Microplastics in three types of human arteries detected by pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS).

Microplastics are ubiquitous in the environment. Human body can be exposed to microplastics through inhalation and ingestion and some microplastics can enter the blood and accumulate in various tissues and organs throughout the body. Animal experiments have suggested that microplastics may promote atherosclerosis. However, data on microplastics in human arteries and clinical evidence supporting a link between microplastics and atherosclerosis are currently lacking. Pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS) was used in this study to detect microplastics in three types of human arteries: coronary and carotid arteries with atherosclerotic plaques, as well as the aorta without plaques. Microplastics were detected in all 17 arterial samples, with an average concentration of 118.66 ± 53.87 µg/g tissue. Four types of microplastics were identified: polyethylene terephthalate (PET, 73.70%), polyamide-66 (PA-66, 15.54%), polyvinyl chloride (PVC, 9.69%), and polyethylene (PE, 1.07%). Most importantly, the concentration of microplastics in arteries containing atherosclerotic plaques, both coronary arteries (156.50 ± 42.14 vs. 76.26 ± 14.86 µg/g tissue, P = 0.039), and carotid arteries (133.37 ± 60.52 vs. 76.26 ± 14.86 µg/g tissue, P = 0.015), was significantly higher than that in aortas which did not contain atherosclerotic plaques, suggesting that microplastics might be associated with atherosclerosis in humans. This study provides valuable data for further hazard assessments of microplastics on human cardiovascular health.

Orosomucoid 2 as a biomarker of carotid artery atherosclerosis plaque vulnerability through its generation of reactive oxygen species and lipid accumulation in vascular smooth muscle cells.

BACKGROUND: Orosomucoid (ORM) has been reported as a biomarker of carotid atherosclerosis, but the role of ORM 2, a subtype of ORM, in carotid atherosclerotic plaque formation and the underlying mechanism have not been established. METHODS: Plasma was collected from patients with carotid artery stenosis (CAS) and healthy participants and assessed using mass spectrometry coupled with isobaric tags for relative and absolute quantification (iTRAQ) technology to identify differentially expressed proteins. The key proteins and related pathways were identified via western blotting, immunohistochemistry, and polymerase chain reaction of carotid artery plaque tissues and in vitro experiments involving vascular smooth muscle cells (VSMCs). RESULTS: We screened 33 differentially expressed proteins out of 535 proteins in the plasma. Seventeen proteins showed increased expressions in the CAS groups relative to the healthy groups, while 16 proteins showed decreased expressions during iTRAQ and bioinformatic analysis. The reactive oxygen species metabolic process was the most common enrichment pathway identified by Gene Ontology analysis, while ORM2, PRDX2, GPX3, HP, HBB, ANXA5, PFN1, CFL1, and S100A11 were key proteins identified by STRING and MCODE analysis. ORM2 showed increased expression in patients with CAS plaques, and ORM2 was accumulated in smooth muscle cells. Oleic acid increased the lipid accumulation and ORM2 and PRDX6 expressions in the VSMCs. The recombinant-ORM2 also increased the lipid accumulation and reactive oxygen species (ROS) in the VSMCs. The expressions of ORM2 and PRDX-6 were correlated, and MJ33 (an inhibitor of PRDX6-PLA2) decreased ROS production and lipid accumulation in VSMCs. CONCLUSION: ORM2 may be a biomarker for CAS; it induced lipid accumulation and ROS production in VSMCs during atherosclerosis plaque formation. However, the relationships between ORM2 and PRDX-6 underlying lipid accumulation-induced plaque vulnerability require further research.

Effectiveness of collateral arteries embolization before endovascular aneurysm repair to prevent type II endoleaks: A systematic review and meta-analysis.

OBJECTIVES: This study aimed to evaluate the effect of preventive collateral arteries embolization before endovascular aneurysm repair (EVAR) to reduce type II endoleaks (T2EL), aneurysm enlargement, and re-interventions. METHODS: A comprehensive search of PubMed, MEDLINE, Web of Science, and Embase was conducted to identify articles in English, related to preventive collateral arteries embolization before EVAR, published until October 2020. RESULTS: A total of 12 relevant studies, including 11 retrospective studies and one randomized controlled trial, were identified and fulfilled the specified inclusion criteria. A total of 1706 patients in 11 studies were involved in the meta-analysis. The overall incidence of T2EL was 17.3% in the embolization group vs. 34.5% in the control group (OR 0.36, p < 0.01). The incidence of persistent T2EL was 15.3% vs. 30.0% (OR 0.37, p < 0.01). Five studies reported the incidence of sac enlargement, with the rate 10.2% vs. 24.9% (OR 0.25, p < 0.01). Nine studies reported T2EL related re-interventions, and it was 1.3% in the embolization group and 10.4% in control (OR 0.14, p < 0.01). The technical success of collateral arteries embolization was 92.1% (455/494) in the 12 studies. 1.2% (10/829) patients suffered a mild complication of collateral arteries embolization, and 2/829 patients died because of the embolization. CONCLUSION: Collateral arteries embolization is a promising measure to prevent the occurrence of T2EL, sac enlargement, and re-intervention. High-quality studies need to be conducted to provide stronger evidence-based medical suggestions about the embolize operation.

The Efficacy of Transcarotid Artery Revascularization With Flow Reversal System Compared to Carotid Endarterectomy: A Systematic Review and Meta-Analysis.

Background: Carotid artery stenosis has long been a critical cause of stroke and death, and it can seriously affect the life quality. Transcarotid artery revascularization (TCAR) and carotid endarterectomy (CEA) are both feasible therapies for this disease. This systematic review and meta-analysis aim to evaluate if the efficacy of the two approaches is comparable. Methods: Clinical studies up to March 2021 were searched through PubMed, Embase, and Scopus from a computer. The screening process was designed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. Newcastle-Ottawa Scale (NOS) was used for methodological quality assessment of works of literature meeting the inclusion criteria, and Review Manager 5.4 was used for data synthesis. The I2 statistic was performed to measure the heterogeneity, and M-H/I-V fixed or random model was utilized depending on the I2 value. The evidence evaluation was accomplished based on grades of recommendation, assessment, development, and evaluation (GRADE) online tool. Results: A total of 14,200 subjects (six comparative studies) were finally included in this pooled study. There is no statistical discrepancy between the two treatments on reducing stroke/death/myocardial infarction (odds ratio [OR] 0.85, 95% CI 0.67-1.07), stroke (OR 1.03, 95% CI 0.77-1.37), or death (OR 1.14, 95% CI 0.67-1.94). Besides, TCAR is associated with a lower incidence of myocardial infarction (P = 0.004), cranial nerve injury (P < 0.00001), and shorter procedure time (P < 0.00001) than CEA among the overall cohort. Conclusions: TCAR is a rapidly developing treatment that reaches a comparable prognosis to CEA and significantly reduces the risk of myocardial infarction under the well-matched condition, which is a dependable choice for patients with carotid stenosis.

Bioabsorbable Drug-Eluting Stent Versus Bare Metal Stent in Iliac Artery Evaluated by Optical Coherence Tomography: An In Vivo Study in Porcine.

OBJECTIVE: This study aimed to compare, using optical coherence tomography (OCT), the outcomes of bioabsorbable drug-eluting stent with those of bare metal stent (BMS) following implantation in porcine iliac artery. METHODS: After the placement of BMS and bioabsorbable drug-eluting stents, we used OCT and digital subtraction angiography to investigate stent appositions, arterial neointima, evagination, and restenosis at 1 and 3 months. RESULTS: At 1 and 3 months after stent implantation, OCT study was performed to investigate 32 stents and 21 788 struts. Thirty-three malapposed struts were found in the bioabsorbable drug-eluting stent groups and 2 were found in BMS groups. The average neointimal thickness, area, and in-stent stenosis were significantly lower in bioabsorbable drug-eluting stents than in BMS, while the frequency of malapposed struts was higher in the bioresorbable drug-eluting stent groups. Average neointimal thickness was lower in bioabsorbable drug-eluting stents than in BMS at 1 (0.19 ± 0.09 vs 0.67 ± 0.75 mm; P < .001) and 3 months (0.21 ± 0.08 vs 1.52 ± 0.28 mm; P < .001). CONCLUSION: Our study suggested that bioabsorbable drug-eluting stent is more effective in decreasing arterial restenosis than BMS in animal models.

Sonography and Transthoracic Echocardiography for Diagnosis of Systemic Cardiovascular Metastatic Tumor Thrombi.

Sonography and transthoracic echocardiography (TTE) are seldom used for assessment of metastatic tumor thrombi in the cardiovascular system in routine clinical practice. We performed this retrospective study to evaluate the combination of sonography with TTE for diagnosis of metastatic tumor thrombi in heart and systemic vessels. Vascular, abdominal, pelvic, and small-part sonography was applied in 18 patients, and TTE was conducted simultaneously in 14 patients. Tumor thrombi invaded into the inferior vena cava system in 12 patients, superior vena cava system in 5 patients, and aorta in 1 patient; they extended to the right cardiac chambers in 11 patients. Six patients had diagnoses by pathologic examination. The primary neoplasms were identified by conventional imaging in 17 patients. The morphologic and echogenic characteristics of the tumor thrombi were diverse and depended on their original tumors. The thrombi were either contiguous or discrete from the original tumors. The neoplastic vascularity of the thrombi and the invasive extension were the primary characteristics that distinguished them from bland thrombi. Simultaneous application of sonography and TTE is a feasible way to comprehensively evaluate cardiovascular metastatic tumor thrombi in most patients.

Network meta-analysis of balloon angioplasty, nondrug metal stent, drug-eluting balloon, and drug-eluting stent for treatment of infrapopliteal artery occlusive disease.

PURPOSE: We aimed to conduct a network meta-analysis of mixed treatments for the infrapopliteal artery occlusive disease. METHODS: We searched randomized controlled trials (RCTs) regarding balloon angioplasty (BA), nondrug metal stent (NDMS), drug-eluting balloon (DEB), or drug-eluting stent (DES) in PubMed, Embase, CENTRAL, Ovid, Sinomed, and other relevant websites. We selected and assessed the trials that met the inclusion criteria and conducted a network meta-analysis using the ADDIS software. RESULTS: We included 11 relevant trials. We analyzed data of 1322 patients with infrapopliteal artery occlusive disease, of which 351 were in the NDMS vs. DES trials, 231 in the NDMS vs. BA trials, 490 in the BA vs. DEB trials, 50 in the DEB vs. DES trials, and 200 in the BA vs. DES trials. The network meta-analysis indicated that with NDMS as the reference, DES had a better result with respect to restenosis (odds ratio [OR], 5.16; 95% credible interval [CI], 1.58-18.41; probability of the best treatment, 84%) and amputation (OR, 2.50; 95% CI, 0.81-7.11; probability of the best treatment, 61%) and DEB had a better result with respect to target lesion revascularization (TLR; OR, 3.74; 95% CI, 0.78-17.05; probability of the best treatment, 57%). Moreover, with BA as the reference, NDMS had a better result with respect to technical success (OR, 0.10; 95% CI, 0.00-1.15; probability of the best treatment, 86%). CONCLUSION: Our meta-analysis revealed that DES is a better treatment with respect to short-term patency and limb salvage rate, NMDS may provide a better technical success, and DEB and DES are good choices for reducing revascularization.

Sirt1 mediates the effect of the heme oxygenase inducer, cobalt protoporphyrin, on ameliorating liver metabolic damage caused by a high-fat diet.

BACKGROUND & AIMS: Heme oxygenase 1 (HO-1)-mediated increases in adiponectin, ameliorate the deleterious effects of obesity and metabolic syndrome; however, the effect of HO-1 on hepatic lipid metabolism remains elusive. The aim of this study is to evaluate the role of HO-1 in hepatic lipid metabolism. METHODS: Functional studies were performed using C57BL/6J (WT) mice and Sirt1 liver specific mutant (Sirt1-deficient) mice. The molecular mechanism was explored in primary hepatocytes and mouse liver. RESULTS: Chronic exposure to high-fat diet (HFD) induced hepatic steatosis in WT mice. Treatment of WT mice on HFD with cobalt protoporphyrin (CoPP), an inducer of HO-1 activity, decreased body weight and visceral fat content, reduced intracellular hepatic triglyceride and serum total cholesterol concentrations, and decreased liver lipid droplet formation. Compared with WT mice, the administration of CoPP to Sirt1-deficient mice on HFD increased visceral fat content, and slightly promoted liver lipid droplet formation. CoPP improved glucose tolerance and insulin sensitivity in WT mice on HFD, but compromised insulin sensitivity in Sirt1-deficient mice on HFD. Furthermore, CoPP-induced Sirt1 expression and decreased sterol regulatory element binding protein 1c (SREBP-1c) expression in WT mice on HFD. However, CoPP promoted SREBP-1c expression in Sirt1-deficient hepatocytes, which was reversed by a protein tyrosine phosphatase 1b inhibitor. Additionally, while the administration of CoPP to WT mice on HFD improved antioxidant and anti-inflammatory states, these CoPP-mediated effects were abolished in Sirt1-deficient mice. CONCLUSIONS: Sirt1 mediates the effect of CoPP on ameliorating liver metabolic damage caused by HFD.

Combined Cathepsin S and hs-CRP predicting inflammation of abdominal aortic aneurysm.

OBJECTIVES: Cathepsin S (Cat S) protein expression is increased in human abdominal aortic aneurysm (AAA) lesions and Cat S has been suggested a direct role by promoting inflammatory response partly in experimental AAA. The purpose of this study is to observe the expression of serum Cat S and hs-CRP and its clinical significance in AAA patients. DESIGN AND METHODS: We collected serum samples from 31 AAA patients and 32 controls. Cat S and hs-CRP levels were measured by a sandwich-type enzyme-linked immunosorbent assay (ELISA) and an enhanced immunoturbidimetric assay respectively. The maximum diameter of the AAA was identified by ultrasonography. RESULTS: The patients with AAA had higher serum Cat S and hs-CRP levels than the controls (p<0.05). Furthermore, human serum Cat S levels were strongly correlated with hs-CRP by the nonparametric Spearman correlation tests (B=0.849, p<0.05). Based on Pearson's correlation test, human serum Cat S and hs-CRP levels were positively correlated with AAA diameter size (p<0.05). Cat S was correlated independently with the hs-CRP in all subjects (p<0.01). After adjustment for the maximum diameter of the abdominal aorta-associated variables, Cat S combined hs-CRP (R(2)=0.801) is better than Cat S (R(2)=0.740) in predicting the maximum diameter of AAA lesions. CONCLUSION: Combined serum Cat S and hs-CRP levels are better in predicting the inflammatory activity of AAA lesions in the clinical setting.

Cysteine protease cathepsins and matrix metalloproteinases in the development of abdominal aortic aneurysms.

Both cysteine protease cathepsins and matrix metalloproteinases are implicated in the pathogenesis of abdominal aortic aneurysms (AAAs) in humans and animals. Blood and aortic tissues from humans or animals with AAAs contain much higher levels of these proteases, and often lower levels of their endogenous inhibitors, than do blood and aortic tissues from healthy subjects. Protease- and protease inhibitor-deficient mice and synthetic protease inhibitors have affirmed that cysteinyl cathepsins and matrix metalloproteinases both participate directly in AAA development in several experimental model systems. Here, we summarize our current understanding of how proteases contribute to the pathogenesis of AAA, and discuss whether proteases or their inhibitors may serve as diagnostic biomarkers or potential therapeutic targets for this common human arterial disease.

Zinc finger protein-activating transcription factor up-regulates vascular endothelial growth factor-a expression in vitro / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To construct the zinc finger protein-activating transcription factor (ZFP-ATF) plasmid and evaluate its efficacy in inducing vascular endothelial growth factor (VEGF) expression in EY.HY926 endothelial cells.</p><p><b>METHODS</b>Firstly, we constructed the ZFP-ATF plasmid, then testified the quantity of VEGF protein in EY.HY926 endothelial cells after transfected with ZFP-ATP plasmid by Western blot, finally, we used the RT-PCR to testify whether the ZFP-ATF can stimulate expression of VEGF splice variants.</p><p><b>RESULTS</b>The ZFP-ATF DNA sequences were located the multiclone sites of PVAX1 vector between the site of BamH1and Xhol.Western blot result showed VEGF expression in EY.HY926 endothelial cells transfected with ZFP-ATF plasmid was significantly higher than that in cells transfected with VEGF165 (19.95±3.95 vs.12.15±1.55 μg÷μL, P<0.01).RT-PCR result showed VEGF-A mRNA expression level induced by ZFP-ATF was high than that induced by VEGF165.</p><p><b>CONCLUSION</b>ZFP-ATF can up-regulate the VEGF-A expression in comparison with VEGF165, which might have beneficial effects in angiogenesis process.</p>

Human cytomegalovirus infection is a novel etiology for essential hypertension.

Essential hypertension is a major risk factor for cardiovascular, cerebrovascular, and renal diseases. However, the underlying cause and pathologic mechanisms of essential hypertension are poorly understood. Vascular inflammation and endothelial dysfunction are implicated in the pathogenesis of hypertension based on associations with elevated expression of adhesion molecules and chemokines and dysfunctional nitric oxide synthase. Human cytomegalovirus (HCMV) has been implicated in several cardiovascular disorders, including atherosclerosis, coronary heart disease, and cardiac transplant arteriopathy. Recent studies have suggested that HCMV is associated with cardiovascular disorders through impaired endothelial nitric oxide synthase function and subsequent endothelial dysfunction, which manifest as impaired vasculature dilation in vivo. However, direct links between human cytomegalovirus infection and essential hypertension remain undefined. Based on current studies, we present a hypothesis that human cytomegalovirus is an opportunistic pathogen that causes essential hypertension by disrupting nitric oxide synthesis and immune defense and by activating inflammation and the renin-angiotensin system.

[Comparison of open and endovascular repair for abdominal aortic aneurysm mid-term outcomes: a single center randomized controlled trial].

OBJECTIVE: To compare the effects of open and endovascular repair for abdominal aortic aneurysm. METHODS: Between January 2009 and January 2011, 84 patients were randomized to endovascular aneurysm repair (EVAR) or open repair. There were 48 patients in EVAR group, 42 cases were male (87.5%), 6 cases were female (12.5%), aged from 50 to 83 years with a mean of 70.8 years. There were 36 patients in open repair group, 31 cases were male (86.1%), 5 cases were female (13.9%), aged from 50 to 80 years with a meal of 67.4 years. The results of perioperative period and follow-up were analyzed. RESULTS: Between the two groups, there was significant difference on operative time (t = 9.863, P = 0.000), blood loss (t = 4.647, P = 0.000), blood transfusion (t = 3.334, P = 0.002), hospital stay (t = 2.327, P = 0.022), and medical expense (t = 2.314, P = 0.023). There was no significant difference for perioperative complications (χ(2) = 0.480, P = 0.488). There was no significant difference for complications (χ(2) = 0.664, P = 0.415) and mortality (P = 0.429) during 3 months follow-up. There was no significant difference for complications during 6 months follow-up (χ(2) = 0.128, P = 0.720). CONCLUSIONS: Operative time, blood loss and transfusion, hospital stay in EVAR group are less than which in open repair group, the medical expense of EVAR was higher than open repair. There is no significant difference for complications during 6 months follow-up between 2 groups. Long-term follow-up and more patents are needed to analyze survival rate and long-term complications.

Reinstate the damaged VEGF signaling pathway with VEGF-activating transcription factor.

OBJECTIVE: To investigate the role of vascular endothelial growth factor-activating transcriptional factor (VEGF-ATF) on the VEGF signaling pathway in diabetes mellitus. METHODS: Totally, 20 C57BL/6 mice fed with high fat diet was induced into diabetes mellitus. Ten diabetes mellitus mice received a lower limb muscle injection with VEGF-ATF plasmid, and another ten were as control. VEGF-ATF is an engineered transcription factor designed to increase VEGF expression. Three days later, mice were sacrificed and the injected gastrocnemius was used for analysis. VEGF mRNA and protein expressions were examined by real-time PCR and ELISA respectively. VEGF receptor 2 mRNA expression was tested with RT-PCR. Phosphorylated Akt, Akt, endothelial nitric oxide synthase (eNOS), and phosphorylated eNOS were assessed by western blot. RESULTS: At 3 days post-injection, in mice with diabetes mellitus, VEGF gene transfer increased VEGF mRNA copies and VEGF protein expression in injected muscles compared with control; and reinstated the impaired VEGF signaling pathway with increasing the ratios of phosphorylated Akt/Akt and phosphorylated eNOS/eNOS. However, it did not affect the expression of VEGF receptor 2 mRNA. CONCLUSION: Gene transfer with VEGF-ATF is able to reinstate the impaired VEGF downstream pathway, and potentially promote therapeutic angiogenesis in mice with diabetes mellitus.

Myoglobin over-expression attenuates angiogenic response in hindlimb ischemia in mice.

BACKGROUND: Myoglobin is expressed exclusively in striated skeletal muscles and has been implicated in nitric oxide scavenging. Accumulating data suggest a critical role for nitric oxide in both the endogenous and therapeutic angiogenic response to ischemia. A clear role for myoglobin in ischemic skeletal muscle is uncertain. We hypothesized that myoglobin overexpression has an adverse impact on the angiogenic response to ischemia. METHODS: Muscle-specific myoglobin over-expressing transgenic mice (MbTG, n = 11), wild type littermates (WT, n = 23) underwent unilateral femoral artery ligation and excision. Laser doppler perfusion imaging was used to monitor changes in hindlimb perfusion before surgery and weekly after surgery up to 28 days. Tissue ischemia was assessed by a necrosis incidence. Upon termination of the experiment (28 days after surgery), skeletal muscles (gastrocnemius, and tibialis anterior) were harvested, the distal part of the muscle was frozen and embedded for histology study, the proximal part was used either to detect vascular endothelial growth factor (VEGF) level with enzyme-linked immunosorbent assays (ELISA) or to determine the proliferation (proliferating cell nuclear antigen (PCNA)) and apoptosis (Bax, and Bcl-2) condition in ischemic muscle by Western blotting. Capillaries were stained with endothelial phosphate alkaline staining and vascular density was expressed in capillaries/fiber. RESULTS: The recovery of perfusion in MbTG mice was similar to that of WT mice on day 7 (0.485 +/- 0.095 vs 0.500 +/- 0.084) but was significantly less on day 14 (0.536 +/- 0.086 vs 0.623 +/- 0.077, P < 0.05), day 21 (0.588 +/- 0.082 vs 0.684 +/- 0.068, P < 0.01) and day 28 (0.606 +/- 0.079 vs 0.733 +/- 0.093, P < 0.01). The necrosis incidence was higher in MbTG than in WT (54.5% vs 21.6%). Vascular density was less in MbTG compared with that in WT (gastrocnemius 0.19 +/- 0.08 vs 0.30 +/- 0.08, P < 0.05; tibialis anterior 0.22 +/- 0.11 vs 0.33 +/- 0.04, P < 0.05). With ischemic injury, the VEGF level was increased in both MbTG and WT (45.2% and 20.4%, respectively). Western blotting showed that after hindlimb ischemia the proliferation was similar in both MbTG and WT, however, apoptosis was increased in MbTG relative to WT, shown as more expression of Bax and less expression of Bcl-2. CONCLUSION: An increase in expression of myoglobin protein in skeletal muscle reduces the endogenous perfusion recovery following surgically induced hind-limb ischemia.