scholarly journals Creating a Natural Vascular Scaffold by Photochemical Treatment of the Extracellular Matrix for Vascular Applications

2022 ◽  
Vol 23 (2) ◽  
pp. 683
Author(s):  
Katalin Kauser ◽  
Kevin S. Warner ◽  
Blake Anderson ◽  
Edgar Dalles Keyes ◽  
RB Hayes ◽  
...  

The development of bioscaffolds for cardiovascular medical applications, such as peripheral artery disease (PAD), remains to be a challenge for tissue engineering. PAD is an increasingly common and serious cardiovascular illness characterized by progressive atherosclerotic stenosis, resulting in decreased blood perfusion to the lower extremities. Percutaneous transluminal angioplasty and stent placement are routinely performed on these patients with suboptimal outcomes. Natural Vascular Scaffolding (NVS) is a novel treatment in the development for PAD, which offers an alternative to stenting by building on the natural structural constituents in the extracellular matrix (ECM) of the blood vessel wall. During NVS treatment, blood vessels are exposed to a photoactivatable small molecule (10-8-10 Dimer) delivered locally to the vessel wall via an angioplasty balloon. When activated with 450 nm wavelength light, this therapy induces the formation of covalent protein–protein crosslinks of the ECM proteins by a photochemical mechanism, creating a natural scaffold. This therapy has the potential to reduce the need for stent placement by maintaining a larger diameter post-angioplasty and minimizing elastic recoil. Experiments were conducted to elucidate the mechanism of action of NVS, including the molecular mechanism of light activation and the impact of NVS on the ECM.

Blood ◽  
2002 ◽  
Vol 100 (4) ◽  
pp. 1220-1223 ◽  
Author(s):  
Clare Muckian ◽  
Anthony Fitzgerald ◽  
Anne O'Neill ◽  
Anna O'Byrne ◽  
Desmond J. Fitzgerald ◽  
...  

Although common genetic variants in platelet collagen receptors influence platelet activation and thrombosis, the impact of polymorphisms in collagen genes on cardiovascular disease is unknown. To evaluate this, we genotyped a highly polymorphic intronic tandem repeat of the COL3A1 gene, encoding collagen type III, alpha 1. This revealed 4 common alleles (COL3A1-1, -2, -3, and -4). The 2 populations studied were as follows: (1) a cross-sectional study of 703 acute coronary syndrome (ACS) patients with myocardial infarction (MI) and unstable angina, and (2) a prospective study of 924 Caucasian patients from the OPUS (Orbofiban in Patients with Unstable coronary Syndromes)-TIMI-16 trial of the oral GPIIb/IIIa antagonist orbofiban. In addition, we studied 306 control subjects and 224 patients with stable angina. In the case-control population, COL3A1-4 carriers were protected against ACS (odds ratio [OR] = 0.57, 95% CI = 0.35-0.91, P = .02) and stable angina (OR = 0.35, 95% CI = 0.16-0.74, P = .006). In the OPUS population, allele 4 again appeared protective against composite end points (death, MI, stroke, recurrent ischemia, and urgent rehospitalization) (relative risk [RR] = 0.41, 95% CI = 0.17-1.00). There were significant interactions between COL3A1-1 and -3 variants and treatment. Allele COL3A1-3 was associated with an increased risk of the composite end point (RR = 1.65, 95% CI = 1.07-2.55) in patients randomized to orbofiban, but appeared protective in placebo patients (RR = 0.53, 95% CI = 0.28-0.98). We conclude that variants in the COL3A1 gene, the product of which is a vessel-wall protein and platelet ligand, modulate the risk of coronary artery disease and could also modulate the response to antithrombotic therapy. This is the first reported association between polymorphisms of extracellular matrix components and cardiovascular risk.


1996 ◽  
Vol 84 (5) ◽  
pp. 883-887 ◽  
Author(s):  
Gayle S. Storey ◽  
Michael P. Marks ◽  
Michael Dake ◽  
Alexander M. Norbash ◽  
Gary K. Steinberg

✓ The authors report initial results and follow up using stent placement to treat atherosclerotic stenosis in vertebral arteries. Three patients with severe atherosclerotic vascular disease underwent vertebral artery stent placement using a balloon expandable stent. Medical therapy (aspirin and warfarin) and conventional percutaneous angioplasty failed to resolve the disease and the patients developed symptomatic restenosis within 3 months of angioplasty. Two patients had symptoms of anterior circulation ischemia with carotid artery occlusions and reduced supply to the anterior circulation from the stenosed vertebral arteries. One patient had recurrent posterior circulation symptoms. Stents were successfully placed in all three, resulting in immediate reversal of stenosis and resolution of symptoms. Clinical follow-up study (mean 9 months) has shown no recurrent symptoms in the patient with posterior circulation symptoms, but the two patients with anterior circulation ischemia did develop recurrent symptoms. Angiographic follow up in these two patients at 3 months and 1 year, however, demonstrated continued patency of vertebral artery lumina. They underwent extracranial—intracranial bypass surgery to relieve their symptoms. This experience suggests stents can be placed without complication in the proximal vertebral arteries and may have an adjunctive role in the treatment of atherosclerotic cerebrovascular disease following unsuccessful angioplasty.


2013 ◽  
Vol 11 (5) ◽  
pp. 779-784 ◽  
Author(s):  
Vasilios G. Athyros ◽  
Konstantinos Tziomalos ◽  
Niki Katsiki ◽  
Thomas D. Gossios ◽  
Olga Giouleme ◽  
...  

2021 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
F Andre ◽  
S Seitz ◽  
P Fortner ◽  
R Sokiranski ◽  
F Gueckel ◽  
...  

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Siemens Healthineers Introduction Coronary CT angiography (CCTA) plays an increasing role in the detection and risk stratification of patients with coronary artery disease (CAD). The Coronary Artery Disease – Reporting and Data System (CAD-RADS) allows for standardized classification of CCTA results and, thus, may improve patient management. Purpose Aim of this study was to assess the impact of CCTA in combination with CAD-RADS on patient management and to identify the impact of cardiovascular risk factors (CVRF) on CAD severity. Methods CCTA was performed on a third-generation dual-source CT scanner in patients, who were referred to a radiology centre by their attending physicians. In a total of 4801 patients, CVRF were derived from medical reports and anamnesis. Results The study population consisted of 4770 patients (62.0 (54.0-69.0) years, 2841 males) with CAD (CAD-RADS 1-5), while 31 patients showed no CAD and were excluded from further analyses. Age, male gender and the number of CVRF were associated with more severe CAD stages (all p < 0.001). 3040 patients (63.7 %) showed minimal or mild CAD requiring optimization of CVRF i.e. medical therapy but no further assessment at his time. A group of 266 patients (5.6 %) had a severe CAD defined as CAD-RADS 4B/5. In the multivariate regression analysis, age, male gender, history of smoking, diabetes mellitus and hyperlipidaemia were significant predictors for severe CAD, whereas arterial hypertension and family history of CAD did not reach significance. Of note, a subgroup of 28 patients (10.5 %) with a severe CAD (68.5 (65.5-70.0) years, 26 males, both p = n.s.) had no CVRF. Conclusions CCTA in combination with the CAD-RADS allowed for effective risk stratification of CAD patients. The majority of the patients showed non-obstructive CAD and, thus, could be treated conservatively without the need for further CAD assessment. CVRF out of arterial hypertension and family history had an impact on CAD severity reflected in higher CAD-RADs gradings. Of note, a relevant fraction of patients with CAD did not have any CVRF and, thus, may not be covered by risk stratification models. CAD-RADS n Age (years) Males (%) 1 1453 56.0 (50.0-62.0) 623 (42.9 %) 2 1587 62.0 (55.0-69.0) 918 (57.8 %) 3 1067 66.0 (59.0-71.0) 749 (70.2 %) 4A 397 66.0 (59.0-72.0) 317 (79.8 %) 4B 162 67.0 (61.0-74.0) 139 (85.8 %) 5 104 66.0 (58.5.0-77.0) 95 (91.3 %)


Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1046
Author(s):  
Jorge Martinez ◽  
Patricio C. Smith

Desmoplastic tumors correspond to a unique tissue structure characterized by the abnormal deposition of extracellular matrix. Breast tumors are a typical example of this type of lesion, a property that allows its palpation and early detection. Fibrillar type I collagen is a major component of tumor desmoplasia and its accumulation is causally linked to tumor cell survival and metastasis. For many years, the desmoplastic phenomenon was considered to be a reaction and response of the host tissue against tumor cells and, accordingly, designated as “desmoplastic reaction”. This notion has been challenged in the last decades when desmoplastic tissue was detected in breast tissue in the absence of tumor. This finding suggests that desmoplasia is a preexisting condition that stimulates the development of a malignant phenotype. With this perspective, in the present review, we analyze the role of extracellular matrix remodeling in the development of the desmoplastic response. Importantly, during the discussion, we also analyze the impact of obesity and cell metabolism as critical drivers of tissue remodeling during the development of desmoplasia. New knowledge derived from the dynamic remodeling of the extracellular matrix may lead to novel targets of interest for early diagnosis or therapy in the context of breast tumors.


Author(s):  
Rutao Wang ◽  
Scot Garg ◽  
Chao Gao ◽  
Hideyuki Kawashima ◽  
Masafumi Ono ◽  
...  

Abstract Aims To investigate the impact of established cardiovascular disease (CVD) on 10-year all-cause death following coronary revascularization in patients with complex coronary artery disease (CAD). Methods The SYNTAXES study assessed vital status out to 10 years of patients with complex CAD enrolled in the SYNTAX trial. The relative efficacy of PCI versus CABG in terms of 10-year all-cause death was assessed according to co-existing CVD. Results Established CVD status was recorded in 1771 (98.3%) patients, of whom 827 (46.7%) had established CVD. Compared to those without CVD, patients with CVD had a significantly higher risk of 10-year all-cause death (31.4% vs. 21.7%; adjusted HR: 1.40; 95% CI 1.08–1.80, p = 0.010). In patients with CVD, PCI had a non-significant numerically higher risk of 10-year all-cause death compared with CABG (35.9% vs. 27.2%; adjusted HR: 1.14; 95% CI 0.83–1.58, p = 0.412). The relative treatment effects of PCI versus CABG on 10-year all-cause death in patients with complex CAD were similar irrespective of the presence of CVD (p-interaction = 0.986). Only those patients with CVD in ≥ 2 territories had a higher risk of 10-year all-cause death (adjusted HR: 2.99, 95% CI 2.11–4.23, p < 0.001) compared to those without CVD. Conclusions The presence of CVD involving more than one territory was associated with a significantly increased risk of 10-year all-cause death, which was non-significantly higher in complex CAD patients treated with PCI compared with CABG. Acceptable long-term outcomes were observed, suggesting that patients with established CVD should not be precluded from undergoing invasive angiography or revascularization. Trial registration SYNTAX: ClinicalTrials.gov reference: NCT00114972. SYNTAX Extended Survival: ClinicalTrials.gov reference: NCT03417050. Graphic abstract


2020 ◽  
Vol 6 (3) ◽  
pp. 410-413
Author(s):  
Petra J. Kluger ◽  
Svenja Nellinger ◽  
Simon Heine ◽  
Ann-Cathrin Volz

AbstractThe extracellular matrix (ECM) naturally surrounds cells in humans, and therefore represents the ideal biomaterial for tissue engineering. ECM from different tissues exhibit different composition and physical characteristics. Thus, ECM provides not only physical support but also contains crucial biochemical signals that influence cell adhesion, morphology, proliferation and differentiation. Next to native ECM from mature tissue, ECM can also be obtained from the in vitro culture of cells. In this study, we aimed to highlight the supporting effect of cell-derived- ECM (cdECM) on adipogenic differentiation. ASCs were seeded on top of cdECM from ASCs (scdECM) or pre-adipocytes (acdECM). The impact of ECM on cellular activity was determined by LDH assay, WST I assay and BrdU assay. A supporting effect of cdECM substrates on adipogenic differentiation was determined by oil red O staining and subsequent quantification. Results revealed no effect of cdECM substrates on cellular activity. Regarding adipogenic differentiation a supporting effect of cdECM substrates was obtained compared to control. With these results, we confirm cdECM as a promising biomaterial for adipose tissue engineering.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Hiroyuki Yamamoto ◽  
Akihide Konishi ◽  
Toshiro Shinke ◽  
Hiromasa Otake ◽  
Masaru Kuroda ◽  
...  

Abstract Background The impact of reduction in glycemic excursion on coronary plaques remains unknown. This study aimed to elucidate whether a dipeptidyl peptidase 4 inhibitor could reduce the glycemic excursion and stabilize the coronary plaques compared with conventional management in coronary artery disease (CAD) patients with impaired glucose tolerance (IGT). Methods This was a multicenter, randomized controlled trial including CAD patients with IGT under lipid-lowering therapy receiving either vildagliptin (50 mg once a day) or no medication (control group) regarding glycemic treatment. The primary endpoint was changes in the minimum fibrous cap thickness and lipid arc in non-significant native coronary plaques detected by optical coherence tomography at 6 months after intervention. Glycemic variability expressed as the mean amplitude of glycemic excursion (MAGE) measured with a continuous glucose monitoring system was evaluated before and 6 months after intervention. Results A total of 20 participants with 47 lesions were allocated to either the vildagliptin group (10 participants, 22 lesions) or the control group (10 participants, 25 lesions). The adjusted difference of mean changes between the groups was − 18.8 mg/dl (95% confidence interval, − 30.8 to − 6.8) (p = 0.0064) for the MAGE (vildagliptin, − 20.1 ± 18.0 mg/dl vs. control, 2.6 ± 12.7 mg/dl), − 22.8° (− 40.6° to − 5.1°) (p = 0.0012) for the mean lipid arc (vildagliptin, − 9.0° ± 25.5° vs. control, 15.8° ± 16.8°), and 42.7 μm (15.3 to 70.1 μm) (p = 0.0022) for the minimum fibrous cap thickness (vildagliptin, 35.7 ± 50.8 μm vs. control, − 15.1 ± 25.2 μm). Conclusions Vildagliptin could reduce the MAGE at 6 months and may be associated with the decreased lipid arc and increased minimum FCT of the coronary plaques in CAD patients with IGT as compared with the control group. These findings may represent its potential stabilization effect on coronary plaques, which are characteristic in this patient subset. Trial registration Registered in the UMIN clinical trial registry (UMIN000008620), Name of the registry: VOGUE trial, Date of registration: Aug 6, 2012, URL: https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000010058


2021 ◽  
Vol 49 (4) ◽  
pp. 030006052110065
Author(s):  
Hao Ren ◽  
Jie Liu ◽  
Jiwei Zhang ◽  
Baixi Zhuang ◽  
Weiguo Fu ◽  
...  

Objective To assess the association between post-balloon angioplasty dissection and the mid-term results of the AcoArt I trial evaluating complex femoropopliteal artery disease. Methods The outcome data for 144 patients from the AcoArt 1 trial were reanalysed. These patients were randomly divided into percutaneous transluminal angioplasty (PTA) and drug-coated balloons (DCB) groups. The primary endpoint was the primary patency (PP) rate and clinically-driven target lesion revascularisation at 24 months. Results After 24 months of follow-up, the PP rate of dissection cases in the PTA group was lower vs non-dissection cases. In patients receiving a bailout stent for dissection, the PP rate in the PTA group was lower vs the DCB group. Cox regression analysis showed that dissection decreased the PP rate; mild dissection reduced the PP rate as follows: 52%, PTA group and 19%, DCB group. With severe dissection, the PP rate reduction was as follows: 75%, PTA group and 73%, DCB group. Conclusions The mid-term follow-up showed that post-balloon angioplasty dissection reduced the PP rate in the PTA group but not in the DCB group. Additionally, in patients receiving a bailout stent for dissection, the DCB group had a better PP rate than the PTA group.


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