Endothelial expression of Akt is responsible for tumor responsiveness to rapamycin. We demonstrate that expression of phosphorylated S6 is elevated in specimens. Our findings provide a rationale for clinical trials of rapamycin on Sturge-Weber or Klippel-Trenaunay-Weber patients.

BackgroundProgenitor cells (PCs) are mobilized in response to vascular injury to effect regeneration and repair. Recruitment of PCs requires intact nitric oxide (NO) synthesis by endothelial cells, and their number and activity correlate with cardiovascular disease risk burden and future outcomes. Whereas cardiovascular vulnerability exhibits a robust circadian rhythm, the 24‐hour variation of PCs and their inter‐relation with vascular function remain unknown. We investigated the circadian variation of PCs and vascular function with the hypothesis that this will parallel the pattern observed for cardiovascular events (CVEs).Methods and ResultsIn 15 healthy subjects (9 men, 37±16 years), circulating PCs and vascular function were measured at 8 am, noon, 4 pm, 8 pm, midnight, 4 am (only PCs counts), and 8 am the following day. Circulating PCs were enumerated as mononuclear cells (MNCs; CD45med) that express CD34 as well as CD133, and their activity was assessed as the number of colonies formed by culturing MNCs. Vascular function was evaluated by measurement of endothelium‐dependent, flow‐mediated vasodilation (FMD) of the brachial artery and tonometry‐derived indices of arterial stiffness. Higher CD34+ and CD34+/CD133+ cell counts were observed at 8 pm than any other time of the day (P‐ANOVA=0.038 and <0.001; respectively) and were lowest at 8 am. PC colony formation was highest at midnight (P‐ANOVA=0.045) and lowest in the morning hours. FMD was highest at midnight and lowest at 8 am and 8 pm, and systemic arterial stiffness was greatest at 8 am and lowest at 4 pm and midnight (P‐ANOVA=0.03 and 0.01; respectively).ConclusionA robust circadian variation in PC counts and vascular function occurs in healthy humans and both exhibit an unfavorable profile in the morning hours that parallels the preponderance of CVEs at these times. Whether these changes are precipitated by awakening and time‐dependent physical activity or governed by the endogenous circadian clock needs to be further investigated.

Pseudoaneurysm of the mitral-aortic intervalvular fibrosa is a rare but serious sequela of endocarditis or valve replacement surgery. Because open-heart surgery is a high-risk treatment option, alternative methods are sought. We present the case of a 77-year-old man with a noninfected mechanical mitral valve whose pseudoaneurysm was repaired by introducing an occluder device into the defect by a transapical approach. Upon follow-up imaging, the defect was successfully closed. We conclude that percutaneous closure of pseudoaneurysm of the mitral-aortic intervalvular fibrosa is a viable alternative to surgery and that a transapical approach is an appropriate method of access.

We report the fatal course of a left atrial myxoma: its systemic embolization to the coronary, cerebral, renal, and peripheral vascular beds in a 39-year-old W hen a patient presents with simultaneous vascular insults that involve multiple organ systems, a catastrophic clinical outcome can result. We report the case of a patient who had symptoms of systemic embolization, and we discuss the presentation, recognition, and treatment of the left atrial myxoma that was responsible. Case ReportA 39-year-old black woman was found unresponsive and in respiratory distress outside her home. According to her family, she had felt fatigued over the past 2 months and had occasionally reported fevers and night sweats. She had been taking oral contraceptive pills and smoked half a pack of cigarettes per day. Her personal and family medical histories yielded nothing else of note.Upon evaluation by emergency medical personnel, the patient was unconscious, tachypneic, and displaying possible seizure activity. In the emergency department, the patient was comatose with a Glasgow coma scale of 5, a temperature of 37 °C, a blood pressure of 117/77 mmHg, a heart rate of 133 beats/min, a respiratory rate of 30 breaths/min, and an oxygen saturation of 76% on room air. She was immediately intubated. A 12-lead electrocardiogram revealed 2-to 4-mm ST-segment elevation in the lateral leads, consistent with acute ST-elevation myocardial infarction (STEMI). Pertinent laboratory values included a cardiac troponin I level of 1.6 ng/mL, a white blood cell count of 13,800/µL, and an international normalized ratio of 1.21. The patient was anuric. A chest radiograph showed a normal cardiac silhouette with bilateral pulmonary edema. Aspirin (325 mg) was administered through a nasogastric tube, and an intravenous heparin drip was initiated. The diagnosis was cardiac arrest secondary to STEMI. A noncontrast computed tomographic scan of the patient's head was performed, and she was sent for emergent cardiac catheterization.Femoral arterial access was difficult to achieve in either groin because of the aspiration of thrombotic material. A 4F sheath was finally placed in the right femoral artery; the access sheath thrombosed twice during the procedure, necessitating the aspiration of large amounts of dark-red thrombus. Coronary angiograms obtained with use of 4F catheters showed abrupt thrombotic occlusion of the proximal-to-mid left anterior descending coronary artery, first diagonal branch, and proximal-to-mid left circumflex coronary artery (Fig. 1). The right coronary artery was angiographically normal. The occlusions were not suitable for catheter aspiration, balloon angioplasty, or stenting. A left ventriculogram showed a left ventricular ejection fraction (LVEF) of 0.30 and akinesis of the anterolateral, inferolateral, and apical walls. The computed tomographic report, received during the cardiac catheterization procedure, noted a large, acute embolic infarct in the region of the left middle cerebral artery. In view of the substantial thrombotic...

Studies investigating endothelial progenitor cell levels and cardiovascular (CVD) risk and outcomes have yielded contradictory information based on the assays employed. Culture assays of early ``angiogenic” endothelial cells differ from the late outgrowth ``proliferative” ones. We hypothesized that the number of colonies, representing the circulating pool of endothelial precursors, will be significantly stimulated by the presence of CVD and risk factors (RF). Methods We performed an ``intermediate” duration assay where peripheral blood mononuclear cells were cultured on fibronectin plates for 7 days and the number of colonies with endothelial-type cells at their periphery were counted by the same technician in all subjects. We sampled 420 subjects who either: were healthy and free of RF (n = 36, age = 47 ± 10), had metabolic syndrome, overt diabetes, or increased carotid thickness (n = 131, age = 59 ± 10), had coronary artery disease (n = 206, age = 61 ± 10), or peripheral vascular disease (n = 45, age = 64 ± 8). Results Endothelial precursor colony counts were lowest in the healthy subjects, higher in patients with RF, and highest in those with CVD (Figure ). These differences persisted after correcting for age. Conclusion Our data unequivocally demonstrates that the numbers of cultured endothelial colonies, utilizing an intermediate duration assay, are stimulated by the presence of risk factors, sub-clinical disease and overt CVD. This illustrates the presence of a reparative or compensatory regenerative response by endothelial progenitors to vascular injury. Whether an inadequate repair response is associated with increased risk needs to be further studied.