Update on Trials & Devices for Endovascular Management of the Ascending Aorta and Arch.

Thoracic endovascular aortic repair (TEVAR) may treat a variety of acute and chronic aortic diseases as described in several articles in this issue of TVIR. A major challenge to endovascular treatment in the thoracic aorta is disease involving or in close proximity to the aortic valve, coronary arteries, or aortic arch branch vessels. Disease involving the ascending aorta in particular has significant limitations based on its distance from the aortic root. The left subclavian artery (LSA) can be covered in the emergent setting to ensure an adequate landing zone, but patients may require later surgical revascularization, and any coverage of the carotid arteries would require definite pre-endograft revascularization. Open surgical repair continues to have high morbidity and mortality rates in the acute setting, and endovascular therapy is preferred if feasible. Ad hoc modifications of current endografts to maintain arch vessel patency include placement of chimney/snorkel stents or custom fenestrations. However, there is a need for commercially available "off-the-shelf" ascending arch stent-grafts and branched stent-grafts that allow for complete endovascular repair of the aortic arch. This review will focus on devices under investigation for the treatment of pathologies involving the ascending aorta and aortic arch.

Calcification of Human Saphenous Vein Associated with Endothelial Dysfunction: A Pilot Histopathophysiological and Demographical Study.

While the pathophysiology and clinical significance of arterial calcifications have been studied extensively, minimal focus has been placed on venous calcification deposition. In this study, we evaluated the association between calcium deposition in human saphenous vein (HSV), endothelial function, and patient demographic risk factors. Fifty-four HSV segments were collected at the time of coronary artery bypass graft (CABG) surgery. The presence or absence of calcium deposits was visualized using the Von Kossa staining method. Endothelial function was determined by measuring muscle tissue contraction with phenylephrine and relaxation with carbachol in a muscle bath. Additional segments of vein underwent histologic evaluation for preexisting intimal thickness and extracellular matrix (ECM) deposition. Patient demographics data were obtained through our institution's electronic medical record, with patient consent. Calcium was present in 16 of 54 samples (29.6%). Veins with calcium deposits had significantly greater intimal-to-medial thickness ratios (p = 0.0058) and increased extracellular collagen deposition (p = 0.0077). Endothelial relaxation was significantly compromised in calcified veins vs. those without calcium (p = 0.0011). Significant patient risk factors included age (p = 0.001) and preoperative serum creatinine (p = 0.017). Calcified veins can be characterized as having endothelial dysfunction with increased basal intimal thickness and increased ECM deposition. Patient risk factors for calcium deposits in veins were similar to those for arteries, namely, advanced age and kidney disease. Further studies are needed to determine the effect of preexisting vein calcification on short- and long-term graft patency.

Heat Shock-Related Protein 20 Peptide Decreases Human Airway Constriction Downstream of ß2-Adrenergic Receptor.

Severe bronchospasm refractory to ß-agonists is a challenging aspect of asthma therapy, and novel therapeutics are needed. ß-agonist-induced airway smooth muscle (ASM) relaxation is associated with increases in the phosphorylation of the small heat shock-related protein (HSP) 20. We hypothesized that a transducible phosphopeptide mimetic of HSP20 (P20 peptide) causes relaxation of human ASM (HASM) by interacting with target(s) downstream of the ß2-adrenergic receptor (ß2AR) pathway. The effect of the P20 peptide on ASM contractility was determined in human and porcine ASM using a muscle bath. The effect of the P20 peptide on filamentous actin dynamics and migration was examined in intact porcine ASM and cultured primary HASM cells. The efficacy of the P20 peptide in vivo on airway hyperresponsiveness (AHR) was determined in an ovalbumin (OVA) sensitization and challenge murine model of allergic airway inflammation. P20 peptide caused dose-dependent relaxation of carbachol-precontracted ASM and blocked carbachol-induced contraction. The ß2AR inhibitor, (±)-1-[2,3-(dihydro-7-methyl-1H-inden-4-yl)oxy]-3-[(1-methylethyl)amino]-2-butanol hydrochloride (ICI 118,551), abrogated isoproterenol but not P20 peptide-mediated relaxation. The P20 peptide decreased filamentous actin levels in intact ASM, disrupted stress fibers, and inhibited platelet-derived growth factor-induced migration of HASM cells. The P20 peptide treatment reduced methacholine-induced AHR in OVA mice without affecting the inflammatory response. These results suggest that the P20 peptide decreased airway constriction and disrupted stress fibers through regulation of the actin cytoskeleton downstream of ß2AR. Thus, the P20 peptide may be a potential therapeutic for asthma refractory to ß-agonists.