Catálogo de publicaciones - libros

The growth of new blood vessels is a critical factor in many human diseases including cancer, ischemic injury and wound healing. De novo vessel formation or vasculogenesis was thought to take place solely in the embryo from mesodermal progenitor cells, whereas the vasculature in postnatal life was considered to undergo remodeling through expansion of pre-existing endothelial cells, or angiogenesis. Current evidence suggests that endothelial progenitor cells (EPCs) also exist in adult organisms as circulating cells originating in the bone marrow. They can be mobilized after vascular trauma, myocardial infarction, tissue injury, or during peripheral vascular disease, by a number of growth factors and chemokines like VEGF, GM-CSF, G-CSF and SDF-1. EPCs do not appear to represent a distinct or homogeneous cell population, but they are defined as cells that can give rise to endothelial progeny under certain circumstances in culture or in vivo. EPCs enhance tissue revascularization by contributing to new vessels and stimulating local angiogenesis, thus offering novel ways to regulate vascular growth. Results from the first clinical studies using mostly bone marrow stem cells as a source of EPCs have been encouraging, emphasizing the therapeutic potential of endothelial progenitor cells. This review summarizes the role of EPCs in the formation of new blood vessels and provides an outline of their biological characteristics and potential use in the clinical setting

The term describes an adhesion molecule family and originates from the integrative function of these molecules between extracellular ligands and the intracellular cytoskeleton (,). Integrins mediate cell-cell, cell-extracellular matrix, and cell-pathogen interactions. Integrins have two major functions: First, they mechanically couple the cytoskeleton to the extracellular matrix or to surface receptors of other cells. Second, they transmit signals from the inside of the cell to the outside of the cell and vice versa (). At least 24 different integrins are known in vertebrates (Fig. 1). Resting platelets express integrins αβ, αβ, αβ, αβ, and αβ (). In addition to these, αβ and αβ expression on activated platelets has been reported ().

Macrophage accumulation is a hallmark of early collateral development and coincides with maximal vascular proliferation and main rise in collateral conductance. Enhancement of macrophage recruitment promoted collateral growth. Yet the precise role of these cells and their origin remained enigmatic. We originally proposed that elevation of shear forces in pre-existing arteriolar anastomoses promotes monocyte homing and macrophage accumulation. Shear force, however, inhibits monocyte recruitment via upregulation of NO and downregulation of cell adhesion molecules. Based upon recent studies we present 2 possible resolutions: 1. Shear forces and expression of NO donating enzymes were initially in collateral arteries allowing recruitment of circulating cells. 2. Furthermore we detected a regenerative subadventitial zone in arterial vessels containing CD 34 positive progenitor cells as main source of macrophages and vascular cells during collateral growth. We thus propose following sequence of events: Hemodynamic changes in preexisting arteriolar shunts lead to activation, proliferation and differentiation of progenitor cells situated in the subadventitial space supplying the cellular components for collateral remodeling. The local pool of progenitor cells is replenished by circulating cells during the very initial phase of collateral growth when due to acute rises in peripheral resistance shear force is lowered. The following remodeling phase of collateral growth occurs in the absence of marked macrophage accumulation and is mainly perpetuated by the differentiation and migration of cells from the existing pool. This new paradigm lowers the importance of acute homing processes and focuses our attention onto local activation of vascular resident progenitor cells as therapeutic target