Repairing thoracoabdominal aortic aneurysms poses substantial risks, particularly when the entire thoracoabdominal aorta (extent II) is replaced. Nonetheless, our data suggest that thoracoabdominal aortic aneurysm repair, when performed at an experienced center, can produce respectable outcomes.

The rapid development of angiogenic growth factor therapy for patients with advanced ischemic heart disease over the last 5 years offers hope of a new treatment strategy based on generation of new blood supply in the diseased heart. However, as the field of therapeutic coronary angiogenesis is maturing from basic and preclinical investigations to clinical trials, many new and presently unresolved issues are coming into focus. These include in-depth understanding of the biology of angiogenesis, selection of appropriate patient populations for clinical trials, choice of therapeutic end points and means of their assessment, choice of therapeutic strategy (gene versus protein delivery), route of administration, and the side effect profile. The present article presents a summary statement of a panel of experts actively working in the field, convened by the Angiogenesis Foundation and the Angiogenesis Research Center during the 72nd meeting of the American Heart Association to define and achieve a consensus on the challenges facing development of therapeutic angiogenesis for coronary disease.

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Internal thoracic arteries (ITAs) should be used to bypass the left anterior descending (LAD) artery when bypass of the LAD is indicated (class of recommendation [COR] I, level of evidence [LOE] B). As an adjunct to left internal thoracic artery (LITA), a second arterial graft (right ITA or radial artery [RA]) should be considered in appropriate patients (COR IIa, LOE B). Use of bilateral ITAs (BITAs) should be considered in patients who do not have an excessive risk of sternal complications (COR IIa, LOE B). To reduce the risk of sternal infection with BITA, skeletonized grafts should be considered (COR IIa, LOE B), smoking cessation is recommended (COR I, LOE C), glycemic control should be considered (COR IIa, LOE B), and enhanced sternal stabilization may be considered (COR IIb, LOE C). As an adjunct to LITA to LAD (or in patients with inadequate LITA grafts), use of a RA graft is reasonable when grafting coronary targets with severe stenoses (COR IIa, LOE: B). When RA grafts are used, it is reasonable to use pharmacologic agents to reduce acute intraoperative and perioperative spasm (COR IIa, LOE C). The right gastroepiploic artery may be considered in patients with poor conduit options or as an adjunct to more complete arterial revascularization (COR IIb, LOE B). Use of arterial grafts (specific targets, number, and type) should be a part of the discussion of the heart team in determining the optimal approach for each patient (COR I, LOE C).

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Author Contributions: Drs Mortus and Rosengart had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Vascular endothelial growth factor (VEGF) receptorFlk-1/KDR in endothelial cells is activated during vasculogenesis and angiogenesis upon ligand-receptor interaction. Activated Flk-1/KDR has been shown to recruit Src homology 2 domain-containing signaling molecules that are known to serve as links to the activation of the mitogen-activated protein (MAP) kinase signaling pathway. To define the functional significance of phosphatidylinositol (PI) 3-kinase in VEGF signaling, we have examined its role in human umbilical vein endothelial cell (HUVEC) cycle progression. We show herein that p85, the regulatory subunit of PI 3-kinase, is constitutively associated with Flk-1/KDR. The treatment of HUVECs with VEGF promoted tyrosine autophosphorylation of Flk-1/KDR and also induced phosphorylation of p85. This was followed by an increase in the PI 3-kinase activity, which was sensitive to wortmannin, a potent PI 3-kinase inhibitor. VEGF also induced a striking activation of MAP kinase in a time-dependent manner. Inhibition studies with both a dominant-negative p85 mutant and the PI 3-kinase inhibitor, wortmannin, were employed to show for the first time that VEGF-stimulated PI 3-kinase modulates MAP kinase activation and nuclear events such as transcription from c-fos promoter and entry into the synthesis (S)-phase. Our data demonstrate the importance of PI 3-kinase as a necessary signaling component of VEGF-mediated cell cycle progression.