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Here we investigated how a coating of intravascular balloon with paclitaxel (drug-coated balloon; DCB, Freeway™) impacted porcine peripheral artery vascular function and remodeling. Domestic swine (n = 54) underwent percutaneous overstretch balloon dilation of femoral and iliac arteries, controlled by angiography and optical coherence tomography (OCT). Paclitaxel tissue uptake was measured at 1 h and 1, 3, and 9 days post-dilation. At these time-points and at 32 ± 2 days, vascular function of the dilated arteries was assessed using the organ chamber model. Neointimal growth and remodeling indices were determined using OCT and histology at 32 ± 2 days. Intima and media fibrosis were quantified by picrosirius red staining. Post-inflation femoral artery tissue drug levels were 460 ± 214, 136 ± 123, 14 ± 6, and 0.1 ± 0.1 ng/mg at 1 h and 1, 3, and 9 days, respectively. Compared to plain balloon, Freeway™ resulted in a significantly smaller neointimal area (P < 0.05), less tunica intima (8.0 ± 5.4 vs 14.2 ± 4.7 %) and media fibrosis (15.6 ± 7.7 vs 24.5 ± 5.4 %), and less femoral artery constrictive remodeling (remodeling index: 1.08 ± 0.08 vs 0.94 ± 0.08). The DCB was associated with significantly increased vasoconstrictor tone and endothelium-dependent vasodilation impairment shortly after post-overstretch injury. Overall, DCB dilation of peripheral arteries resulted in high drug uptake into arterial tissue. Compared with the plain balloon, the DCB was associated with decreased vessel wall fibrosis after balloon overstretch injury, and reduced degrees of constrictive remodeling and neointimal hyperplasia.

Purpose of Review: Myocardial infarction (MI) leading to heart failure displays an important cause of death worldwide. Adequate restoration of blood flow to prevent this transition is a crucial factor to improve long-term morbidity and mortality. Novel regenerative therapies have been thoroughly investigated within the past decades., Recent Findings: Increased angiogenesis in infarcted myocardium has shown beneficial effects on the prognosis of MI; therefore, the proangiogenic capacity of currently tested treatments is of specific interest. Molecular imaging to visualize formation of new blood vessels in vivo displays a promising option to monitor proangiogenic effects of regenerative substances., Summary: Based on encouraging results in preclinical models, molecular angiogenesis imaging has recently been applied in a small set of patients. This article reviews recent literature on noninvasive in vivo molecular imaging of angiogenesis after MI as an integral part of cardiac regeneration., Competing Interests: Compliance with Ethics Standards Conflict of Interest The authors declare that they have no conflict of interest. Human and Animal Rights and Informed Consent This article does not contain any studies with human or animal subjects performed by any of the authors.

Activated protein C (APC), an endogenous protein, inhibits inflammation and thrombosis and interrupts the coagulation cascade. Here, we investigated the effect of human recombinant APC on the development of neointimal hyperplasia in porcine coronary arteries. Yukon Choice bare metal stents were coated with 2.6 µg APC/mm(2). Under general anesthesia, APC-coated and bare stents were implanted in the left anterior descending and circumflex coronary arteries of 10 domestic pigs. During the 4-week follow-up, animals were treated with dual antiplatelet therapy and neointimal hyperplasia was evaluated via histology. Scanning electron microscopy indicated successful but unequal coating of stents with APC; nearly complete drug release occurred within 4 h. Enzyme-linked immunosorbent assay revealed that intracoronary stent implantation rapidly increased the levels of monocyte chemoattractant protein-1, an effect that was inhibited by APC release from the coated stent. Fibrin deposition and adventitial inflammation were significantly decreased 1 month after implanting APC-coated stents versus bare stents, paralleled by significantly smaller neointimal area (0.98 ± 0.92 vs. 1.44 ± 0.91 mm(2), P = 0.028), higher lumen area (3.47 ± 0.94 vs. 3.06 ± 0.91 mm(2), P = 0.046), and lower stenosis area (22.2 ± 21.2% vs. 32.1 ± 20.1%, P = 0.034). Endothelialization was complete with APC-coated but not bare (90%) stents. P-selectin immunostaining revealed significantly fewer activated endothelial cells in the neointima in the APC group (4.6 ± 1.9 vs. 11.6 ± 4.1%, P < 0.001). Thus, short exposure of coronary arteries to APC reduced inflammatory responses, neointimal proliferation, and in-stent restenosis, offering a promising therapy to improve clinical outcomes of coronary stenting. However, coating stents with APC for prolonged, controlled drug release remains technically challenging.