Peripheral arterial disease (PAD) represents a spectrum from asymptomatic stenosis to limb-threatening ischemia. The last decade has seen a tremendous increase in the variety of endovascular devices and techniques to treat occlusive disease. Like many evolving technologies, the literature surrounding therapy for endovascular arterial disease consists of mixed-quality manuscripts without clear standardization. Accordingly, critical evaluation of the reported results may be problematic. As such, providers and their patients make treatment decisions without the full benefit of a comparative effectiveness framework. The purpose of this document is to provide a summary for the reporting of endovascular revascularization techniques in the setting of chronic disease. Much of the work in this document is based on prior publications and standards proposed by the Society for Vascular Surgery. We have also made recommendations based on current literature and have attempted to acknowledge shortcomings and areas for future research. The various sections contain summaries of required reporting standards and should serve as a guide for the design of clinical trials and as reference for journal editors and reviewers when considering scientific work pertaining to endovascular therapy for chronic lower extremity arterial disease. An Appendix is provided with commonly used abbreviations in this document.

No abstract

Abstract-We show that 1 of the type II bone morphogenetic protein (BMP) receptor ligands, BMP4, is widely expressed in the adult mouse lung and is upregulated in hypoxia-induced pulmonary hypertension (PH). Furthermore, heterozygous null Bmp4 lacZ/ϩ mice are protected from the development of hypoxia-induced PH, vascular smooth muscle cell proliferation, and vascular remodeling. This is associated with a reduction in hypoxia-induced Smad1/5/8 phosphorylation and Id1 expression in the pulmonary vasculature. In addition, pulmonary microvascular endothelial cells secrete BMP4 in response to hypoxia and promote proliferation and migration of vascular smooth muscle cells in a BMP4-dependent fashion. These findings indicate that BMP4 plays a dominant role in regulating BMP signaling in the hypoxic pulmonary vasculature and suggest that endothelium-derived BMP4 plays a direct, paracrine role in promoting smooth muscle proliferation and remodeling in hypoxic PH. Key Words: bone morphogenetic proteins Ⅲ endothelial cells Ⅲ hypoxic pulmonary hypertension Ⅲ signaling pathways Ⅲ Smad Ⅲ vascular remodeling Ⅲ vascular smooth muscle cell proliferation C hronic hypoxia is the most common underlying cause of secondary pulmonary hypertension (PH) in humans. 1 This is associated with the development of fixed defects in the pulmonary vasculature, including medial wall thickening and muscularization of the peripheral vasculature, both mimicked by a rodent model of hypoxic PH in rats and mice. 2,3 Numerous studies using these experimental models provide evidence of an imbalance in the secretion of vasoactive agents and mitogens in the pulmonary vasculature, leading to structural changes in the pulmonary vasculature. 4 -6 Genetic studies in patients with familial primary pulmonary hypertension (FPPH) have identified mutations in 1 of the 3 known type II bone morphogenetic protein receptors (BMP-RII), BMPR2. 7-9 BMP-RII is a member of the transforming growth factor type ␤ family of receptors that acts downstream of the BMP family of ligands. 10,11 BMP ligands interact with 2 classes of transmembrane receptors, termed type I receptors, (ALK2, 3, and 6), and the type II receptors (BMP-RII and Act-RIIA and -IIB). Ligand binding induces type I-receptor phosphorylation by type II receptors, leading to activation of downstream signaling including the classical Smad1/5/8 and the alternative p38 and extracellular signalregulated kinase, mitogen-activated protein kinase, phosphatidylinositol 3-kinase, and protein kinase C pathways. 10,11 Evidence of a role for this signaling pathway in hypoxic PH was shown in 2 recent in vivo studies. By manipulating BMP-RII signaling through 2 different approaches, these studies demonstrated that BMP-RII can promote opposite effects on the pulmonary vasculature under different conditions. 12,13 To explore the mechanisms mediating these effects, we looked at the regulation BMP ligands and downstream signaling in a mouse model of hypoxia-induced PH. One of these ligands, BMP4, is widely expressed in the adult...

No abstract

Current strategies for skeletal regeneration often require co-delivery of scaffold technologies, growth factors, and cellular material. However, isolation and expansion of stem cells can be time consuming, costly, and requires an additional procedure for harvest. Further, the introduction of supraphysiologic doses of growth factors may result in untoward clinical side effects, warranting pursuit of alternative methods for stimulating osteogenesis. In this work, we describe a nanoparticulate mineralized collagen glycosaminoglycan scaffold that induces healing of critical-sized rabbit cranial defects without addition of expanded stem cells or exogenous growth factors. We demonstrate that the mechanism of osteogenic induction corresponds to an increase in canonical BMP receptor signalling secondary to autogenous production of BMP-2 and −9 early and BMP-4 later during differentiation. Thus, nanoparticulate mineralized collagen glycosaminoglycan scaffolds may provide a novel growth factor-free and ex vivo progenitor cell culture-free implantable method for bone regeneration.