Resveratrol-Coated Balloon Catheters in Porcine Coronary and Peripheral Arteries.

Angioplasty aiming at vascular dilatation causes endothelial denudation and induces complex inflammatory responses that affect vascular healing, including delayed reendothelialization and excessive neointima proliferation. Resveratrol is known for multiple beneficial effects on the vessel wall after systemic treatment or sustained release from a stent. It is also used as an additive on drug-coated balloon catheters (DCB). In this study, the effect of a single dose of resveratrol, three days to four weeks after administration as a balloon coating during angioplasty, was investigated. Sixteen pigs underwent angioplasty with resveratrol-coated or uncoated balloon catheters in coronary and peripheral arteries. Vessels were overstretched by approximately 20% to enhance vessel wall injury and to produce persistent vessel wall irritation. A significantly reduced number of micro vessels and macrophages in the adventitia, as well as an improved reendothelialization of the vessel lumen, were observed in resveratrol-treated peripheral arteries. The coronaries had a much higher injury score compared to peripheral vessels. Resveratrol-dependent reduction of macrophages, micro vessels or acceleration of reendothelialization was not evident in the coronary vessels. Additionally, no significant effect on neointima proliferation and inflammation score in either vessel territory was observed as a result of resveratrol treatment. In conclusion, the results suggest that resveratrol diminishes the inflammatory response and promotes vascular healing in peripheral arteries. These same effects are absent in more severely injured coronary arteries.

Protective Function of Ahnak1 in Vascular Healing after Wire Injury.

AIM: Vascular remodeling following injury substantially accounts for restenosis and adverse clinical outcomes. In this study, we investigated the role of the giant scaffold protein Ahnak1 in vascular healing after endothelial denudation of the murine femoral artery. METHODS: The spatiotemporal expression pattern of Ahnak1 and Ahnak2 was examined using specific antibodies and real-time quantitative PCR. Following wire-mediated endothelial injury of Ahnak1-deficient mice and wild-type (WT) littermates, the processes of vascular healing were analyzed. RESULTS: Ahnak1 and Ahnak2 showed a mutually exclusive vascular expression pattern, with Ahnak1 being expressed in the endothelium and Ahnak2 in the medial cells in naïve WT arteries. After injury, a marked increase of Ahnak1- and Ahnak2-positive cells at the lesion site became evident. Both proteins showed a strong upregulation in neointimal cells 14 days after injury. Ahnak1-deficient mice showed delayed vascular healing and dramatically impaired re-endothelialization that resulted in prolonged adverse vascular remodeling, when compared to the WT littermates. CONCLUSION: The large scaffold and adaptor proteins Ahnak1 and Ahnak2 exhibit differential expression patterns and functions in naïve and injured arteries. Ahnak1 plays a nonredundant protective role in vascular healing.

In vivo biocompatibility assessment of poly (ether imide) electrospun scaffolds.

Poly(ether imide) (PEI), which can be chemically functionalized with biologically active ligands, has emerged as a potential biomaterial for medical implants. Electrospun PEI scaffolds have shown advantageous properties, such as enhanced endothelial cell adherence, proliferation and low platelet adhesion in in vitro experiments. In this study, the in vivo behaviour of electrospun PEI scaffolds and PEI films was examined in a murine subcutaneous implantation model. Electrospun PEI scaffolds and films were surgically implanted subcutaneously in the dorsae of mice. The surrounding subcutaneous tissue response was examined via histopathological examination at 7 and 28 days after implantation. No serious adverse events were observed for both types of PEI implants. The presence of macrophages or foreign body giant cells in the vicinity of the implants and the formation of a fibrous capsule indicated a normal foreign body reaction towards PEI films and scaffolds. Capsule thickness and inflammatory infiltration cells significantly decreased for PEI scaffolds during days 7-28 while remaining unchanged for PEI films. The infiltration of cells into the implant was observed for PEI scaffolds 7 days after implantation and remained stable until 28 days of implantation. Additionally some, but not all, PEI scaffold implants induced the formation of functional blood vessels in the vicinity of the implants. Conclusively, this study demonstrates the in vivo biocompatibility of PEI implants, with favourable properties of electrospun PEI scaffolds regarding tissue integration and wound healing. Copyright © 2015 John Wiley & Sons, Ltd.

Combinatorial G-CSF/AMD3100 treatment in cardiac repair after myocardial infarction.

AIMS: Several studies suggest that circulating bone marrow derived stem cells promote the regeneration of ischemic tissues. For hematopoietic stem cell transplantation combinatorial granulocyte-colony stimulating factor (G-CSF)/Plerixafor (AMD3100) administration was shown to enhance mobilization of bone marrow derived stem cells compared to G-CSF monotherapy. Here we tested the hypothesis whether combinatorial G-CSF/AMD3100 therapy has beneficial effects in cardiac recovery in a mouse model of myocardial infarction. METHODS: We analyzed the effect of single G-CSF (250 µg/kg/day) and combinatorial G-CSF/AMD3100 (100 µg/kg/day) treatment on cardiac morphology, vascularization, and hemodynamics 28 days after permanent ligation of the left anterior descending artery (LAD). G-CSF treatment started directly after induction of myocardial infarction (MI) for 3 consecutive days followed by a single AMD3100 application on day three after MI in the G-CSF/AMD3100 group. Cell mobilization was assessed by flow cytometry of blood samples drawn from tail vein on day 0, 7, and 14. RESULTS: Peripheral blood analysis 7 days after MI showed enhanced mobilization of white blood cells (WBC) and endothelial progenitor cells (EPC) upon G-CSF and combinatorial G-CSF/AMD3100 treatment. However, single or combinatorial treatment showed no improvement in survival, left ventricular function, and infarction size compared to the saline treated control group 28 days after MI. Furthermore, no differences in histology and vascularization of infarcted hearts could be observed. CONCLUSION: Although the implemented treatment regimen caused no adverse effects, our data show that combinatorial G-CSF/AMD therapy does not promote myocardial regeneration after permanent LAD occlusion.

Hydroxyethyl starch-induced itch: relevance of light microscopic analysis of semi-thin sections and electron microscopy.

BACKGROUND: Hydroxyethyl starch (HES) is widely used as a plasma substitute for improving microcirculation. A major side effect of HES is severe pruritus caused by HES deposits in the skin. Since specific changes are difficult to see in paraffin sections, electron microscopy is the golden standard technique in the diagnosis of HES-induced skin disease. Our aim was to compare electron microscopic search for HES deposits with other techniques. PATIENTS AND METHODS: During the last ten years, we biopsied 21 patients suspected of having HES-induced pruritus. We compared conventional microscopy with hematoxylin & eosin and toluidine blue-stained paraffin sections, toluidine blue-stained glycide ether-embedded, semithin sections and transmission electron microscopy. RESULTS: In 9 patients specific HES deposits could be found by evaluating toluidine blue stained semithin sections by light microscopy alone. In 6 of these cases electron microscopy was also done and confirmed the findings. In contrast, no specific findings due to HES deposits could be detected by conventional histology. CONCLUSIONS: If specific HES deposits are found in toluidine blue-stained, glycide ether-embedded semithin sections, electron microscopy is not required.