Multidimensional Proteomics for the Identification of Endothelial Post Mortem Signals of Importance in Vascular Remodeling

Introduction 1.1 Endothelial apoptosis and vascular remodelingAtherosclerotic diseases (AD) and immune-mediated vasculopathy of the transplanted organ (referred to as transplant vasculopathy (TV)) are both characterized by vessel wall thickening and fibrotic changes that lead to progressive vascular obliteration (Al-Lamki et al., 2008;Cailhier et al., 2006;Cornell et al., 2008;Mitchell, 2009;Rahmani et al., 2006;Valantine, 2003).The endothelium, positioned at the interface of blood flow and the vessel wall, serves as a physiological barrier and sensor of environmental stress.The "response to injury hypothesis" proposed by Russell Ross in the 70's suggested that endothelial injury prompts vascular smooth muscle cell (VSMC) migration and proliferation, therefore initiating neointima formation (Ross et al., 1977;Ross and Glomset, 1976).Initially, vascular remodeling is beneficial but repeated cycles of injury, proliferation and repair lead to maladaptive remodeling and lumen narrowing.To date, in vitro and in vivo studies in animals and humans confirmed that endothelial apoptosis is a key determinant in the development of AD and TV (Rossig et al., 2001).Various immune and non-immune factors, such as cytotoxic T-cells, donor-specific antibodies, high cholesterol and hyperglycemia account for increased endothelial apoptosis (Cailhier et al., 2006).In turn, migration and accumulation of VSMC, surviving and accumulating within a hostile environment through acquisition of an anti-apoptotic phenotype, form the initial neointima.Histological and biochemical features characterizing AD and TV include 1) extracellular matrix (ECM) degradation that likely facilitate VSMC migration; 2) acquisition of a synthetic and antiapoptotic phenotype by neointimal cells (VSMC), mesenchymal stem cells (MSC) and fibroblasts associated with Bcl-xl overexpression (Gennaro et al., 2004;Hirata et al., 2000;Pollman et al., 1998) and 3) differentiation of fibroblasts into myofibroblasts of importance in fibrogenic vascular changes (Tomasek et al., 2002) (Figure 1).The molecular interplay regulating intercellular communication between apoptotic endothelial cells (EC) and neointimal cells are only beginning to be unraveled. Proteomics for studying Post Mortem Signals (PMS) exported by apoptotic ECApoptotic programmed cell death is classically considered a silent process.The first clues suggesting that apoptotic endothelial cells may not "go quietly" stems from pharmacological www.intechopen.com How to referenceIn order to correctly reference this scholarly work, feel free to copy and paste the following: Isabelle Sirois, Alexey V. Pshezhetsky

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