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The Canadian Journal of Cardiology Feb 2006Cilostazol is a phosphodiesterase III inhibitor with pharmacological effects that include vasodilation, inhibition of platelet activation and aggregation, inhibition of... (Review)
Review
Cilostazol is a phosphodiesterase III inhibitor with pharmacological effects that include vasodilation, inhibition of platelet activation and aggregation, inhibition of thrombosis, increased blood flow to the limbs, improvement in serum lipids with lowering of triglycerides and elevation of high density lipoprotein cholesterol, and inhibition of vascular smooth muscle cell growth. Cilostazol has been shown in multiple randomized clinical trials to result in decreased claudication and improved ability to walk in patients with peripheral arterial disease. In addition, cilostazol has been shown in multiple randomized clinical trials to decrease restenosis in the setting of coronary stent implantation. The purpose of the present paper was to review the vascular effects of cilostazol and to present results of the major clinical trials of the use of cilostazol in peripheral arterial disease and percutaneous coronary intervention with stent implantation.
Topics: Animals; Cell Proliferation; Cilostazol; Coronary Restenosis; Endothelium, Vascular; Humans; Lipids; Peripheral Vascular Diseases; Phosphodiesterase Inhibitors; Platelet Aggregation Inhibitors; Tetrazoles; Tunica Intima
PubMed: 16498513
DOI: 10.1016/s0828-282x(06)70987-4 -
The Journal of Thoracic and... Oct 2015
Topics: Coronary Artery Bypass; Hemodynamics; Humans; Saphenous Vein; Stents; Tunica Intima
PubMed: 26242836
DOI: 10.1016/j.jtcvs.2015.04.064 -
Scientific Reports Mar 2017"Cable-tie" type biodegradable stents with drug-eluting nanofiber were developed to treat rabbit denuded arteries in this study. Biodegradable stents were fabricated...
"Cable-tie" type biodegradable stents with drug-eluting nanofiber were developed to treat rabbit denuded arteries in this study. Biodegradable stents were fabricated using poly-L-lactide film following being cut and rolled into a cable-tie type stent. Additionally, drug-eluting biodegradable nanofiber tubes were electrospun from a solution containing poly (lactic-co-glycolic acid), rapamycin, and hexafluoroisopropanol, and then mounted onto the stents. The fabricated rapamycin-eluting cable-tie stents exhibited excellent mechanical properties on evaluation of compression test and collapse pressure, and less than 8% weight loss following being immersed in phosphate-buffered saline for 16 weeks. Furthermore, the biodegradable stents delivered high rapamycin concentrations for over 4 weeks and achieved substantial reductions in intimal hyperplasia associated with elevated heme oxygenase-1 and calponin level on the denuded rabbit arteries during 6 months of follow-up. The drug-eluting cable-tie type stents developed in this study might have high potential impacts for the local drug delivery to treat various vascular diseases.
Topics: Absorbable Implants; Animals; Calcium-Binding Proteins; Disease Models, Animal; Drug-Eluting Stents; Equipment Design; Heme Oxygenase-1; Male; Microfilament Proteins; Nanofibers; Polyesters; Rabbits; Sirolimus; Tunica Intima; Up-Regulation; Calponins
PubMed: 28273914
DOI: 10.1038/s41598-017-00131-w -
Cardiovascular Diabetology May 2022Individuals with type 2 diabetes mellitus (T2DM) have an increased risk for developing macrovascular disease (MVD) manifested by atherosclerosis. Phenotypically and...
BACKGROUND
Individuals with type 2 diabetes mellitus (T2DM) have an increased risk for developing macrovascular disease (MVD) manifested by atherosclerosis. Phenotypically and functionally different monocyte subsets (classical; CD14CD16, non-classical; CD14CD16, and intermediate; CD14CD16) including pro-angiogenic monocytes expressing Tie2 (TEMs) can be identified. Here we investigated monocyte heterogeneity and its association with T2DM and MVD.
METHODS
Individuals with (N = 51) and without (N = 56) T2DM were recruited and allocated to "non-MVD" or "with MVD" (i.e., peripheral or coronary artery disease) subgroups. Blood monocyte subsets were quantified based on CD14, CD16 and Tie2 expression levels. Plasma levels of Tie2-ligands angiopoietin-1 and angiopoietin-2 were determined using ELISA. Carotid endarterectomy samples from individuals with (N = 24) and without (N = 22) T2DM were stained for intraplaque CD68 macrophages (inflammation) and CD34 (angiogenesis), as plaque vulnerability markers.
RESULTS
Monocyte counts were similar between individuals with T2DM and healthy controls (non-diabetic, non-MVD). Non-classical monocytes were reduced (p < 0.05) in T2DM, whereas the percentage of TEMs within the intermediate subset was increased (p < 0.05). T2DM was associated with increased angiopoietin-1 (p < 0.05) and angiopoietin-2 (p = 0.0001) levels. Angiopoietin-2 levels were higher in T2DM individuals with MVD compared with non-MVD (p < 0.01). Endarterectomized plaques showed no differences in macrophage influx and microvessel number between individuals with and without T2DM.
CONCLUSIONS
Monocyte subset distribution is altered in T2DM with reduced non-classical monocytes and increased TEM percentage in the intermediate monocyte subset. Increased angiopoietin-2 levels together with increased frequency of TEMs might promote plaque vulnerability in T2DM which could however not be confirmed at tissue level in advanced atherosclerotic lesions.
Topics: Angiopoietin-1; Angiopoietin-2; Atherosclerosis; Diabetes Mellitus, Type 2; Humans; Monocytes; Plaque, Atherosclerotic; Receptor, TIE-2; Tunica Intima
PubMed: 35549955
DOI: 10.1186/s12933-022-01497-6 -
Drug Discovery Today Oct 2016The consensus hypothesis on coronary atherosclerosis suggests high LDL-C levels as the major cause and pursues it as the therapeutic target, explicitly assuming: (i)... (Review)
Review
Excessive intimal hyperplasia in human coronary arteries before intimal lipid depositions is the initiation of coronary atherosclerosis and constitutes a therapeutic target.
The consensus hypothesis on coronary atherosclerosis suggests high LDL-C levels as the major cause and pursues it as the therapeutic target, explicitly assuming: (i) tunica intima of human coronaries consists of only one cell layer - endothelium, situated on a thin layer of scarcely cellular matrix; and (ii) subendothelial lipoprotein retention initiates the disease. Facts showed: (i) normal tunica intima invariably consists of multiple cellular layers; and (ii) initial lipid depositions occurred in the deepest layers of tunica intima. This review suggests that coronary atherosclerosis starts with pathological intimal expansion, resulting in intimal hypoxia and neovascularization from adventitial vasa vasorum, facilitating lipoprotein extraction by previously avascular deep intimal tissues. Until the hypothesis incorporates real knowledge, our efforts will probably be off-target.
Topics: Coronary Artery Disease; Coronary Vessels; Humans; Hyperplasia; Lipid Metabolism; Tunica Intima
PubMed: 27265770
DOI: 10.1016/j.drudis.2016.05.017 -
Trends in Cardiovascular Medicine Aug 2006Versican is an abundant proteoglycan in the blood vessel wall that is increased after vascular injury and accumulates in advanced atherosclerotic plaques. Versican is a... (Review)
Review
Versican is an abundant proteoglycan in the blood vessel wall that is increased after vascular injury and accumulates in advanced atherosclerotic plaques. Versican is a large molecule with domains that mediate binding to cytokines, enzymes, lipoproteins, other extracellular matrix molecules, and signaling receptors. There is evidence that versican exists in the normal, as well as the diseased, vessel wall as discrete fragments, which represent these functional domains. We review the literature on versican degradation in vascular tissue and the function of versican domains, all of which suggest that proteolytic modification of versican may have physiologic as well as pathologic implications for the vascular system.
Topics: Animals; Humans; Hyperplasia; Tunica Intima; Vascular Diseases; Versicans
PubMed: 16839865
DOI: 10.1016/j.tcm.2006.03.011 -
Social Science & Medicine (1982) Mar 2009Racial and socioeconomic status (SES) disparities in cardiovascular disease (CVD) risk are well established among adults. However, little is known about disparities in... (Comparative Study)
Comparative Study
Racial and socioeconomic status (SES) disparities in cardiovascular disease (CVD) risk are well established among adults. However, little is known about disparities in CVD risk among adolescents, particularly considering indices of subclinical CVD. Our aim was to examine socioeconomic and racial disparities in subclinical CVD indices among adolescents. We hypothesized that African American and lower SES adolescents would show greater arterial stiffness and intima media thickness compared to Caucasian and higher SES adolescents, respectively. Participants were 81 African American and 78 Caucasian adolescents (mean age=17.8) from two schools in Pittsburgh, PA, USA. Measures of subclinical CVD were pulse wave velocity and intima media thickness, as assessed by Doppler and B-mode ultrasound, respectively. SES indices included parental education, family income, family assets, subjective social status, and census-derived neighborhood SES. Hypotheses were evaluated in multiple linear regression models with the covariates age, gender, body mass index, and systolic blood pressure. Results indicated that African American adolescents were more often in low SES positions than Caucasians. When considered individually, racial and SES disparities in pulse wave velocity, and to a lesser extent, intima media thickness, were evident. When race and SES were considered together, high school education, low or medium income, and low neighborhood SES were associated with higher pulse wave velocity. Fewer assets were associated with higher intima media thickness. In conclusion, racial and SES disparities in indices of subclinical CVD were observed, with findings most pronounced for SES disparities in pulse wave velocity. This study extends previous findings in adults to adolescents, indicating that disparities in arterial stiffness and intima media thickness occur as early as adolescence. Efforts to reduce socioeconomic and racial disparities in CVD should target disparities early in life.
Topics: Adolescent; Black or African American; Blood Flow Velocity; Cardiovascular Diseases; Carotid Arteries; Female; Femoral Artery; Follow-Up Studies; Health Status Disparities; Humans; Linear Models; Male; Pennsylvania; Social Class; Socioeconomic Factors; Tunica Intima; Ultrasonography; White People
PubMed: 19147264
DOI: 10.1016/j.socscimed.2008.12.029 -
Thorax 1994
Review
Topics: Humans; Hypertension, Pulmonary; Infant; Muscle, Smooth, Vascular; Pulmonary Artery; Tunica Intima
PubMed: 7974326
DOI: 10.1136/thx.49.suppl.s39 -
Advances in Chronic Kidney Disease Sep 2009Hemodialysis vascular access dysfunction is a major cause of morbidity and mortality in hemodialysis patients. The most common cause of this vascular access dysfunction... (Review)
Review
Hemodialysis vascular access dysfunction is a major cause of morbidity and mortality in hemodialysis patients. The most common cause of this vascular access dysfunction is venous stenosis as a result of venous neointimal hyperplasia within the perianastomotic region (arteriovenous fistula) or at the graft-vein anastomosis (polytetrafluoroethylene, or PTFE, grafts). There have been few effective treatments to date for venous neointimal hyperplasia, in part, because of the poor understanding of the pathogenesis of venous neointimal hyperplasia. Therefore, this article will (1) describe the pathology of hemodialysis access stenosis in arteriovenous fistulas and grafts, (2) review and describe both current and novel concepts in the pathogenesis of neointimal hyperplasia formation, (3) discuss current and future novel therapies for treating venous neointimal hyperplasia, and (4) suggest future research areas in the field of hemodialysis vascular access dysfunction.
Topics: Arteriovenous Shunt, Surgical; Constriction, Pathologic; Humans; Hyperplasia; Oxidative Stress; Renal Dialysis; Tunica Intima; Veins
PubMed: 19695501
DOI: 10.1053/j.ackd.2009.06.009 -
Journal of Vascular Surgery Jun 2007Although major advances have been made in the prevention and treatment of restenosis following coronary and peripheral interventions, the persistent complications of... (Review)
Review
Although major advances have been made in the prevention and treatment of restenosis following coronary and peripheral interventions, the persistent complications of thrombosis and reintervention remain a mainstay for repeat hospitalizations in this patient population. For many years, a ubiquitous cell surface receptor called alpha(v)beta(3) integrin was the target of investigators in the prevention of restenosis because its interaction with the extracellular matrix was believed to coordinate the migration of smooth muscle cells (SMCs) from the media to the intima, the seminal event in the formation of intimal occlusive lesion. After the publication of uniformly positive animal studies demonstrating that alpha(v)beta(3) integrin blockade led to a significant reduction in new intimal (neointimal) lesion formation, early clinical trials supported the association of avoidance of target lesion revascularization and the use of antagonists to the SMC integrin alpha(v)beta(3) and its related platelet integrin alpha(IIb)beta(3). However, a series of clinical trials subsequently demonstrated that these antagonists did not necessarily prevent revascularizations by inhibiting intimal hyperplasia per se. Additional animal studies subsequently showed that, indeed, in the setting of pre-existing SMCs in the intimal lesion (ie, atherosclerotic plaque, fatty streaks), inhibiting SMC migration by way of beta(3) integrin blockade was an ineffective approach in the prevention of intimal hyperplasia and restenosis. However, given the wealth of basic and clinical information on the alpha(v)beta(3) integrin and its antagonists, we discuss in this article our new approach to this old solution by targeting a new clinical problem of early failure arteriovenous access for hemodialysis. Given the uniqueness of arteriovenous access in that there are essentially no significant atherosclerotic lesions in the artery and vein prior to the anastomosis, the seminal event of the migration of SMCs from the media to the neointima could by targeted once again with beta(3) integrin antagonists.
Topics: Animals; Blood Vessels; Cardiovascular Agents; Cell Proliferation; Constriction, Pathologic; Disease Models, Animal; Humans; Hyperplasia; Integrin alphaVbeta3; Protein Conformation; Tunica Intima; Vascular Patency; Vascular Surgical Procedures
PubMed: 17544022
DOI: 10.1016/j.jvs.2007.02.069