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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 -
JVS-vascular Science 2023Synchrotron radiation-based X ray phase-contrast tomography (XPCT) was used in this study to evaluate abdominal aorta specimens from patients with sac expansion without...
OBJECTIVE
Synchrotron radiation-based X ray phase-contrast tomography (XPCT) was used in this study to evaluate abdominal aorta specimens from patients with sac expansion without evidence of an endoleak (endotension) following endovascular aortic repair (EVAR) for an abdominal aortic aneurysm (AAA). The aim of this study was to analyze the morphologic structure of the aortic wall in patients with this condition and to establish the cause of the endotension.
METHODS
Human aortic specimens of the abdominal aorta were obtained during open repair, fixed with formalin, and analyzed among three groups. Group A was specimens from open abdominal aortic aneurysm repairs (n = 7). Group E was specimens from sac expansion without an evident endoleak after EVAR (n = 7). Group N was specimens from non-aneurysmal "normal" cadaveric abdominal aortas (n = 5). Using XPCT (effective voxel size, 12.5 μm; density resolution, 1 mg/cm), we measured the density of the tunica media (TM) in six regions of each sample. Then, any changes to the elastic lamina and the vasa vasorum were analyzed pathologically. The specimens were immunohistochemically examined with anti-CD31 and vascular endothelial growth factor antibodies.
RESULTS
The time from EVAR to open aortic repair was 64.2 ± 7.2 months. There were significant differences in the thickness of the TM among three groups: 0.98 ± 0.03 mm in Group N; 0.31 ± 0.01 mm in Group A; and 0.15 ± 0.03 mm in Group E ( < .005). There were significant differences in the TM density among the groups: 1.087 ± 0.004 g/cm in Group N; 1.070 ± 0.001 g/cm in Group A; and 1.062 ± 0.007 g/cm in Group E ( < .005). Differences in the thickness and density of the TM correlated with the thickness of the elastic lamina; in Group N, uniform high-density elastic fibers were observed in the TM. By contrast, a thinning of the elastic lamina in the TM was observed in Group A. A marked thinness and loss of elastic fibers was observed in Group E. CD31 immunostaining revealed that the vasa vasorum was localized in the adventitia and inside the outer third of the TM in Group N, and in the middle of the TM in Group A. In Group E, the vasa vasorum advanced up to the intima with vascular endothelial growth factor-positive cells in the intimal section.
CONCLUSIONS
XPCT could be used to demonstrate the densitometric property of the aortic aneurysmal wall after EVAR. We confirmed that the deformation process that occurs in the sac expansion after EVAR without evidence of an endoleak could be explained by hypoxia in the aortic wall.
PubMed: 37662587
DOI: 10.1016/j.jvssci.2023.100123 -
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 -
Bioengineering (Basel, Switzerland) Oct 2023Automated segmentation of carotid lumen-intima boundary (LIB) and media-adventitia boundary (MAB) by deep convolutional neural networks (CNN) from three-dimensional...
Development of a Three-Dimensional Carotid Ultrasound Image Segmentation Workflow for Improved Efficiency, Reproducibility and Accuracy in Measuring Vessel Wall and Plaque Volume and Thickness.
Automated segmentation of carotid lumen-intima boundary (LIB) and media-adventitia boundary (MAB) by deep convolutional neural networks (CNN) from three-dimensional ultrasound (3DUS) images has made assessment and monitoring of carotid atherosclerosis more efficient than manual segmentation. However, training of CNN still requires manual segmentation of LIB and MAB. Therefore, there is a need to improve the efficiency of manual segmentation and develop strategies to improve segmentation accuracy by the CNN for serial monitoring of carotid atherosclerosis. One strategy to reduce segmentation time is to increase the interslice distance (ISD) between segmented axial slices of a 3DUS image while maintaining the segmentation reliability. We, for the first time, investigated the effect of ISD on the reproducibility of MAB and LIB segmentations. The intra-observer reproducibility of LIB and MAB segmentations at ISDs of 1 mm and 2 mm was not statistically significantly different, whereas the reproducibility at ISD = 3 mm was statistically lower. Therefore, we conclude that segmentation with an ISD of 2 mm provides sufficient reliability for CNN training. We further proposed training the CNN by the baseline images of the entire cohort of patients for automatic segmentation of the follow-up images acquired for the same cohort. We validated that segmentation with this time-based partitioning approach is more accurate than that produced by patient-based partitioning, especially at the carotid bifurcation. This study forms the basis for an efficient, reproducible, and accurate 3DUS workflow for serial monitoring of carotid atherosclerosis useful in risk stratification of cardiovascular events and in evaluating the efficacy of new treatments.
PubMed: 37892947
DOI: 10.3390/bioengineering10101217 -
Neurology India 2023Knot configuration is an important but relatively neglected topic in microvascular anastomosis literature.
BACKGROUND
Knot configuration is an important but relatively neglected topic in microvascular anastomosis literature.
OBJECTIVE
To study the differences between end-to-end microvascular anastomosis performed with two-throw reef knots as compared to traditional three-throw knots in a rat femoral artery model at the histological level.
MATERIAL AND METHODS
Sprague Dawley rats underwent end-to-end microvascular anastomosis of the right femoral artery (one-way-up method). The rats were divided into two groups: two-throw reef knots versus traditional three-throw knots. The patency was checked by the standard empty refill method. After 2 weeks, the rats underwent re-exploration. An anastomotic segment was sent for histological analysis. Histological alterations including luminal patency and changes in Tunica intima, Tunica media, and Tunica adventitia were compared between the two groups.
RESULTS
Twenty-nine rats were operated on by the senior author (17 by three-throw and 12 by two-throw reef knots). In the two-throw reef knot group versus the traditional three-throw knot group, the immediate patency rates were 100% versus 82.4%, and the delayed patency rates were 90.9% versus 62.5%, respectively. The histopathological patency rates were concordant with delayed patency rates. Subintimal proliferation and fibrosis were comparable in both groups. Adventitial granulomas were noted in all, irrespective of the knotting technique. Tunica media preservation rates for the two-throw reef knot versus the traditional three-throw knot group were 63.6% versus 0%. Five rats were operated by the beginner in the field, all by two-throw reef knots (to assess the safety of this new method in the hands of a beginner).
CONCLUSION
Microvascular anastomosis performed with two-throw reef knots appears not only feasible but better in terms of anastomosis patency. Histological superiority in terms of Tunica media preservation further validates the technique.
Topics: Rats; Animals; Rats, Sprague-Dawley; Suture Techniques; Anastomosis, Surgical; Femoral Artery
PubMed: 38174453
DOI: 10.4103/0028-3886.391390 -
Archives of Plastic Surgery Nov 2023In recent decades, a number of simulation models for microsurgical training have been published. The human placenta has received extensive validation in...
In recent decades, a number of simulation models for microsurgical training have been published. The human placenta has received extensive validation in microneurosurgery and is a useful instrument to facilitate learning in microvascular repair techniques as an alternative to using live animals. This study uses a straightforward, step-by-step procedure for instructing the creation of simulators with dynamic flow to characterize the placental vascular tree and assess its relevance for plastic surgery departments. Measurements of the placental vasculature and morphological characterization of 18 placentas were made. After the model was used in a basic microsurgery training laboratory session, a survey was given to nine plastic surgery residents, two microsurgeons, and one hand surgeon. In all divisions, venous diameters were larger than arterial diameters, with minimum diameters of 0.8 and 0.6 mm, respectively. The majority of the participants considered that the model faithfully reproduces a real microsurgical scenario; the consistency of the vessels and their dissection are similar in in vivo tissue. Furthermore, all the participants considered that this model could improve their surgical technique and would propose it for microsurgical training. As some of the model's disadvantages, an abundantly thick adventitia, a thin tunica media, and higher adherence to the underlying tissue were identified. The color-perfused placenta is an excellent tool for microsurgical training in plastic surgery. It can faithfully reproduce a microsurgical scenario, offering an abundance of vasculature with varying sizes similar to tissue in vivo, enhancing technical proficiency, and lowering patient error.
PubMed: 38143834
DOI: 10.1055/a-2113-4182 -
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 -
World Journal of Clinical Cases Nov 2023Transcutaneous oxygen pressure (TcpO) is a precise method for determining oxygen perfusion in wounded tissues. The device uses either electrochemical or optical sensors.
BACKGROUND
Transcutaneous oxygen pressure (TcpO) is a precise method for determining oxygen perfusion in wounded tissues. The device uses either electrochemical or optical sensors.
AIM
To evaluate the usefulness of TcpO measurements on free flaps (FFs) in diabetic foot ulcers (DFUs).
METHODS
TcpO was measured in 17 patients with DFUs who underwent anterolateral thigh (ALT)-FF surgery and compared with 30 patients with DFU without FF surgery.
RESULTS
Significant differences were observed in the ankle-brachial index; duration of diabetes; and haemoglobin, creatinine, and C-reactive protein levels between the two groups. TcpO values were similar between two groups except on postoperative days 30 and 60 when the values in the ALT-FF group remained < 30 mmHg and did not increase > 50 mmHg.
CONCLUSION
Even if the flap is clinically stable, sympathectomy due to adventitia stripping during anastomosis and arteriovenous shunt progression due to diabetic polyneuropathy could lead to low TcpO values in the ALT-FF owing to its thick fat tissues, which is supported by the slow recovery of the sympathetic tone following FF. Therefore, TcpO measurements in patients with DFU who underwent FF reconstruction may be less accurate than in those who did not.
PubMed: 38078127
DOI: 10.12998/wjcc.v11.i31.7570 -
Lipids in Health and Disease Jul 2023Thermoxidation of edible oil through deep fat frying results in the generation of several oxidized products that promote lipid peroxidation and ROS production when...
Oxidized dietary lipids induce vascular inflammation and atherogenesis in post-menopausal rats: estradiol and selected antihyperlipidemic drugs restore vascular health in vivo.
BACKGROUND
Thermoxidation of edible oil through deep fat frying results in the generation of several oxidized products that promote lipid peroxidation and ROS production when eaten. Consumption of thermoxidized oil in post-menopausal conditions where the estrogen level is low contributes to cardiovascular disease. This study evaluates the role of estradiol and antihyperlipidemic agents (AHD) in restoring the vascular health of ovariectomized (OVX) rats fed with thermoxidized palm oil (TPO) and thermoxidized soya oil (TSO) diets.
METHOD
A total of 10 groups of rats (n = 6) were set up for the experiment. Group I (normal control) rats were sham handled while other groups were OVX to bring about estrogen deficient post-menopausal state. Group II (OVX only) was not treated and received normal rat chow. Groups III-X were fed with either TPO or TSO diet for 12 weeks and treated with estradiol (ETD) 0.2 mg/kg/day, atorvastatin (ATV) 10 mg/kg/day, and a fixed-dose combination of ezetimibe and ATV (EZE 3 mg/kg/day + ATV 10 mg/kg/day).
RESULTS
Pro-atherogenic lipids levels were significantly elevated in untreated TSO and TPO groups compared to OVX and sham, resulting in increased atherogenic and Coronary-risk indices. Treatment with Estradiol and AHDs significantly reduced the total cholesterol, triglycerides, low-density lipoprotein cholesterol as well as AI and CRI compared to untreated TSO and TPO groups, whereas TSO and TPO groups showed significant elevation in these parameters compared to Group I values. Moreover, aortic TNF-α levels were extremely elevated in the untreated TSO and TPO compared to Group I. TNF-α levels were significantly reduced in rats treated with AHDs and ETD. Localized oxidative stress was indicated in the aortic tissues of TSO and TPO-fed OVX rats by increased malondialdehyde and decreased glutathione, catalase, and superoxide dismutase levels. This contributed to a depletion in aortic nitric oxide. AHDs and ETD replenished the nitric oxide levels significantly. Histological evaluation of the aorta of TSO and TPO rats revealed increased peri-adventitia fat, aortic medial hypertrophy, and aortic recanalization. These pathologic changes were less seen in AHDs and ETD rats.
CONCLUSION
This study suggests that ETD and AHDs profoundly attenuate oxidized lipid-induced vascular inflammation and atherogenesis through oxidative-stress reduction and inhibition of TNF-α signaling.
Topics: Rats; Animals; Female; Humans; Estradiol; Nitric Oxide; Postmenopause; Tumor Necrosis Factor-alpha; Lipids; Hypolipidemic Agents; Diet; Atorvastatin; Cholesterol; Estrogens; Atherosclerosis; Inflammation; Ovariectomy
PubMed: 37495992
DOI: 10.1186/s12944-023-01818-y -
Frontiers in Physiology 2024Redox processes can modulate vascular pathophysiology. The endoplasmic reticulum redox chaperone protein disulfide isomerase A1 (PDIA1) is overexpressed during vascular...
Redox processes can modulate vascular pathophysiology. The endoplasmic reticulum redox chaperone protein disulfide isomerase A1 (PDIA1) is overexpressed during vascular proliferative diseases, regulating thrombus formation, endoplasmic reticulum stress adaptation, and structural remodeling. However, both protective and deleterious vascular effects have been reported for PDIA1, depending on the cell type and underlying vascular condition. Further understanding of this question is hampered by the poorly studied mechanisms underlying PDIA1 expression regulation. Here, we showed that PDIA1 mRNA and protein levels were upregulated (average 5-fold) in the intima and media/adventitia following partial carotid ligation (PCL). Our search identified that miR-204-5p and miR-211-5p (miR-204/211), two broadly conserved miRNAs, share PDIA1 as a potential target. MiR-204/211 was downregulated in vascular layers following PCL. In isolated endothelial cells, gain-of-function experiments of miR-204 with miR mimic decreased PDIA1 mRNA while having negligible effects on markers of endothelial activation/stress response. Similar effects were observed in vascular smooth muscle cells (VSMCs). Furthermore, PDIA1 downregulation by miR-204 decreased levels of the VSMC contractile differentiation markers. In addition, PDIA1 overexpression prevented VSMC dedifferentiation by miR-204. Collectively, we report a new mechanism for PDIA1 regulation through miR-204 and identify its relevance in a model of vascular disease playing a role in VSMC differentiation. This mechanism may be regulated in distinct stages of atherosclerosis and provide a potential therapeutic target.
PubMed: 38638277
DOI: 10.3389/fphys.2024.1327794