularization, Pathologic
PubMed: 38214142
DOI: 10.1002/jcp.31175