RESUMEN

Percutaneous transluminal coronary angioplasty has revolutionized the management of patients with coronary artery disease. Unfortunately, the procedure's utility is limited by a frequent complication: restenosis. Coronary stenting prevents the elastic recoil and negative remodeling that can occur after angioplasty but, by inciting varying degrees of intimal expansion, it can also produce arterial renarrowing, known as in-stent restenosis (ISR). The precise mechanisms involved in the pathogenesis of ISR are incompletely understood. The recent introduction of drug-eluting stents (DESs) may help prevent ISR. However, DESs have not been universally successful, and they may introduce new complications that require further refinement. This review summarizes the current understanding of the pathogenesis of ISR and provides an objective overview of DESs.

Asunto(s)

Angioplastia Coronaria con Balón/tendencias , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Reestenosis Coronaria/tratamiento farmacológico , Sistemas de Liberación de Medicamentos/métodos , Stents/tendencias , Angioplastia Coronaria con Balón/efectos adversos , Animales , Enfermedad de la Arteria Coronaria/cirugía , Reestenosis Coronaria/prevención & control , Humanos , Stents/efectos adversos

RESUMEN

Amiloride inhibits activation of the Na(+)-H+ exchanger (NHE), a critical step in smooth muscle cell (SMC) growth. While amiloride treatment reduces SMC proliferation and migration, as well as experimental lesion formation, these effects are not exclusively due to NHE inhibition and remain incompletely understood. The purpose of this study was to examine the mechanisms involved in amiloride-induced attenuation of SMC proliferation and migration, looking specifically at the potential role of apoptosis and urokinase plasminogen activator (uPA) activity in these processes. Rabbit SMCs in tissue culture were exposed to 10-80 microM of the amiloride analogue ethyl isopropyl amiloride (EIPA). Compared with controls, EIPA reduced DNA synthesis, cell number, and mitochondrial respiration, but without toxic effects on quiescent or proliferating cells. In a Boyden chamber assay, EIPA reduced uPA-induced SMC migration. Moreover, in a SMC scratch assay EIPA treatment resulted in a 66% reduction in the number of repopulating cells, a 92% decrease in the number of proliferating cells, and a 37-fold increase in the number of apoptotic cells. SMC apoptosis was frequently localized to the scratch edges, where cell proliferation and bcl-2 expression were absent. Finally, uPA enzymatic activity in the cell culture media was lower for EIPA-treated versus control SMCs. Therefore, EIPA inhibits both SMC proliferation and migration by inducing apoptosis and antagonizing uPA activity, respectively, and requires further study as an agent for reducing vascular lesion formation.

Asunto(s)

Amilorida/análogos & derivados , Amilorida/farmacología , Apoptosis/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Inhibidores de Crecimiento/farmacología , Músculo Liso Vascular/citología , Miocitos del Músculo Liso/efectos de los fármacos , Activador de Plasminógeno de Tipo Uroquinasa/antagonistas & inhibidores , Animales , Aorta Abdominal/citología , Aorta Abdominal/efectos de los fármacos , Aorta Abdominal/enzimología , Apoptosis/fisiología , Movimiento Celular/fisiología , Relación Dosis-Respuesta a Droga , Músculo Liso Vascular/efectos de los fármacos , Músculo Liso Vascular/enzimología , Miocitos del Músculo Liso/citología , Miocitos del Músculo Liso/enzimología , Conejos , Activador de Plasminógeno de Tipo Uroquinasa/metabolismo

Asunto(s)

Infarto del Miocardio/terapia , Reperfusión Miocárdica , Terapia Trombolítica , Tomografía Computarizada de Emisión , Anciano , Circulación Coronaria , Femenino , Corazón/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/diagnóstico por imagen , Infarto del Miocardio/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto , Radioisótopos de Rubidio , Resultado del Tratamiento

RESUMEN

In-stent restenosis (ISR) is a growing problem that is without a practical, efficacious treatment strategy. The purpose of this study was to determine the acute outcome of 17 patients with coronary ISR who were treated with the new 8 French (Fr), guide-catheter compatible Flexicut directional atherectomy catheter (Guidant Corporation, Santa Clara, California). Failure to deliver the device occurred in 2/17 ISR lesions. The remaining 15 ISR lesions were successfully debulked (e.g., minimum lumen diameter pre-procedure: 0.30 +/- 0.16 mm; post-atherectomy plus adjuvant therapy: 2.16 +/- 0.57 mm). Of note, the reference vessel diameter was only 2.62 +/- 0.63 mm. In 11/15 tissue specimens, macroscopic or microscopic particles consistent with stent material were found. There was an absence of acute closure or elevations of creatinine phosphokinase levels. Apart from 1 patient who developed recurrent restenosis, all other patients demonstrated either clinical improvement or lack of restenosis during early clinical follow-up (mean, 5 months). We conclude that use of the Flexicut catheter provides satisfactory debulking and early clinical outcomes in patients with ISR. Long-term follow-up of these and additional patients will be helpful in determining the efficacy of the Flexicut atherectomy catheter for the treatment of ISR.

Asunto(s)

Aterectomía Coronaria/instrumentación , Estenosis Coronaria/terapia , Stents , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia , Resultado del Tratamiento

RESUMEN

This study investigated if specific histological features correlate with remodeling in human coronary arteries treated by balloon angioplasty (PTCA). Segments of perfusion-fixed coronary arteries that had undergone antemortem PTCA were obtained from 15 patients and primary atherosclerotic (CAD) lesions obtained from these hearts were used as control lesions. Arterial segments were serially divided to yield 108 sub-segments for PTCA lesions and 38 sub-segments for CAD lesions. A linear regression analysis was used to determine the relationship between 14 histological parameters and an arbitrary index of compensatory arterial enlargement, the external elastic lamina (EEL) index (EELI), defined as the ratio of the area encompassed by the EEL to the sum of the intimal area (IA) + medial area (MA). In PTCA arteries the abundance of plaque microvessels negatively correlated with the EELI (p=0.04), but in CAD arteries there was no relationship between histology and the EELI. The abundance of plaque microvessels correlates with the magnitude of constriction in coronary artery lesions subjected to PTCA. This study provides descriptive insights into the biology of remodeling in human coronary arteries after angioplasty, and suggests that the endothelium may play an important role.

Asunto(s)

Enfermedad de la Arteria Coronaria/patología , Anciano , Anciano de 80 o más Años , Angioplastia Coronaria con Balón , Diferenciación Celular , División Celular , Enfermedad de la Arteria Coronaria/fisiopatología , Enfermedad de la Arteria Coronaria/terapia , Vasos Coronarios/patología , Vasos Coronarios/fisiopatología , Femenino , Humanos , Masculino , Microcirculación , Persona de Mediana Edad

RESUMEN

OBJECTIVES: We sought to directly compare primary stenting with accelerated tissue plasminogen activator (t-PA) in patients presenting with acute ST-elevation myocardial infarction (AMI). BACKGROUND: Thrombolysis remains the standard therapy for AMI. However, at some institutions primary angioplasty is favored. Randomized trials have shown that primary angioplasty is equal or superior to thrombolysis, while recent studies demonstrate that stent implantation improves the results of primary angioplasty. METHODS: Patients presenting with AMI were randomly assigned to primary stenting (n = 62) or accelerated t-PA (n = 61). The primary end point was the composite of death, reinfarction, stroke or repeat target vessel revascularization (TVR) for ischemia at six months. RESULTS: The primary end point was significantly reduced in the stent group compared with the accelerated t-PA group, 24.2% versus 55.7% (p < 0.001). The event rates for other outcomes in the stent group versus the t-PA group were as follows: mortality: 4.8% versus 3.3% (p = 1.00); reinfarction: 6.5% versus 16.4% (p = 0.096); stroke: 1.6% versus 4.9% (p = 0.36); recurrent unstable ischemia: 9.7% versus 26.2% (p = 0.03) and repeat TVR for ischemia: 14.5% versus 49.2% (p < 0.001). The median length of the initial hospitalization was four days in the stent group and seven days in the t-PA group (p < 0.001). CONCLUSIONS: Compared with accelerated t-PA, primary stenting reduces death, reinfarction, stroke or repeat TVR for ischemia. In centers where facilities and experienced interventionists are available, primary stenting offers an attractive alternative to thrombolysis.

Asunto(s)

Infarto del Miocardio/terapia , Stents , Terapia Trombolítica , Anciano , Angiografía Coronaria , Femenino , Fibrinolíticos/uso terapéutico , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Infarto del Miocardio/diagnóstico por imagen , Infarto del Miocardio/tratamiento farmacológico , Infarto del Miocardio/mortalidad , Oportunidad Relativa , Recurrencia , Stents/efectos adversos , Accidente Cerebrovascular/etiología , Tasa de Supervivencia , Terapia Trombolítica/efectos adversos , Activador de Tejido Plasminógeno/uso terapéutico , Resultado del Tratamiento

RESUMEN

Previously, we demonstrated that replication in restenotic coronary atherectomy specimens was an infrequent and modest event. In general, this data was interpreted with caution, as immunocytochemistry for the proliferating cell nuclear antigen (PCNA) was used to subjectively assess proliferation and most of the tissue specimens were resected more than 3 months after the initial interventional procedure. The purpose of the present study was to use a more sensitive method of detecting replication, in situ hybridization for histone 3 (H3) mRNA, to determine the replication profile of human directional atherectomy specimens. Restenotic directional coronary atherectomy specimens from lesions that had undergone an interventional procedure within the preceding 3 months were studied. In addition, larger atherectomy specimens from peripheral arterial lesions were assessed to ensure that pockets of replication were not being overlooked in the smaller coronary specimens. We found evidence for replication in tissue resected from 2/17 coronary and 9/12 peripheral artery restenotic lesions. In contrast, 3/11 specimens resected from primary lesions of peripheral arteries also expressed H3 mRNA. We estimated that the maximum percentage of cells that were replicating in restenotic coronary, restenotic peripheral and primary peripheral artery tissue slides to be <0.5, < or =1.2 and <0.01%, respectively. Replication was found in tissue specimens resected both early and late after a previous interventional procedure. For specimens with >15 replicating cells per slide we found high levels of focal replication. Therefore, cell replication, as assessed by the expression of H3 mRNA, was infrequent in restenotic coronary artery specimens, whereas peripheral restenotic lesions had more frequent and higher levels of replication regardless of the interval from the previous interventional procedure. For all specimens the percentage of cells that were replicating was low, however focal areas with relatively high replication indices were presented. Although replication was more abundant in restenotic lesions it does not appear to be a dominant event in the pathophysiology of restenosis.

Asunto(s)

Enfermedad de la Arteria Coronaria/patología , Enfermedad Coronaria/patología , Músculo Liso Vascular/patología , ARN Mensajero/análisis , Adulto , Anciano , Aterectomía , División Celular , Enfermedad de la Arteria Coronaria/cirugía , Técnicas de Cultivo , Endotelio Vascular/patología , Femenino , Histonas/genética , Humanos , Hibridación in Situ , Masculino , Persona de Mediana Edad , Músculo Liso Vascular/citología , Probabilidad , Recurrencia , Valores de Referencia , Sensibilidad y Especificidad

RESUMEN

BACKGROUND: The alpha4beta1 (or very late antigen-4 [VLA-4]) integrin is thought to play a role in inflammatory processes, mediating mononuclear leukocyte infiltration. The adventitial response to balloon injury is an important determinant of neointimal formation and arterial remodelling. OBJECTIVES: To determine whether the monoclonal antibody hHP1/2 directed against the human alpha4-integrin subunit decreases neoadventitial formation and subsequent luminal narrowing following balloon injury. DESIGN: Randomized, double-blind, placebo controlled study. SETTING: Tertiary care, Canadian university hospital vascular biology laboratory. ANIMALS AND METHODS: In 16 pigs, two coronary arteries were injured with an oversized balloon, while a third coronary artery was designated as an uninjured control vessel. One hour before balloon injury, 5 mg/kg of hHP1/2 was administered to eight animals, while another eight animals received an infusion of a saline placebo. Animals were killed three and 14 days following balloon injury. MAIN RESULTS: Administration of hHP1/2 resulted in an immediate decrease in circulating monocyte and lymphocyte counts. These parameters returned to normal within three days. There was a decrease in neoadventitial formation 14 days after arterial injury in pigs treated with hHP1/2 compared with controls (2.26+/-0.77 versus 3.42+/-1.01 mm, respectively, P=0.04). There was a loss of lumen area between days 3 (4.33+/-1.09 mm2) and 14 (3.09+/-0.38 mm2, P=0.02) after balloon injury in pigs treated with saline, but not in the pigs treated with hHP1/2. CONCLUSIONS: Administration of an antibody to the alpha4-integrin subunit is associated with less neoadventitial formation and less lumenal narrowing after balloon injury. This novel therapy may play an important role in modulating arterial remodelling and thereby may reduce restenosis following percutaneous coronary interventions in humans.

Asunto(s)

Angioplastia Coronaria con Balón , Anticuerpos Monoclonales/farmacología , Vasos Coronarios/lesiones , Integrinas/inmunología , Receptores Mensajeros de Linfocitos/inmunología , Túnica Íntima/lesiones , Animales , Vasos Coronarios/inmunología , Vasos Coronarios/patología , Displasia Fibromuscular/inmunología , Displasia Fibromuscular/patología , Displasia Fibromuscular/prevención & control , Humanos , Integrina alfa4beta1 , Integrinas/fisiología , Recuento de Linfocitos , Receptores Mensajeros de Linfocitos/fisiología , Porcinos , Túnica Íntima/inmunología , Túnica Íntima/patología

RESUMEN

Coronary atherectomy offers the intuitive advantage of removing tissue mass in order to improve blood flow. A second major benefit of atherectomy is the opportunity to study lesion tissue and make pathophysiological insights. The value of the latter cannot be over emphasized, as current animal models for the study of atherosclerosis and restenosis are fraught with limitations. In this review, we outline some of the key descriptive findings that have emerged from the study of atherectomy specimens. Specifically, we will focus on the role of smooth muscle cell proliferation, thrombus organization and matrix formation in primary atherosclerotic lesions, as well as restenotic lesions after balloon angioplasty and stenting.

Asunto(s)

Aterectomía Coronaria , Enfermedad de la Arteria Coronaria/fisiopatología , Vasos Coronarios/patología , Apoptosis , Vasos Coronarios/fisiopatología , Endotelio Vascular/patología , Humanos , Músculo Liso Vascular/patología , Recurrencia , Stents

RESUMEN

OBJECTIVES: Arterial remodeling has been suggested as the predominant factor in restenosis. However, the time course and morphometric factors that determine whether remodeling occurs remain unclear. We hypothesized that arterial remodeling does not occur in all arteries following balloon injury and is dependent on neoadventitial formation. METHODS: Using single (SI) and double (DI) balloon injury of Yorkshire porcine coronary arteries we examined changes in morphometry 3, 7, 14, 28 days following balloon injury. RESULTS: In both SI and DI arteries, the neoadventitia (NAD) area expanded by day 3 and was the first compartment to increase following injury. In SI arteries lumen area (LA) decreased between day 3 and 14 while in DI arteries, there was significantly less loss in LA. In SI arteries, contracture of the area circumscribed by the external elastic lamina (EEL), which occurred predominantly between day 7 and 14, accounted for 67% of the loss of LA. CONCLUSIONS: Accumulation of NAD appears to be the earliest change in the vessel wall following balloon injury of normal or previously injured arteries and precedes the growth of the I + M (intima and media). The predominant mechanism for lumenal narrowing following single balloon injury of a normal artery is remodeling. In contrast, remodeling does not occur in DI arteries, possibly due to differences in the degree of adventitial fibrosis of normal and injured arteries.

Asunto(s)

Angioplastia de Balón/efectos adversos , Enfermedad Coronaria/patología , Vasos Coronarios/lesiones , Cicatrización de Heridas , Actinas/análisis , Animales , Colágeno/análisis , Enfermedad Coronaria/metabolismo , Vasos Coronarios/metabolismo , Vasos Coronarios/patología , Inmunohistoquímica , Músculo Liso Vascular/química , Recurrencia , Porcinos , Factores de Tiempo

RESUMEN

Stenting of saphenous vein graft (SVG) lesions is associated with significant clinical events at late follow-up. We sought to determine predictors of clinical outcome after this procedure. One hundred twenty-eight balloon-expandable stents were implanted in the SVGs of 106 patients. Baseline clinical and angiographic characteristics were analyzed. All grafts, including those not stented, were scored for extent of disease involving the luminal surface of the graft, and for the presence of low profile lesions (< 50% graft stenosis) and/or high profile lesions (> or = 50% graft stenosis). The in-hospital success rate was 98.1%. Before discharge, no patient died, required bypass surgery, or had repeat angioplasty of the same graft. Follow-up was obtained on all the patients. At a median of 18 months, 15% had died, 17% had experienced myocardial infarction, 20% had required repeat bypass surgery, and 37% needed repeat angioplasty to either the same site or a different lesion. Event-free survival was recorded in only 44% of the patients. The cumulative Kaplan-Meier survival at 2.4 years was 78.7%. Using the Cox proportional hazards model, predictors of survival were the absence of a high profile lesion in any nonstented patent graft (p = 0.004), and the use of lipid-lowering agents at follow-up (p = 0.01). Stenting SVG lesions can be performed with a high degree of procedural success, but at long-term follow-up there is a high rate of cardiac events. The absence of a high profile lesion in any nonstented patent graft is the strongest predictor of survival.

Asunto(s)

Puente de Arteria Coronaria , Enfermedad Coronaria/cirugía , Vena Safena/trasplante , Stents , Angioplastia Coronaria con Balón , Angiografía Coronaria , Puente de Arteria Coronaria/efectos adversos , Puente de Arteria Coronaria/métodos , Enfermedad Coronaria/diagnóstico por imagen , Enfermedad Coronaria/patología , Femenino , Estudios de Seguimiento , Predicción , Oclusión de Injerto Vascular/diagnóstico por imagen , Oclusión de Injerto Vascular/patología , Oclusión de Injerto Vascular/prevención & control , Humanos , Hipolipemiantes/uso terapéutico , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Infarto del Miocardio/etiología , Modelos de Riesgos Proporcionales , Reoperación , Retratamiento , Vena Safena/patología , Tasa de Supervivencia , Resultado del Tratamiento

RESUMEN

The spatial correlation between arterial wall microvessels and the accumulation of atherosclerotic plaque is well documented. The role of these microvessels in the development of primary and restenotic lesions is not known. To investigate the effect of interventional procedures on arterial wall microvessels, we studied the adventitial microvascularity of porcine coronary arteries subjected to angioplasty. Twenty-two juvenile domestic swine were subjected to single or repeated (double) balloon angioplasty of the coronary arteries, with the interval between the first and second injury being 14 days. The number, density, and size of adventitial microvessels were measured 1 hour as well as 3, 7, 14, and 28 days after injury. One hour after single balloon injury, there were very few intact adventitial microvessels. Adventitial microvessel number, microvessel area density, and microvessel size were maximal 3 days after single (SI) and double (DI) injury but subsequently underwent progressive regression. Adventitial endothelial cell replication, as assessed by the incorporation of bromodeoxyuridine, was very low for the majority of arteries. Maximal endothelial cell replication indices were observed 3 days after SI and DI (eg, 12.0+/-3.3%). Early after SI the central arterial lumen area transiently increased, then renarrowed. The lumen area did not change after DI. Arterial remodeling occurred, as the accumulation of intimal and medial mass was correlated with expansion of the external elastic lamina. Adventitial microvessel area density was correlated with central arterial luminal area (R=0.34, P=0.04). The adventitial microvessel area density and the microvessel size index were greater late after DI compared with SI. These data indicate that adventitial angiogenesis occurs within 3 days after balloon injury and that regression of adventitial microvessels after SI corresponds with arterial narrowing. Changes in the adventitial microvasculature may be a component of arterial remodeling after balloon angioplasty.

Asunto(s)

Angioplastia Coronaria con Balón , Vasos Coronarios/fisiopatología , Neovascularización Fisiológica/fisiología , Angioplastia Coronaria con Balón/efectos adversos , Animales , Arterias/fisiopatología , Vasos Coronarios/lesiones , Vasos Coronarios/patología , Endotelio Vascular/patología , Microcirculación/fisiología , Músculo Liso Vascular/patología , Periodo Posoperatorio , Porcinos , Factores de Tiempo , Heridas Penetrantes/etiología , Heridas Penetrantes/patología , Heridas Penetrantes/fisiopatología

RESUMEN

OBJECTIVES: This study sought to assess the late clinical and angiographic outcomes of patients who received stents within the first week of acute myocardial infarction (AMI). BACKGROUND: Recent studies have demonstrated that stenting of the infarct-related artery is a useful adjunct to balloon angioplasty in patients with AMI. However, there are limited data on the late clinical and angiographic outcomes of these patients. METHODS: Between January 1994 and September 1995, 32 patients at our institution underwent stenting of the infarct-related artery within 1 week of AMI: 13 within 14 hours (evolving group) and 19 between days 2 and 7 (recent AMI group). Late clinical follow-up was obtained on all survivors. Quantitative angiographic measurements were recorded on the stented segments before stenting, immediately after stenting, and on the follow-up angiograms. RESULTS: At 13.1+/-6.4 months from the time of stenting, three patients died and three required repeat angioplasty, but no patient had reinfarction or required bypass surgery. At follow-up 26 (81%) of 32 patients remained free of major cardiac events; of these, 24 (92%) were free of angina. Repeat angiography performed at 10.8+/-7.5 months in 26 (87%) of 30 discharged patients showed that all infarct-related arteries were patent and the restenosis rate was low: 22% in the 13 patients with evolving AMI (<14 hours) and 12% in the 19 patients with recent AMI (days 2 through 7). CONCLUSION: In this study stenting of the infarct-related artery in patients with evolving and recent AMI was associated with a favorable late clinical outcome. Patency of the infarct-related artery was well maintained, and the restenosis rate was low.

Asunto(s)

Angiografía Coronaria , Infarto del Miocardio/cirugía , Stents , Angioplastia Coronaria con Balón , Anticoagulantes/uso terapéutico , Femenino , Fibrinolíticos/uso terapéutico , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/diagnóstico por imagen , Infarto del Miocardio/tratamiento farmacológico , Estudios Prospectivos , Recurrencia , Terapia Trombolítica , Resultado del Tratamiento

RESUMEN

BACKGROUND: Clues to the biology of coronary artery disease can be obtained through the study of proliferation in human coronary artery plaques. Previously, immunocytochemistry has been used to detect the proliferating cell nuclear antigen to demonstrate low levels of proliferation in directional coronary atherectomy tissue fragments resected from human coronary arteries. OBJECTIVES: To describe the proliferative profile of coronary artery tissue by using a more sensitive marker for cell replication. PATIENTS AND METHODS: Ten patients with unstable or stable angina pectoris underwent coronary atherectomy with a newer coronary atherectomy device, the Arrow-Fischell pullback atherectomy catheter. The histological features of the specimens were studied by using light microscopy, and cell proliferation was assessed with the use of in situ hybridization for the S phase-specific mRNA species, histone H3. RESULTS: Pullback coronary atherectomy immediately followed by percutaneous transluminal coronary angioplasty resulted in angiographic improvement in the lumen diameter in all but one patient, who required insertion of a stent. The atherectomy specimens consisted of a combination of atheromatous plaque and media. Four specimens had a small amount of adventitia. Five of the 10 specimens had no proliferating cells. Three specimens had between one and five proliferating cells per slide, while two specimens had relatively high proliferation indexes (2.5% and 4.2% of all cells per atherectomy cross-section). Both smooth muscle cells and macrophages were identified in areas with proliferating cells. The histology and proliferation profiles of the tissue resected from patients with stable and unstable angina were similar. CONCLUSIONS: Pullback atherectomy can be used effectively to debulk coronary artery lesions. By using a sensitive marker for cell replication, it was determined that the majority of the tissue specimens have low proliferation indexes.

Asunto(s)

Angioplastia Coronaria con Balón/métodos , Arteriosclerosis/cirugía , Aterectomía/métodos , Enfermedad Coronaria/cirugía , Antígeno Nuclear de Célula en Proliferación/inmunología , Angioplastia Coronaria con Balón/instrumentación , Arteriosclerosis/inmunología , Arteriosclerosis/patología , Aterectomía/instrumentación , Cateterismo Cardíaco/instrumentación , Angiografía Coronaria , Enfermedad Coronaria/inmunología , Enfermedad Coronaria/patología , Humanos

RESUMEN

Neointimal formation and arterial wall remodeling are pivotal causes of luminal narrowing in atherogenesis and restenosis. Arterial remodeling refers to a series of dynamic structural changes that arteries may undergo in response to various stimuli, including changes in blood flow and pressure, and acute injury. The biological mechanisms involved in arterial remodeling are poorly understood and are currently a main target for research. We have recently focused on the role of the arterial wall microcirculation (ie, vasa vasorum) in arterial remodeling after injury. In the past, a correlation between arterial wall neovascularization and the accumulation of arterial plaque has been documented; however, the dynamic role of these microvessels in arterial repair and luminal narrowing has not been examined. The type of arterial injury, the nature of the lesion that develops, and the arterial compartment in which angiogenesis occurs may determine the role of the vasa vasorum in arterial narrowing. In this review, we highlight the data that link arterial wall neovascularization with lesion formation and the process of arterial remodeling.

Asunto(s)

Arteriosclerosis/patología , Enfermedad Coronaria/prevención & control , Endotelio Vascular/patología , Neovascularización Patológica , Arterias , Endotelio Vascular/embriología , Endotelio Vascular/crecimiento & desarrollo , Humanos , Microcirculación/fisiología , Recurrencia , Vasa Vasorum/patología

RESUMEN

OBJECTIVES: Recent studies suggest that alterations in tissue thrombolysis as well as the inward migration of cells may be specific events that contribute to coronary artery narrowing after cardiac transplantation. Plasminogen activators and inhibitors play a central role in governing not only tissue thrombolysis, but also vascular cell migration. The purpose of this study was to examine arterial wall expression of the plasminogen activation system in coronary arteries during graft vascular disease initiation and progression. METHODS: Using in situ hybridization and immunocytochemistry, the expression patterns of uPA and PAI-1 in coronary arteries from cardiac allografts were compared to those of young individuals without disease. RESULTS: Both PAI-1 and uPA were over-expressed early after transplantation and as late as 27 months post grafting. Over-expression of these molecules preceded morphological evidence of graft vascular disease. Of special note was the adventitial expression of uPA and PAI-1 in microvessels and myofibroblasts. In contrast, the expression of uPA and PAI-1 in normal coronary arteries was confined to endothelial cells of the central lumen, as well as low levels of expression in intimal and medial smooth muscle cells. CONCLUSIONS: Despite morphologic similarities between normal and transplant coronary arteries, differences were noted in the vascular expression pattern of uPA and PAI-1. The exact role of these molecules in graft vascular disease requires further study; however, it is intriguing to consider that a local imbalance in the plasminogen system may contribute to arterial wall thrombosis and/or excessive cell migration and the genesis of complex vascular lesions.

Asunto(s)

Enfermedad Coronaria/metabolismo , Vasos Coronarios/química , Enfermedad Injerto contra Huésped/etiología , Trasplante de Corazón , Inhibidor 1 de Activador Plasminogénico/análisis , Activador de Plasminógeno de Tipo Uroquinasa/análisis , Adolescente , Adulto , Vasos Coronarios/enzimología , Expresión Génica , Enfermedad Injerto contra Huésped/metabolismo , Humanos , Inmunohistoquímica , Hibridación in Situ , Masculino , Inhibidor 1 de Activador Plasminogénico/genética , ARN Mensajero/análisis , Factores de Tiempo , Activador de Plasminógeno de Tipo Uroquinasa/genética

RESUMEN

Data on the feasibility, safety, and clinical outcome of intracoronary stenting in acute myocardial infarction (AMI) are limited. This study examined the immediate angiographic results and the early and late outcomes in 32 patients who had stenting during AMI. Coronary angiograms recorded at the time of stenting were reviewed with quantitative measurements obtained on the "target" coronary lesion before and after stenting. Immediate angiographic success was achieved in 30 patients (94%). The minimal luminal diameter increased from 0.36 +/- 0.37 to 2.58 +/- 0.41 mm (p<0.0001). Two patients died in the hospital. Of the remainder, none had reinfarction or required bypass surgery, whereas 2 required repeat coronary angioplasty for recurrent ischemia. Although thrombus at the infarct-related coronary lesion was initially detected in 41% of the patients, its presence was not associated with adverse procedural outcome. Only 1 patient had persistent thrombus after stenting, which resolved with intracoronary urokinase. At a mean follow-up of 6.1 +/- 4.1 months, there was 1 additional cardiac death, and no patient had AMI or required repeat coronary angioplasty or bypass; among the 29 survivors, 86% were free of angina. Thus, intracoronary stenting of the infarct-related artery in the setting of AMI is associated with excellent immediate angiographic success and a favorable clinical outcome, and remains an option even in the presence of thrombus.

Asunto(s)

Infarto del Miocardio/terapia , Stents , Adulto , Anciano , Angioplastia Coronaria con Balón , Constricción Patológica , Angiografía Coronaria , Trombosis Coronaria/complicaciones , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/complicaciones , Infarto del Miocardio/diagnóstico por imagen , Recurrencia , Estudios Retrospectivos , Insuficiencia del Tratamiento , Resultado del Tratamiento

RESUMEN

Transforming growth factor-beta (TGF-beta) plays an important role in vascular lesion formation and possibly the renarrowing process ("restenosis") that occurs after balloon angioplasty. Secreted in a latent form by most cells, TFG-beta requires enzymatic conversion before it is biologically active. TGF-beta-inducible gene h3 (beta ig-h3) is a novel molecule that is induced when cells are treated with TGF-beta1. This study examined the expression of beta ig-h3 in normal and diseased human vascular tissue. To determine the expression pattern of beta ig-h3 in human arteries, immunocytochemistry was performed on tissue sections from (1) normal internal mammary arteries, (2) the proximal left anterior descending coronary artery (with minimal intimal thickening) of 15 patients aged 18 to 40 years, (3) primary and restenotic coronary lesions from 7 patients, and (4) fresh directional atherectomy tissue from 11 patients. A polyclonal antibody consistently immunodetected beta ig-h3 protein in endothelial cells of all vascular tissue. In normal coronary arteries of young individuals, beta ig-h3 protein was absent from the intima and media but was found in the subendothelial smooth muscle cells of some arteries with modest intimal thickening. In diseased arteries beta ig-h3 protein was more abundant in the intima than the media. Restenotic coronary lesions tended to show higher levels of immunodetectable beta ig-h3 protein, especially in areas of dense fibrous connective tissue. Beta ig-h3 protein was immunodetected in the cytoplasm of plaque macrophages as well as smooth muscle and endothelial cells. By using in situ hybridization on fresh directional atherectomy specimens, we found beta ig-h3 mRNA to be overexpressed by plaque macrophages and smooth muscle cells. Nondiseased human internal mammary arteries also expressed beta ig-h3 mRNA in endothelial cells but not in the smooth muscle cells of the normal intima and media. These results document the expression of beta ig-h3 in diseased human arterial tissue and support the hypothesis that active TGF-beta plays a role in atherogenesis and restenosis.

Asunto(s)

Enfermedad Coronaria/patología , Factor de Crecimiento Transformador beta/análisis , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Animales , Células CHO/química , Enfermedad Coronaria/genética , Vasos Coronarios/química , Cricetinae , Femenino , Regulación de la Expresión Génica , Humanos , Macrófagos/química , Masculino , Arterias Mamarias/química , Músculo Liso Vascular/química , ARN Mensajero/análisis , Recurrencia , Factor de Crecimiento Transformador beta/genética

RESUMEN

The thrombospondins (TSP-1, -2, and -3) comprise a family of proteins that are homologous at the carboxy terminus but have unique sequences at the amino terminus that might be correlated with the regulation of cell behavior. To investigate the expression of TSP-1, -2, and -3 in endothelial cells, we examined developing murine blood vessels and human atherosclerotic plaques by in situ hybridization. The expression of TSP-1 was also characterized in cultured bovine aortic endothelial cells. Expression of TSP-2 was seen in the dorsal aorta as early as embryonic day 10; TSP-1 was not detected in endothelial cells until later stages, and TSP-3 was not apparent in the vasculature. In atherosclerotic specimens, TSP-1 mRNA was detected in many intraplaque microvessels and in the endothelium lining the atheromatous plaque; TSP-2 was absent from these regions. Cultured bovine aortic endothelial cells did not transcribe TSP-2 mRNA at detectable levels. There were high steady-state levels of TSP-1 mRNA in subconfluent bovine aortic endothelial cells before confluence and at the wound edge after injury of the cell monolayer, with maximal expression of TSP-1 in cultures at a time during which approximately 35% of the cells were in S phase. As the majority of these cells subsequently undergo mitosis, these data are consistent with TSP-1 as an inhibitor of endothelial cell proliferation that functions in G1. These results support the conclusion that, despite sequence homology, the TSPs have distinct functions in vascular biology.

Asunto(s)

Endotelio Vascular/metabolismo , Glicoproteínas de Membrana/metabolismo , Animales , Arteriosclerosis/metabolismo , Arteriosclerosis/patología , Vasos Sanguíneos/embriología , Vasos Sanguíneos/metabolismo , Bovinos , Moléculas de Adhesión Celular/metabolismo , Recuento de Células , División Celular , Células Cultivadas , Embrión de Mamíferos/metabolismo , Endotelio Vascular/citología , Endotelio Vascular/patología , Femenino , Humanos , Ratones , Trombospondinas

RESUMEN

Chlamydia pneumoniae is a common respiratory pathogen. Recent studies have demonstrated the presence of C. pneumoniae in coronary and aortic atherosclerotic lesions. To study the role of C. pneumoniae in atherosclerosis, we investigated the susceptibilities of three different cells of the human vascular wall to infection with C. pneumoniae AR-39. These cell types were endothelial cells, smooth muscle cells, and macrophages derived from peripheral blood monocytes. Infection was assessed by using a direct fluorescent antibody to assess inclusion counts. Duplicate cell samples were harvested 3 days postinfection and were passed in HL cells, a susceptible human epithelial cell line, to determine if infectious organisms were produced. Endothelial cells, smooth muscle cells, and macrophages were capable of supporting C. pneumoniae growth in vitro. These results showed that three different cell types known to be important in atherogenesis are susceptible to infection with C. pneumoniae.

Asunto(s)

Infecciones por Chlamydia/microbiología , Chlamydophila pneumoniae/patogenicidad , Endotelio Vascular/microbiología , Macrófagos/microbiología , Músculo Liso Vascular/microbiología , Células Cultivadas , Humanos , Virulencia