Neovascularization in human atherosclerosis.

In the absence of disease, microvessels provide vessel wall nutrients to the tunica media, while the intima is fed by oxygen diffusion from the lumen. As disease evolves and the tunica intima thickens, oxygen diffusion is impaired, and microvessels become the major source for nutrients to the vessel wall. Microvessels serve as a port of entry for inflammatory cells, from the systemic circulation to the nascent atherosclerotic lesion. As disease progress, microvessels also play a role in intraplaque hemorrhage, lipid core expansion, and plaque rupture. In addition, microvessels are also involved in stent restenosis, and plaque regression. Therefore, microvessels are a pivotal component of atherosclerosis, and proper patient risk-stratification in the near future may include the detection of increased neovascularization in atherosclerotic lesions. This review divided in two parts summarizes the current understanding of atherosclerosis neovascularization, starting with the normal anatomy and physiology and progressing to more advanced stages of the disease. We will review the structure and function of vasa vasorum in health and disease, the mechanisms responsible for the angiogenic process, the role of the immune system, including inflammation and Toll-like receptors, and the pathology of microvessels in early atherosclerotic plaques. Furthermore, the review addresses the advanced stages of atherosclerosis, summarizing the progressive role for microvessels during disease progression, red blood cell extravasation, lipid core expansion, plaque rupture, healing, repair, restenosis, and disease regression, offering the clinician a state-of-the-art, "bench to bedside" approach to neovascularization in human atherosclerosis.

Metabolic syndrome and diabetic atherothrombosis: implications in vascular complications.

Metabolic syndrome is characterized by the clustering of a number of metabolic abnormalities in the presence of underlying insulin resistance with a strong association with diabetes and cardiovascular disease morbidity and mortality. The disorder is defined in different ways, but the pathophysiology is attributable to insulin resistance. An increased release of free fatty acids (FFAs) from adipocytes block insulin signal transduction pathway, induce endothelial dysfunction due to increased reactive oxygen species (ROS) generation and oxidative stress. Dyslipidemia, associated with high levels of triglycerides and low concentrations of high density lipoproteins (HDLs), contributes to a proinflammatory state. Inflammation, the key pathogenic component of atherosclerosis, promotes thrombosis, a process that underlies acute coronary event and stroke. Tissue factor, a potent trigger of the coagulation cascade, is increased in diabetes with poor glycemic control. Therapeutic lifestyle changes (weight loss and physical activity) along with pharmacological interventions are recommended to prevent the complications of metabolic syndrome. In addition to statins, metformin, blood pressure lowering medications, interventions to increase HDLs are other important approaches to decrease the risk of cardiovascular disease. Furthermore, the peroxisome proliferator activated receptor (PPAR)-alpha and gamma agonists are potent anti-inflammatory and anti-atherogenic agents that could both improve insulin sensitivity and the long-term cardiovascular risk. In this review we focus on the molecular and pathophysiological basis of metabolic syndrome, which augments diabetes (insulin resistance) and the contribution of neovascularization in the plaque progression in diabetes, leading to rupture and coronary thrombosis.

Atherosclerosis neovascularization and imaging.

Neovascularization in atherosclerotic plaques is particularly prominent in complicated lesions, and has been recently identified as a marker of plaque vulnerability. This observation has led to a growing interest in the development of imaging techniques with the ability to visualize and quantify the extent of plaque neovascularization. Such feature may play an important role in identifying those lesions more prone to destabilization and rupture, and in the guidance and monitoring of therapeutic interventions. Several modalities have emerged as potential candidates for imaging neovessels in atherosclerotic lesions. They include magnetic resonance imaging, x-ray computed tomography, positron emission tomography, single photon emission computed tomography, ultrasound, or near-infrared optical imaging. These techniques differ in their achievable spatial and temporal resolution, availability, cost, reproducibility, degree of intrusiveness, capability to image atherosclerotic plaques in various vascular territories and ability to discern different plaque components, specifically the presence of neovessels. Molecular imaging, a rapidly evolving multidisciplinary field devoted to the visualization of specific physiopathologic processes at the cellular or molecular level, appears particularly well suited for this purpose because of its ability to target and visualize individual molecules specific to neoangiogenesis. In this manuscript we will review current evidence on the potential application of the various modalities, with a particular emphasis in molecular imaging.

An unusual presentation of metastatic colon cancer to the lung.

A 75-year-old man with a history of resected colon carcinoma presented to his primary care physician because of a new onset of coughing. The patient had expectorated a small piece of solid tissue; pathologic examination of the tissue found it to be consistent with metastatic colon adenocarcinoma. After further work-up, a right upper lobectomy was performed. The surgical specimen removed during the lobectomy showed a tumor that was histologically identical to the patient's prior colonic primary tumor.

Repair of coarctation with resection and extended end-to-end anastomosis.

BACKGROUND: Our surgical strategy for infant coarctation changed from subclavian flap aortoplasty to resection with extended end-to-end anastomosis in 1991. The purpose of this review was to evaluate the results of that strategy. METHODS: From 1991 through 1997, 55 infants underwent repair of coarctation of the aorta using resection with extended end-to-end anastomosis. Isolated coarctation of the aorta was present in 26 patients, 20 patients had a ventricular septal defect, and 9 patients had other associated intracardiac lesions. Mean age at surgery was 0.20+/-0.24 years (median, 21 days). In 34 patients (62%), arch reconstruction was performed through a left thoracotomy. Twenty patients (36%) had median sternotomy with simultaneous repair of coarctation of the aorta and intracardiac repair of associated lesions. One patient had recoarctation repair through a median sternotomy. All coarctation and ductal tissue was resected and the anastomosis was constructed starting opposite the left carotid artery with running polypropylene suture. RESULTS: There was one early death 26 days after coarctation of the aorta and ventricular septal defect repair in a child on extracorporeal membrane oxygenation for meconium aspiration and 2 late deaths owing to pneumonia and pulmonary hypertension (1) and interventricular hemorrhage (1). There were no instances of paraplegia. Follow-up in survivors ranges from 10 to 76 months (mean, 39.8+/-17.2 months). Recoarctation has developed in 2 patients, who have had successful balloon dilation 6 and 14 months after the operation. This yields a low recoarctation rate of 3.6%. CONCLUSIONS: Resection with extended end-to-end anastomosis yields a low mortality and particularly a low recoarctation rate and is our procedure of choice for infants with coarctation of the aorta.

Surgical repair of the congenitally malformed mitral valve in infants and children.

BACKGROUND: Mitral valve remodeling techniques were applied to 26 infants and children (mean age, 6.0 years, range, 0.4 to 15.9 years) with various forms of congenital mitral valve disease over a 7-year period. Patients with atrioventricular canal, L-transposition and single ventricle were excluded. Intraoperative transesophageal echocardiography (TEE) was utilized to assess the repair and guide the need for immediate intervention. METHODS: Twenty-one patients had mitral regurgitation: 10 with cleft anterior mitral leaflet, 7 with annular dilatation, 1 with normal leaflets with an obstructing cord, 2 with prolapsed leaflets and elongated cords, and 1 with restricted leaflet motion, normal papillary muscles, and shortened cords. Of the 5 mitral stenosis patients, 3 had supravalvular mitral ring, 1 had midvalvular mitral ring, and 1 had a parachute valve. Three of the mitral stenosis patients had additional stenotic lesions. Concurrent repair of associated lesions was performed in 21 patients (78%). RESULTS: Operative mortality was 3.8% (n = 1). There were no late deaths. Immediate rerepair in 4 patients resulted in improved function. All mitral stenosis patients improved. A total of 20 mitral regurgitation patients (95%) improved; 1 required mitral valve replacement. Mean follow-up is 31 months (range, 2 to 81 months). All patients are in New York Heart Association functional class I or II. CONCLUSIONS: Mitral valve repair can be successfully performed in infants and children with excellent short- and midterm results. Assessment using transesophageal echocardiography can guide the necessity for immediate rerepair to achieve improved function.